Binary CuO-P2O5 glasses were not durable enough for use as high touch point articles, so Fe2O3 was added to the compositions to increase the chemical durability. The amount of Cu leachate decreased by at least 3 orders of magnitude when Fe2O3 was increased from 0 to 13.1 mol%. At the highest Fe2O3 contents and corresponding highest durability, the glass was no longer able to pass a test of antimicrobial efficacy with < 3 log kill compared to > 5 log kill for all other compositions. Ab-initio molecular dynamics simulations showed increasing bridging oxygen species at the expense of non-bridging oxygen species with the increase in Fe2O3 content, showing that the glasses exhibited increased chemical durability because they were more interconnected and structurally bound. Experimental results with glasses at fixed CuO and decreasing Fe2O3 confirmed that Fe2O3 content (not CuO) controlled the Cu release rate and, thus, the antimicrobial efficacy of the glasses. The significance of the oxidation state of the leached Cu was overwhelmed by the importance of the amount of Cu leachate.Glasses with high antimicrobial efficacy were developed in the Fe Fomite transmission is of particular concern for nosocomial infections, as compliance with hand hygiene practices (the primary infection control method) is typically only 40–50% in health care settings8. Due to the significant risks of fomite-mediated transmission, there is a need for materials that possess antimicrobial (AM) and antiviral (AV) properties to reduce this transmission pathway.The COVID-19 pandemic emphasized that infectious disease outbreaks can have a significant effect on global health and the economy. While COVID-19 is primarily transmitted through respiratory droplets2O3-CuO-P2O5 glasses (hereafter referred to as FeCuP glasses) were investigated. Optimized compositions exhibited comparable antimicrobial efficacy to Cu metal in a modified version of the Method for the Evaluation of Antimicrobial Activity of Hard, Nonporous Copper-Containing Surface Products9. The FeCuP glasses are phosphate glasses  simulations and leaching experiments, it was found that increasing Fe2O3 contents increased the glass polymerization such that above a certain threshold, not enough Cu was released to exhibit high AM efficacy. Cu redox was also found to contribute to AM efficacy, though the oxidation state of the Cu was not as important as the total amount of Cu released from the surface of the glass. In this study, six glasses were investigated to understand the AM behavior in the FeCuP system as a function of composition. These compositions fall within one of the very few areas of composition space that have exhibited > 5 log reduction in antimicrobial testing, so identifying the mechanism driving the AM behavior will help with composition optimization as well as with future AM material design.The most important property of these glasses is chemical durability. Compositions with insufficient durability reacted with ambient moisture and dissolved, resulting in poor reliability for use as high touch point articles. If the glasses were too durable, then Cu could not leach from the surface, resulting in poor antimicrobial efficacy. This study varied the chemical durability of the glasses by changing the glass composition . Using 2O3 content increased in increments of 5 mol% at the expense of CuO while batched P2O5 was held constant at 45 mol%. In the fourth, fifth, and sixth compositions (Series B), batched CuO was held constant at 40 mol%, and batched Fe2O3 decreased by 2.5 mol% with increasing P2O5. The analyzed compositions (Table 2. Compositions shown in Table 2 (0.3–1.3 mol%). The AIMD simulations were based on the renormalized, analyzed compositions coupled with the measured oxidation state data. Values used for the AIMD simulations are reported in Supplementary Table 2) are included in Supplementary Table Six glass compositions were investigated Table , Fig. 1.4(PO4)2O and CuFeO2 10. Five of the six glasses exhibited high antimicrobial efficacy, with > 5 log kill of the Staphylococcus aureus bacteria that were spread onto the glass coupon surface and incubated for 120 min under ambient laboratory conditions  are single phase amorphous materials with high Cu contents. The primary mechanism of antimicrobial efficacy is the presence and release of Cu ions from the glass surface, where the effectiveness of the Cu decreases with increasing oxidation state Cu0 > Cu+ > Cu2+12O3 in the glass, the amount of leached Cu decreased linearly on a log scale  after each day, where the DI water was sampled and replaced every day for five days. With increasing Fe2O3 leached the least Cu on days 1, 2, and 3 , the glass compositions with the highest FeFigure When the ratios of the leached atoms were compared to the initial atomic ratios in the glasses, it was shown that the glasses dissolved incongruently , however, was the lone composition that showed low AM efficacy. As mentioned above, this composition leached the least amount of Cu  followed by Cuy glass #, howeverAb-initio molecular dynamics simulations were performed using modified versions of the renormalized, analyzed glass compositions which were corrected to account for the oxidation states of the Cu and Fe. For glasses #2, #3, #5, and #6, too many atoms were required to model the system containing P2O5, Cu2O, CuO, FeO, and Fe2O3 . To simplify those compositions, all Fe was accounted for as FeO instead of as FeO and Fe2O3 as there was < 3 mol% Fe2O3 in each of the glasses. Glass #4 was used to test the hypothesis that treating all Fe as FeO would not change the glass structures within the uncertainty of the simulation results. For all bond types present at fractions larger than 1.3% , there was a difference of < 3.2% between the case where the simulations were run with all five oxide components compared to when they were run with only four oxide components  and decreasing Fe2O3 at the expense of P2O5 (Series B).2O3 and more P2O5 than was obtained in the experiments , more and more P–O–Fe, Fe–O–Fe, and P–O– bridging oxygen bonds formed at the expense of the non-bridging P–O–x bonds . The edge sharing comes from FeO6–FeO6 polyhedron and was observed at the expense of corner sharing, which was 100% in the glass that did not contain Fe2O3. Overall, the introduction of Fe2O3 and the increase in Fe2O3 in the Series A and Series B glasses resulted in the creation of FeO6 octahedra and an increase in bridging oxygens.Figure lue Fig. . With in2O3 was used to increase the glass’ chemical durability. Fe2O3 is known to increase the chemical durability of phosphate glasses and has long been used in glasses designed for high-level, radioactive nuclear waste encapsulation12.While copper phosphate glasses exhibit high AM efficacy, they react with ambient moisture and dissolve forming a Cu-infused, phosphoric acid gel. Such surface reaction and dissolution is not practical for high touch-point articles, so Fe2O3 threshold above which there would no longer be sufficient Cu release from the surface for the glasses to exhibit high AM efficacy (where high AM efficacy is defined as log kill ≥ 3). At elevated Fe2O3 content , the glass became so durable that Cu could not be easily leached from the surface, and the glass exhibited low AM efficacy. Because the increase in Fe2O3 in Series A was accompanied by a decrease in CuO , Series B was designed to test whether high AM efficacy could be achieved at the lowest CuO content by reducing the Fe2O3 content in the glass. In both glasses #5 and #6, the durability decreased with the decrease in Fe2O3, and the glasses exhibited high AM efficacy despite containing the lowest total CuO. Combined, these two series of glasses showed that the chemical durability of the glasses in the FeCuP system can be controlled by the Fe2O3 content of the glass, such that the log of the leached Cu, P, and Fe decreased linearly with increasing Fe2O3 , P–O–Fe, and Fe–O–Fe bonds. This is supported by the AIMD simulations and the fitted data from Mössbauer spectroscopy  strengthen the bonding of the ends of the chains to the surrounding glass12, and/or (3) replace P–O–P bonds with more hydration-resistant P–O–Fe bonds18. In this study, most of the hydration-resistant bonds formed at the expense of the non-bridging oxygen P–O–x bonds, not the P–O–P bonds  that Fe was strengthening the bonding at the end of the chains by reducing the number of non-bridging oxygens. This behavior is also consistent with similar structural behavior observed by a wide body of research into transition metal phosphate glasses, with potential applications ranging from biomedical to nuclear waste immobilization19. The experimental and modeling results suggest that the increase in chemical durability was caused by a more interconnected and bound glass structure at higher Fe2O3 contents. Between 9.1 and 13.1 mol% Fe2O3, there was a threshold above which the FeCuP glass structure was too structurally bound to release enough Cu to exhibit high AM efficacy.For the glasses discussed here, the Fends Fig. , suggest0), then becomes less effective at killing bacteria and viruses with increasing oxidation state (Cu0 > Cu1+ > Cu2+)10. Cu1+/Total Cu was determined for all six glasses. Glass #4, the only composition that showed low AM efficacy, had the highest Cu1+/Total Cu ratio and the most moles of Cu1+  in glass #4 caused the increased polymerization of the network, resulting in the low leach rates. So, while glass #4 had the lowest total CuO content in Series A, it was the high Fe2O3 content that prevented the glass from achieving high AM efficacy. These conclusions highlight that although Cu redox was a contributing factor to the AM efficacy of the FeCuP glasses, the contribution of Cu redox to AM efficacy was overwhelmed by the amount of released Cu. This was seen in glasses #1, #2, #3, #5, and #6, which contained more oxidized Cu but released more of it  from redox cycling between the three oxidation states of Cu24. The third mechanism is DNA degradation, where some studies have observed cell membrane deterioration followed by DNA degradation25. Regardless of which of these mechanisms (or which combination of them) is occurring in the FeCuP glasses, many of these studies have found that the amount of Cu release is critical for determining AM efficacy, similar to the findings presented here28.The first mechanism that is often described is cell membrane damage and subsequent cell death caused by Cu ions released from the matrix of the contact material. For 2O3-CuO-P2O5 system for the first time. Chemical durability was the most critical glass property as it determined both the amount of Cu release  as well as whether the glasses would react and dissolve under ambient conditions. To increase the chemical durability, Fe2O3 was added to the glasses. Higher Fe2O3 contents resulted in higher chemical durability such that the highest Fe2O3 content glass was so durable that not enough Cu was released to achieve ≥ 3 log kill in the test of antimicrobial efficacy. It was found that Fe2O3 increased the bridging oxygen species in these glasses at the expense of the non-bridging oxygen species. This increased the polymerization of the glasses and prevented dissolution. Cu redox was not as important a parameter as the total amount of leached Cu for AM efficacy, where the Fe2O3 content determined the total amount of Cu release for the glasses in this study. In summary, FeCuP glasses were described, and the relationship between glass composition, glass structure, and antimicrobial efficacy was explored.This paper discussed black, antimicrobial glasses in the Fe4H2PO4; BassTech), iron (III) phosphate , and cupric oxide . Raw materials were mixed in a Turbula® mixer for 45 min, then calcined overnight at 250 °C in a 650-cc fused quartz crucible with a refractory silica lid. Glasses were melted at 850 °C for 1 h, then 1100 °C for 30 min in the fused quartz crucible with the lid. Glasses were then poured into graphite molds that were pre-heated to 350 °C. The top, exposed surfaces of the glasses were immediately placed in an inert Ar atmosphere. The Ar flowed above the top of each glass and another heated mold was placed on top to create a sealed environment. Once the surface of the glass was quenched, the Ar gas was turned off, and the glass was allowed to slow cool in the graphite molds. The resulting cast disks were 152.4 mm in diameter, ~ 12.7 mm thick, and had a glossy black appearance on the top surface. The inert atmosphere was critical for preventing a thin layer of surface crystallization from reaction with oxygen. The glasses had very low annealing temperatures, so slow cooling the glasses in the molds relieved thermal stresses, and a subsequent annealing step was not required.Glasses were prepared using ammonium dihydrogen phosphate , 4 mL of 1:1 hydrochloric acid (HCl), and 1 mL of hydrofluoric acid (HF). The solution was then placed in a hot block until the digestion was completed (~ 2–8 h). After digestion, the solution was transferred to a 500 mL flask containing 10 mL of nitric and hydrochloric acids such that the final acid concentrations were approximately 2% HNO3, 2% HCl, and 0.2% HF. Each sample solution was then analyzed using a Perkin Elmer Optima 7300V Simultaneous ICP-OES with a matrix-matched standard and blank to determine the concentrations of Fe, Cu, P, and Si.The chemical compositions of the glasses were measured using inductively coupled plasma-optical emission spectroscopy (ICP-OES). A 0.05 g portion of each sample was weighed and placed in a Digitube bottle, followed by 5 mL of deionized (DI) water, 4 mL of 1:1 nitric acid  were identified using a combination of the Jade search match and the ICDD’s PDF-4 manual search.9. Each glass coupon was tested in duplicate. A 20-µL aliquot of thawed Staphylococcus aureus bacterial cultures was added to 10 mL Tryptic Soy Broth (Teknova). These bacterial suspensions were incubated at 36 °C for 18–24 h. The suspension was then centrifuged at 5000 rpm for 10 min, after which the supernatant was removed, and the pellet was re-suspended in 5 mL of 1X phosphate buffered saline. An organic soil load containing 0.25 mL of 5% fetal bovine serum (Gibco Life Technologies) and 0.05 mL Triton X-100 (Amresco Pro Pure) was added to 4.70 mL bacterial suspension to aid in spreading the inoculum. The optical density of the inoculum was recorded.Bactericidal efficacy tests were conducted using a modified version of the U.S. E.P.A. Method for the Evaluation of Antimicrobial Activity of Hard, Nonporous Copper-Containing Surface ProductsEach coupon was inoculated with 20 µL of the bacterial test culture. The inoculum volume was spread evenly using bent sterile pipette tips (Mettler-Toledo) to ensure full and even coverage, spreading as close to the edge of the coupon as possible. Coupons were then incubated under ambient laboratory conditions for a period of 120 min. Following the 120 min exposure period, coupons were neutralized in 20 mL Letheen broth (Hardy Diagnostics). Ten-fold serial dilutions of the neutralized solutions were plated using standard spread plate technique on Tryptic Soy Agar plates and incubated for 24 or 48 h at 36 °C to yield countable numbers of survivors (approximately 20–200 colonies per plate).Leach testing was conducted on two separate coupons for glasses #3, #4, and #6 and on a single coupon tested for other compositions. The limited number of test coupons available was due to the desire to conduct all experiments and measurements on glass from the same melt pour to keep the redox state of the Cu and Fe in the glass consistent across measurements and tests. Each coupon was submerged in 15 mL DI water in a covered container and leached for a total of 5 days at ambient temperature. On days 1, 2, 3, 4, and 5, the entire 15 mL volume was removed for analysis, the coupon briefly rinsed with deionized water, and again submerged in 15 mL of fresh DI water. When multiple coupons were tested, the leachate was analyzed separately rather than combined into a single aliquot, and error bars are shown as the standard deviation of the two measurements. Testing was not extended past five days due to the significant decrease in the leached elements. Leachate was analyzed using an Agilent 7700s ICP-MS with results reported for Fe, Cu, and P.2+/total Fe ratio.The glasses in this study contained the following multivalent species: only Cu or Cu and Fe. The redox states of the Cu and Fe were measured using a combination of inductively coupled plasma–optical emission spectroscopy (ICP–OES) to determine the total Cu and Fe contents and Cr/Cu and Cr/Fe redox reactions to determine total reducing power of the glass. Mössbauer spectroscopy was used to measure the Fe2SO4, 5 mL HF, and ~ 90 mL H2O). To determine the total reducing power of glasses #5 and #6, 0.05 g of ground sample was dissolved in the same diluted acids. For all the glasses, a known amount of Cr6+ was added to the solutions in the form of K2Cr2O7. The amounts added were expected to oxidize any reduced species and provide a small excess. Upon the addition of the Cr6+, the following two reactions occurred if both Cu and Fe were present, and only reaction  was determined using the redox reaction and titration described above , and the total available reducing power of multivalent species (denominator) was determined using the measured ICP–OES data. The total available reducing power assumes that all the Fe and Cu are present in their reduced forms. Total reducing power can vary between 0 and 1, where 0 means that there are no reduced species present, and 1 means that there are no oxidized species present.2+/Total Fe ratio, then the Cu1+/Total Cu was calculated.For glasses #2–#6, Mössbauer spectroscopy was used to determine the Fe57Fe Mössbauer spectroscopy measurements utilized acrylic absorber discs with a sample area of 1.767 cm2. The disks were loaded to present 2.16 × 10−3 g cm−2 of Fe and achieve a Mössbauer thickness of 130. Samples were homogeneously mixed with graphite to achieve this level of loading. The 14.4 keV γ-rays were supplied by the cascade decay of 25 mCi 57Co in a Rh matrix source and were oscillated at constant acceleration. All measurements were calibrated relative to α-Fe foil. Spectral data were fitted using the Recoil software package31 using a Voigt-based fitting approach32. The fitted areas for individual doublet components enabled an estimation of the Fe2+/Total Fe ratio. However, as noted in previous publications, the recoil-free fraction ratio, f(Fe3+)/f(Fe2+), which is often assumed to have a value of 1 for oxide glasses, is 1.3 for other phosphate glasses which are compositionally very broadly similar to the glasses studied here16. Consequently, the estimations of redox ratios here assume that f(Fe3+)/f(Fe2+) = 1.3 (Supplementary Table ab-initio molecular dynamics (AIMD) was adopted. Initially, the atomic elements for a specific composition were randomly distributed in a fixed volume box and heated to a temperature of 4000 K for 5 ps (NVT) to mimic experimental melting process. The system was then subjected to a quenching cycle to rapidly cool it down to 300 K for 30 ps. At 300 K, the system was equilibrated for additional 2.5 ps, followed by a final optimization step of constant energy (NVE) run for 2.5 ps to achieve an equilibrium atomic bonding arrangement. To ensure the accuracy of the results, 5 structures were generated for a given composition and were analyzed to obtain a static set of properties. This methodology has been successfully employed in previous studies to predict both structural and electronic properties. More detailed methodology can be found in a previous report33.To generate glass structures of each composition, Vienna ab-initio simulation package (VASP)35, and the generalized gradient approximation (GGA) was used for the exchange–correlation functional36. A cutoff energy was set as 430 eV with single point k-mesh, and core electrons were incorporated with pseudopotentials with the projector augmented wave (PAW) method37.AIMD calculations were performed with the The number of atoms needed to represent each glass system in the AIMD simulations was determined from the mol% values. The total number of atoms was reduced by dividing by the highest common denominator . This division resulted in preserving the ratio of the atoms while lowering the total number of atoms. To keep the total number of atoms in the system close to 200, the glass #1 composition and the simplified compositions were then multiplied by 2. The 200-atom system was chosen to obtain the most information with reasonable computation times using AIMD and with the expectation that the model would converge. There was no additional modification to the ‘not simplified’ case for glass #4. Modeled compositions are shown in Supplementary Table Supplementary Information.


A survey of known compounds shows that tilt systems with both out-of-phase ϕ-tilts about the  n = 1 Ruddlesden–Popper (RP) structure. The crystal structures of compounds belonging to this family are compared with the predictions of the symmetry analysis. Approximately 88% of the 140 unique structures have symmetries that agree with those expected based on octahedral tilting alone, while the remaining compounds have additional structural features that further lower the symmetry, such as asymmetric packing of bulky organic cations, distortions of metal-centered octahedra or a shift of the inorganic layers that deviates from the a/2 + b/2 shift associated with the RP structure. The structures of real compounds are heterogeneously distributed amongst the various tilt systems, with only 9 of the 47 tilt systems represented. No examples of in-phase ψ-tilts about the a and/or b axes of the undistorted parent structure were found, while at the other extreme ∼66% of the known structures possess a combination of out-of-phase ϕ-tilts about the a and/or b axes and θ-tilts (rotations) about the c axis. The latter combination leads to favorable hydrogen bonding interactions that accommodate the chemically inequivalent halide ions within the inorganic layers. In some compounds, primarily those that contain either Pb2+ or Sn2+, favorable hydrogen bonding interactions can also be achieved by distortions of the octahedra in combination with θ-tilts.A symmetry mode analysis yields 47 symmetrically distinct patterns of octahedral tilting in hybrid organic–inorganic layered perovskites that adopt the  Amongst all-inorganic compositions with layers one octahedron thick, RP phases have twice as many large ‘A-site’ cations as octahedra, giving a stoichiometry of A2BX4, whereas the DJ phases have a stoichiometry of ABX4. However, in hybrid phases, the patterns of layer stacking are such that it is not always possible to classify compounds as belonging to the DJ or RP families from their composition alone. The structural implications of layer-stacking patterns, including layer shifts intermediate between the DJ and RP phases, are discussed at length in a recent paper by McNulty & Lightfoot  family, where the inorganic layers stack in such a way that the octahedra line up on top of one another when viewed perpendicular to the layers , even though octahedral tilting distortions appear to be ubiquitous amongst these compounds . The results for tilts/rotations perpendicular to the layers (θ-tilts) and/or out-of-phase tilts within the layers (ϕ-tilts) largely agree with the earlier analysis of Hatch et al.  rather than cubic (Pm3m), the symmetry consequences of tilting about the c axis are different than tilting about the a and b axes. More importantly, the offset of a/2 + b/2 from one layer to the next means that the octahedra in adjacent layers are not aligned on top of one another and therefore one cannot speak of in-phase or out-of-phase tilting about the c axis, at least not for n = 1 RP phases. For these reasons the notation developed by Alexandrov is used throughout this paper.There are two notations for describing octahedral tilting in perovskites, one developed by Glazer 1972 and the a) shows an undistorted inorganic layer from a hybrid n = 1 RP phase. Rotations of the octahedra about the c axis of the tetragonal parent structure are denoted by the Greek letter θ and are illustrated in Fig. 2b). Rotations about the a and/or b axes can be either in-phase or out-of-phase and are represented by the Greek letters ψ and ϕ, respectively. Fig. 2c) illustrates in-phase ψ-tilts around the b axis, denoted (0ψ0). Simultaneous ψ tilts around both a and b are also possible, as illustrated by the (ψψ0) tilt system in Fig. 2d). If there are tilts about two axes, but of different magnitudes, subscripts are used to signify their inequivalence (ψ1ψ20). The same convention is used to describe out-of-phase ϕ-tilts. Examples of layers with (0ϕ0) and (ϕϕ0) tilting are illustrated in Figs. 2e) and 2f), respectively.Fig. 2Because the octahedra in different layers are not connected, the tilting pattern in a given layer is, in principle, independent of the tilting in neighboring layers. To account for this, the tilting in each layer must be specified, for example, (ϕ00) tilting in layer 1 and (ϕϕθ) tilting in layer 2 would be written as (ϕ00)/(ϕϕθ). More complicated schemes where more than two layers are needed to capture the periodicity of the tilts are uncommon and therefore not considered in this analysis. In practice, the tilts are generally the same from one layer to the next; however, the directions of the tilts can differ from layer to layer, and this can have symmetry consequences, as discussed below.I4/mmm cell in one layer to the octahedron at the body center in the next layer. If these two octahedra tilt in the opposite direction it is written as either To compare the direction of tilting in alternating layers, we compare the octahedron at the origin of the parent 3.A2BX4 crystal structure through a direct crystallographic approach ]. The subgroups determined by ISODISTORT were visualized with the ISOVIZ application which allowed the respective tilting scheme to be identified by visual inspection. The symmetry analysis was limited to structural distortion modes that can be described as rotations of the Ni-centered octahedra. Note that because hybrid layered perovskites with the DJ structure have a different parent structure, one with P4/mmm space group symmetry, the results of our analysis do not apply to DJ compounds or to compounds with layer shifts intermediate between RP and DJ phases. Interested readers are directed to earlier works by Aleksandrov et al. ,  and  for X, N and P, respectively. The irreps are labeled with respect to the I4/mmm parent cell of the RP structure as depicted in Fig. 1b). The symbols follow the notation of Miller & Love  or lost (−). The distortions associated with the N and P irreps correspond to complex patterns of octahedral tilting that require more than two layers before repeating. With the exception of the P4 irrep, these types of octahedral tilting are rarely encountered, and therefore are not investigated further here. The P4 irrep produces a complex pattern of θ-tilts that repeats every four layers and leads to I41/acd space group symmetry. As noted by Balachandran et al. , must be included as one arm of the X k-point with a = 1/2.Hatch  al. 1989 previousLove 1967, where t al. 2014, this disupporting information. The θ tilts can be described as rotations about the fourfold axes that run parallel to the c axis of the parent cell. The ψ tilts are in-phase rotations about axes that run parallel to either the a or the b axis of the parent cell, and the ϕ tilts are out-of-phase rotations about the axes that run along the face diagonals of the parent cell, either [110] or [110]. Though Four irreps are found to be responsible for the tilts discussed in the previous section: g. The order parameter identifies the invariant subspace containing all distortion vectors that possess the related distortion symmetry. Since the g1 and g2) are associated with each irrep. For c axis of the parent cell). When the order parameter is  the octahedra in layers 1 and 2 rotate by the same magnitude, but the octahedron at the origin and the octahedron at the body center rotate in the opposite sense so that the tilt system is (00θ)/ the rotations cancel in one layer and add in the second layer, giving the tilt system (000)/(00θ). When the magnitudes of the two order parameters are different  they produce rotations of different magnitudes in layers 1 and 2, giving the tilt system (00θ1)/(00θ2). From a symmetry perspective, the tilt system (00θ)/(00θ) is a special case of (00θ1)/(00θ2). In this structure, which has orthorhombic Pbam symmetry, there is no symmetry element that forces the rotations in one layer to be equal to those in the layers above and below. This finding differs from the earlier work of Hatch et al.  the tilts are about [110] in each layer. For a) this leads to the (ϕϕ0)/(ϕϕ0) tilt system, while for the a, a) represents tilts about axes that run along either [110] or [110]. The net effect of this combination is a tilt about [100] in the first layer and [010] in the second layer, leading to the tilt system (ϕ00)/(0ϕ0) for a, b) the tilt systems that result are (ϕ1ϕ20)/(ϕ2ϕ10) and (ϕ1ϕ20)/(210) for As mentioned previously, the et al. (19891ϕ2θ)/(2ϕ1θ) should be classified as (ϕ1ϕ2θ)/(21θ) as shown in Fig. S2.The results of our analysis for θ tilts, ϕ tilts and combinations of the two are given in Table 1 al. 1989, but thea and b axes in the first layer and two about the same axes in the second layer. An additional five tilt systems that involve a combination of ψ-, ϕ- and θ-tilts are given in Table S1 of the supporting information. One interesting result from this study is that distortions involving ψ-tilts can produce noncentrosymmetric and polar space groups, whereas distortions involving only θ and ϕ tilts invariably result in centrosymmetric space groups. In retrospect, this result might have been anticipated from the fact that the The symmetry analysis for in-phase ψ tilts described by the SM3 irrep, as well as those that result from the coupling of the SM3 and the 4.n = 1 RP structure and classify their patterns of octahedral tilting. The tilt systems were determined by visual inspection of the reported crystal structures using the VESTA3 software  and Cambridge Structural Database (CSD) were surveyed to find halide variants of the 4+ are grouped with the inorganic phases because NH4+ is a spherical cation with no torsional degrees of freedom, and as such behaves more like an alkali cation than an organic cation  distortion, either Cu2+ or Cr2+. A symmetry mode analysis of cooperative JT distortions in K2NiF4 compositions shows three symmetrically distinct patterns of distortion. If the elongated axis of the octahedron is oriented perpendicular to the layers the symmetry remains I4/mmm, but if the elongated axis is located within the layers the symmetry can be either Cmce or Pbam, depending on the directions of the distortions from one layer to the next. Interestingly, these two types of cooperative JT distortion are equivalent by symmetry to (00θ)//2MgF4. The former retains the undistorted I4/mmm structure down to 4 K, but the latter has P21/c symmetry with the tilting scheme (ϕ1ϕ2θ)/. The compounds containing NH al. 2014 found thA2BX4 stoichiometry and either Cl–, Br– or I– as the anion. The list can be culled down to 140 unique structures by eliminating: (1) isostructural entries with the same composition, (2) entries that have .cif files with flags that call into question their accuracy and (3) entries where the offset between layers differs from the a/2 + b/2 characteristic of the RP structure. The first criterion ensures that entries originating from variable-temperature studies where the same structure is observed at multiple different temperatures are counted only once. The second criterion culls questionable structure determinations. The third criterion eliminates entries that adopt the DJ structure or a structure that is intermediate between the RP and DJ structures. This is important because if the layer shift factor differs from a/2 + b/2 the symmetry of the parent space group is typically altered //(ϕϕn = 1 DJ phases with this symmetry in their recent review. This is in contrast with tilt system (ϕϕθ)/(ϕϕθ), which leads to Pbca symmetry, where any deviation of the layer shift factor from a/2 + b/2 alters the symmetry. Entries removed due to irregular layer shifts tend to be most prevalent in compounds that have large and/or bulky organic cations. Details of the survey can be found in Tables S3 and S4.A survey of hybrid compounds with organic cations separating the inorganic layers paints a very different picture. A search of both the CSD and ICSD revealed approximately 200 entries corresponding to layered hybrid organic–inorganic compounds with l. 1987b showed tfoot 2021 found maTable 3T > 340 K) and then only for six compounds. This finding is not too surprising as the cavities where the organic cations reside in the parent structure contain a fourfold axis and two mirror planes (point symmetry 4mm or Cv4), a combination of symmetry elements not found in any organic cation among the hybrid compounds surveyed. To realize the symmetry of the undistorted parent structure the position of the organic cation must be disordered, and dynamic motions favored at high temperatures are the most likely source of this disorder. If there were more high-temperature structural studies there might be more examples of the parent structure, though in many cases decomposition would likely occur before a temperature is reached where the I4/mmm parent structure is stabilized.The first thing to note is that, unlike their all-inorganic counterparts, the undistorted structure is only observed at high temperatures (P21/c symmetry and (ϕϕθ)/(ϕϕθ) with orthorhombic Pbca symmetry are the most common. In fact, tilt systems involving both ϕ- and θ-tilts account for ∼66% of the entries. There are seven examples of (ϕ1ϕ2θ)/(ϕ1ϕ2P21/c associated with (ϕϕθ)/(ϕϕP1 associated with (ϕ1ϕ2θ)/// leaving only ϕ-tilts.It is also important to recognize that many compounds undergo changes in tilt system as a function of temperature. As such, temperature becomes an important variable when assessing the stabilities of competing tilt systems. Among compositions that contain divalent manganese, iron or cadmium it is common to observe both ϕ- and θ-tilts at low temperatures, but as the temperature increases the θ-tilts are lost  between organic cations, and hydrogen bonding between the organic cations and inorganic layers. The lack of octahedral tilting distortions in all-inorganic n = 1 RP phases suggests that bonding interactions within the inorganic layers are not the driving force behind octahedral tilting. Any impact of octahedral tilting on the packing of the organic cations would be a second-order effect. Therefore, we can assume that octahedral tilting distortions are largely driven by hydrogen bonding interactions between the ammonium head groups of the organic cations and the halide ions of the inorganic layer.The structure-directing forces that are operative in hybrid A-site cation sits on a site with 4mm (Cv4) symmetry. It is surrounded by four terminal halide ions and four bridging halide ions. The presence of eight halide ions around the –NH3+ head group of the organic cation is not optimal for forming strong hydrogen bonds. Octahedral tilting distortions lower the symmetry, allowing some halide ions to move toward the ammonium head group while others move away. Tilt systems that create an environment where each hydrogen on the –NH3+ can form a strong hydrogen bond with a single halide ion will presumably be the most favorable.In the undistorted parent structure, the A-site cation and all four terminal halides move away from the A-site cation. For the sites shaded in pink, the halide ions move in the opposite sense. Thus, we see that ψ-tilts create inequivalent environments for the organic cations, a violation of Pauling’s rule of parsimony  layer. It is common to all tilt systems with in-phase ψ-tilts. Fig. 2d) shows that this effect is even more pronounced for a layer with (ψψ0) tilting. A similar feature is known for 3D perovskites, where in-phase tilts about two or more axes lead to chemically inequivalent A-sites. In 3D perovskites, these patterns of tilting can generally only be stabilized by using A-site cations of different sizes and bonding preferences  preserves the 12-fold coordination of the Ca2+ ion while the smaller Cu2+ ion adopts a fourfold square planar coordination environment PbI4 and PbBr4 – albeit with a 1/2a + 0b layer shift that is intermediate between an RP and a DJ phase 2CdCl4 is illustrative. Not only does the small size of the methylammonium cation minimize dispersion forces within the organic layer, but this compound also adopts three different tilt systems as a function of temperature: (ϕϕθ)/2CdCl4 we need to consider the hydrogen bonding interactions more carefully. Let us begin by putting the H—Cl distances and N—H—Cl angles into context. Steiner  = 2/3, and the terminal halide ion is assigned 1 × (1/3) = 1/3 of its expected valence from bonding to cadmium. The unfulfilled bonding must come from hydrogen bonds. In practice, the terminal Cd—Cl bonds are somewhat shorter [2.537 (4) Å] than the terminal Cd—Cl bonds [2.644 (3) Å] at 295 K, but that does not invalidate the notion that the terminal chlorides must form either stronger or more numerous hydrogen bonds than the bridging chlorides.n = 1 hybrid RP phases , where the terminal halides are found to have bond valence sums ranging from 0.36 to 0.44, and the bridging halides values ranging from 0.71 to 0.85.We can be more quantitative if we calculate bond valence sums from the experimentally observed Cd—Cl bond distances /(ϕϕ0) tilting. Examples are found for n = 1 RP phases with iron and manganese as well. However, in those cases where diffraction studies have been carried out at low temperatures, the (ϕϕ0)/(ϕϕ0) pattern usually transforms to a tilt system with both ϕ- and θ-tilting on cooling. Also note that for organic cations larger than methylammonium (CH3NH3+) the symmetry elements associated with (ϕϕ0)/(ϕϕ0) tilting lead to disorder in the positions of the hydrocarbon part of the organic cation. Presumably, the configurations and/or orientations of the organic cation are dynamic at high temperatures and couple to dynamic θ-tilts of the inorganic layer. At low temperatures these lattice vibrations freeze out, leading to a transition into a tilt system with both ϕ- and θ-tilts.Of the tilt systems observed in real compounds only (ϕϕ0)/(ϕϕ0) leads to the less favorable bridging configuration. Yet there are no fewer than seven different P21/c symmetry and (ϕϕθ)/(ϕϕθ) which leads to orthorhombic Pbca symmetry. Because the tilting in any one layer is of the (ϕϕθ) type in both tilt systems, very similar patterns of hydrogen bonding emerge. However, the alternation in the direction of the θ-tilts observed in the Pbca structure will lead to slightly different orientations of the organic cations than those observed in the P21/c structure. This suggests that dispersion forces between organic cations play a key role in the competition between these two tilt systems. Evidence to support this hypothesis can be found among the behavior of n = 1 lead iodide RP phases containing linear alkyl ammonium cations, [H(CH2)nNH3]2PbI4 / show the opposite behavior (ϕϕθ)/(ϕϕθ) is more stable at low temperatures and (ϕϕθ)/(ϕϕ2)nNH3]2CuCl4 also shows an interesting dependence on the length of the organic cation. At room temperature (ϕϕθ)//(ϕϕ6.n = 1 RP phases with (00θ)//2PbCl4 , are shown at temperatures above and below this phase transition in Fig. 7et al., 2015Cmce symmetry. The absence of ϕ-tilts and the presence of large θ-tilts can be clearly observed, along with the disorder of the BzA cations. Ignoring the disorder, the shortest H—Cl distance is 2.59 Å and the shortest distance between a hydrogen and a terminal chloride is 2.68 Å. In the low-temperature Cmc21 structure, the BzA cations adopt an ordered pattern and the terminal chloride ions shift toward two of the four neighboring –NH3+ groups. This leads to a pattern of strong hydrogen bonds with H—Cl distances of 2.33 to 2.35 Å and N—H—Cl angles ranging from 163 to 172° shown in Fig. 7e). These hydrogen bonds are comparable in strength to the strongest bonds observed in the low-temperature structure of (CH3NH3)2CdCl4 discussed above. The third hydrogen atom on the ammonium head group is equidistant between the two bridging chloride ions, forming a weaker bifurcated hydrogen bond with an H—Cl distance of 2.63 Å to both bridging chlorides.The relative abundance of hybrid 2+ ion shift in the same direction, which destroys the inversion center present in the high-temperature structure and bends the Cl—Pb—Cl bond angle from the linear 180° observed in the high-temperature structure to 168° [Figs. 7c) and 7f)]. As shown in Fig. 7e), half of the positively charged –NH3+ groups point in the direction parallel to [011] and the other half in the direction parallel to [011]. When combined the net result is a permanent dipole moment along the c axis, which is the polar axis for the Cmc21 space group. (BzA)2PbCl4 not only adopts a polar structure below 436 K, the polar axis can be reversed with an electric field making it a ferroelectric. It is notable that nearly all hybrid n = 1 RP phases showing this phase transition contain either Pb2+ or Sn2+. The 5s2/6s2 electron configuration of these ions may play a role in stabilizing the deformations of the octahedra that accompany the orientational ordering of the organic cations. A subtle distortion is also observed in the pattern of bonds in the plane defined by lead and the bridging chloride ions, with two Pb—Cl bond distances of 2.84 Å and two distances of 2.89 Å in the low-temperature Cmc21 structure. However, this type of distortion is also observed in Cd-containing RP phases with benzylammonium and cyclohexylammonium cations, so the attributes of the organic cation also plays a role.Interestingly, the terminal chloride ions above and below each Pb2+ or Sn2+ and (00θ)/2CH2CH2NH3+] and (IPA)2CdCl4  have room-temperature structures with (ϕϕ0)/(ϕϕ0) tilting and Cmce symmetry. In both compounds, a transition to the polar space group C2ce (or non-standard setting Aea2) driven by the orientational ordering of the organic cations occurs on cooling.Symmetry lowering due to orientational ordering of the organic cations is not exclusive to compounds containing PbA)2PbCl4 structure discussed above undergoes a Cmce to Cmc21 phase transition at ∼436 K 2PbBr4 also possesses Cmc21 symmetry 2PbI4 adopts a structure with (ϕϕθ)// of the I4/mmm parent structure and out-of-phase tilts about the a and b axes of the parent structure (ϕ-tilts). An additional 22 patterns of tilting are obtained when in-phase tilts (ψ-tilts) about the a and b axes are considered. The predicted structures have been compared with the structures of hybrid halide perovskites found in the CSD and ICSD. Of the 140 unique structures found in these databases, 123 (88%) adopt structures that are consistent with the predictions of the symmetry analysis. Of the 47 possible tilt systems, only 9 are observed experimentally (excluding the undistorted parent structure), none of which involve ψ tilts. In contrast, distortions involving both ϕ- and θ-tilts are common, accounting for ∼66% of the entries. The combination of ϕ- and θ-tilts is stabilized by favorable hydrogen bonding interactions between the organic cations and the inorganic layers. For the remaining 12% of the structures, the symmetry is further lowered by effects such as orientational ordering of the organic cations and/or distortions of the octahedra. Distortions that go beyond octahedral tilting are particularly prominent in compounds with (00θ)/(002+ or Sn2+ ions. In those compounds, distortions of the octahedra offer an alternate route to the formation of strong hydrogen bonding interactions.Using 10.1107/S2052252523003743/lt5057sup1.pdfSupporting figures and tables. DOI:


However, no one has ever observed the distribution of ligand holes in real space. Here, a successful observation of the spatial distribution of valence electrons in cubic perovskite SrFeO3 by high‐energy X‐ray diffraction experiments and precise electron density analysis using a core differential Fourier synthesis method is reported. A real‐space picture of ligand holes formed by the orbital hybridization of Fe 3d and O 2p is revealed. The anomalous valence state in Fe is attributed to the considerable contribution of the ligand hole, which is related to the metallic nature and the absence of Jahn‐Teller distortions in this system.An anomalously high valence state sometimes shows up in transition‐metal oxide compounds. In such systems, holes tend to occupy mainly the ligand  d orbital state in SrFeO3 but also provides insights into the distribution of ligand holes formed by Fe‐3d and O‐2p orbital hybridizations in real space. The absence of Jahn‐Teller distortions in the cubic structure and the metallic nature of this system are strongly associated with the presence of ligand holes.Electron density analysis using single‐crystal X‐ray diffraction not only reveals the Fe‐3 The ligand holes are considered to play a significant role in the electrical transport and magnetism in cuprates, nickelates, cobaltates, and ferrates.The ionic‐covalent character of the metal‐oxygen bonding in metal oxides has long been discussed. Since the oxygen and metal atomic orbitals mainly contribute to the bonding and antibonding orbitals, respectively, the bonding has a strong ionic nature and hence the formal ionic valence of metal can be well defined in general. Nonetheless, when the formal valence of metal is anomalously high, the contribution of the oxygen 2le state.1 The 3 is an archetypal tetravalent ferrate compound, in which at formally, four electrons occupy the Fe 3d orbitals. It forms the perovskite‐type structure with the cubic space group Pm3¯m  and the higher‐lying doublet (ge). The high‐spin state of 3d4 corresponds to the t2g3eg1 electron configuration, which causes some anisotropy in the valence electron density. However, previous X‐ray photoelectron spectroscopy and X‐ray absorption spectroscopy measurements suggest that the ground state consists of mixed 3d4 and 3d5L (L: ligand hole) states. In the extreme limit of the 3d5L state, the electron density around the Fe site should be spherical because of the t2g3eg2 electron configuration. Theoretically, the ligand hole formed by the 2p‐3d hybridization is expected to stabilize novel itinerant magnetic phases. In fact, despite its simple crystal structure, various magnetic phases including a quadruple‐q topological spin structure appear in the magnetic‐field‐versus‐temperature phase diagram in SrFeO3. Furthermore, the crystal structure and physical properties are greatly changed by slight oxygen vacancies, because this system has charge instability of unusual tetravalent iron cations.SrFeOm Figure 1a and ex  resolution is indispensable. In this study, we observe the valence electron density distribution of SrFeO3 by electron density analysis using state‐of‐the‐art synchrotron X‐ray diffraction (XRD). The number of 3d electrons is estimated from the anisotropic distribution of the valence electron density around the Fe site. It is also confirmed that the valence electron density around the O site along the Fe―O―Fe axis is slightly reduced.Although the ligand holes in the crystal have been observed by spectroscopy measurements,12 no 22.13 detected no structural phase transitions down to 30 K, which is consistent with the previous neutron diffraction experiment. As a result of the structural analysis, no signs of oxygen vacancy and no anomaly in the atomic displacement parameters of oxygen were confirmed. Here, the structural parameters were determined with high accuracy by performing a high‐angle analysis utilizing the advantages of high‐energy X‐rays, where only reflections with sin θ/λ > 0.6Å‐1 (d < 0.833Å) were used. The obtained structural parameters of SrFeO3 are summarized in Tables The XRD experiments of SrFeOperiment.23 As 2.23 at 30 K. No valence electron density larger than 3e/Å3 is observed around the Sr site, which is consistent with the Sr2 + (5s0) state. In contrast, valence electrons are observed around the Fe and O sites, as shown by yellow iso‐density surfaces. An orange iso‐density surface for higher electron distribution is observed only around the Fe site.Figure Figure m3¯m. The shape is clearly distinct from a sphere: there are six hollow holes toward the six ligand oxygens. To quantify the anisotropy of the valence electron density ρ(r) around the Fe site, the density at a distance r = 0.2Å from the Fe nucleus, which corresponds to the peak top of ρ(r)  for an isolated ion is related just to the spherical harmonics. A clear anisotropy shows up in the 3d4 state in contrast to the completely isotropic electron density in the 3d5 state. Here, we extract an approximate relation between the number of Fe 3d electrons eN and ρmin/ρmax; Ne=1.773(ρminρmax)2+1.163ρminρmax+2.096 (3 ≤ eN ≤ 5) by considering the experimental resolution (d > 0.28 Å) , which is consistent with the previous reports of X‐ray absorption spectroscopy measurement (eN =  4.7) and cluster model calculation (eN =  4.8).d orbital r = 0.2 Å. The electron density of Fe 3d calculated by the Slater‐type orbital (STO) of an isolated ion is also plotted as a red broken line, which is in good agreement with the experimental results in the [111] direction. Here, the experimental resolution d > 0.28 Å is considered when performing the inverse Fourier transform (the details are described in Supporting Information). On the other hand, the electron density in the [100] direction toward the ligand O has one clear peak corresponding to the 3d orbital with two shoulder‐like structures around r = 0.5 and 0.8 Å. The peak top of the electron density from the Fe nucleus is 0.05 Å closer in the [100] than in the [111] direction. These features may arise from the hybridization between the Fe 3d and O 2p orbitals.Radial distributions of the electron density along the [100] and [111] axes around the Fe site are shown in Figure lated ion29 is 2.3mm.m. Since the corresponding valence of Fe obtained by the CDFS analysis was 3.36(8) because of eN =  4.64(8), the oxygen valence is estimated to be − 1.79(3), which deviates from the ideal closed‐shell value of − 2. That is, the valence electron density distribution around the O site should not be isotropic. Figure r  =  0.40 Å from the O nucleus, obtained from the CDFS analysis. The observed electron density has some anisotropy. The highest electron density exists toward the surrounding four Sr atoms. On the other hand, the lowest electron density is observed in the [100] direction toward Fe. Brown and green dots in Figure r  =  0.4 Å, as shown in the pink line. We also confirmed that there is no significant anisotropy in the radial direction perpendicular to the [100] direction  well agrees with to the electron density of oxygen 2s22p6 (red broken line), whereas that in the [100] direction (brown dots) is lower. Furthermore, the difference between the electron densities in the two directions (pink line) mainly corresponds to the contribution of the electron density of oxygen 2p6 (orange broken line). These results suggest the existence of ligand holes accommodated in the O 2σp―Fe 3d antibonding (σ*) orbital, which is consistent with previous p‐d charge‐transfer cluster‐model calculations and small holes in O 2p densities of states predicted by first‐principles calculations. Furthermore, while a slight anisotropy in the charge distribution around the Fe site was predicted by the first‐principles calculations, the distribution of ligand holes around the O site was captured for the first time by the CDFS analysis.Finally, we focus on the valence electron density around the O site with the site symmetry 4/4+ and O2− states caused by the orbital hybridization as valence electron density distributions. The considerable contribution of the 3d5L state seems to be related to the metallic nature and absence of the Jahn‐Teller distortion. This unusual state, in which various magnetic phases appear in a magnetic‐field, is easily destroyed by slight charge shifts due to oxygen vacancies, resulting in changes in the crystal structure and the physical property. Thus, the observed p‐d hybridization may support the unstable charge state of this system. Our experimental technique will be useful in investigating changes in oxidation state due to oxygen vacancies in this system and negative charge transfer states in other systems such as YBa2Cu3O7−δ and SrCoO3 using the electron density analysis in the future.We observed deviations from ideal Fe33 has been investigated by synchrotron XRD experiments using a high‐quality single crystal. We have obtained the valence electron density distribution in SrFeO3 by the CDFS analysis. The number of Fe 3d electrons estimated by the anisotropy is eN =  4.64(8), which indicates the mixed 3d4 and 3d5L states. The ligand hole is directly observed around the O site. Our experimental observation of the ligand hole may be a touchstone for future theoretical calculations and offers new possibilities for the study of chemical bonding in transition‐metal compounds.The orbital state in SrFeO43 were obtained by high‐pressure oxygen annealing of large single crystals of the oxygen‐deficient perovskite SrFeO2.5 with brownmillerite‐type structure as described in Refs. , [Ar], and [He] type electron configurations were regarded as core electrons for Sr, Fe, and O atoms, respectively. As a result, Sr 5s, Fe 3d, and O 2s/2p valence electrons should remain after the subtraction of the core electron density distribution. The detailed process for extracting the valence electron density distribution was described in Ref. [A core differential Fourier synthesis (CDFS) method was used to extract the valence electron density distribution around each atomic site.36 [KrThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.


Mutant fish exhibited the behavioral phenotype observed in old animals and premature accumulation of neural cells positive for markers of cellular senescence, including senescence‐associated β‐galactosidase, elevated levels cdkn2a/b, cdkn1a, senescence‐associated secretory phenotype gene expression, and an increased level of DNA damage signaling. The behavioral and cell senescence phenotypes were reversed in mutant fish through treatment with the senolytic ABT263 or diverse PP2A activators as well as through cdkn1a or tp53 gene ablation. Senomorphic function of PP2A activators was demonstrated in mouse primary neural cells with downregulated Ppp2r2c. We conclude that PP2A reduction leads to neural cell senescence thereby contributing to age‐related behavioral changes and that PP2A activators have senotherapeutic properties against deleterious behavioral effects of brain aging.The contribution of cellular senescence to the behavioral changes observed in the elderly remains elusive. Here, we observed that aging is associated with a decline in protein phosphatase 2A (PP2A) activity in the brains of zebrafish and mice. Moreover, drugs activating PP2A reversed age‐related behavioral changes. We developed a transgenic zebrafish model to decrease PP2A activity in the brain through knockout of the  During aging, the activity of the Protein Phosphatase 2A (PP2A) declines in the brain of mice and zebrafish, leading to neural cell senescence and aged‐related behavioral changes. This process can be reversed by pharmacological activators of PP2A and senolytics. DDRDNA damage responseMPHmethylphenidateOToptic tectumPP2Aprotein phosphatase 2AROSreactive oxygen speciesRT‐qPCRreverse transcription‐quantitative polymerase chain reactionSASPsenescence‐associated secretory phenotypeWTwild‐type1A wealth of recent research indicates that cellular senescence is a basic aging process that greatly contributes to health deterioration and thereby critically impedes healthy aging , which reverses the phosphorylation of key actors in the DDR, such as γH2AX  exhibited a behavioral phenotype involving increased locomotor activity upon the transition between light and dark Figure , reflectMice at 14 months of age exhibited greater anxiety Figure , as well2.3ppp2r2c gene encoding a brain‐specific isoform of the regulatory subunits of PP2A  through the introduction of two different frameshift mutations within exon 9. These mutations led to a reduction of the mutant mRNA level, likely driven by nonsense‐mediated mRNA decay due to the presence of a premature stop codon  to y Figure  and revey Figure . That thppp2r2c in zebrafish led to the phenotype of aged WT zebrafish, which could be reversed by PP2A activators.In summary, two different loss‐of‐function mutations in 2.4ppp2r2c mutation leads to the observed behavioral deficit phenotype, we analyzed the quantities of 23 classical neurotransmitters in the brain of 6‐month‐old ppp2r2cm1/m1 and WT fish using liquid chromatograph mass spectrometer. Among the detected peaks, the only significant change was an increase in the level of L‐tyrosine in mutant fish and no alterations in the levels of catecholamines, including dopamine, were observed  analysis. Comparison of the ppp2r2cm1/m1 and WT brain transcriptomes revealed differential expression of 473 genes , Top2A and ligase 1  brain cells showed increased DNA damage signaling, as revealed by a higher proportion of nuclei harboring at least five γH2AX foci specifically in the optic tectum  specifically in the OT , DNA damage signaling , and senescence . This was seen both in tectal cells stained for NeuN (NeuN (+)), which marks developing, immature and mature neurons, and in cells that are NeuN (−). These results indicate that multiple types of neural tectal cells are altered upon ppp2r2c inhibition.In summary, 2.6ppp2r2c loss. To this end, we used RNAseq to identify genes with dysregulated expression in ppp2r2cm1/m1 compared to WT fish rescued by MPH treatment. We found 101 differentially expressed genes in the comparisons of ppp2r2cm1/m1 with WT and ppp2r2cm1/m1 without and with treatment  cells Figure . Moreovee Figure . These d2.7ppp2r2cm1/m1 fish. Therefore, we tested whether preventing or reversing senescence is sufficient to restore the behavioral deficits of mutant fish.The results presented above, namely that PP2A activators alleviate the behavioral abnormalities while also reversing senescence markers suggest that tectal cell senescence is involved in the behavioral deficit phenotype of tp53 and cdkn1a) that trigger senescence or treatment with the senolytic drug ABT263, which triggers apoptosis of senescent cells  cells of aged fish after MPH treatment , and neurons isolated from embryonic mouse brains , as well as by the reversal of the age‐related behavioral changes with PP2A activator treatment. Whether the behavioral effects of ppp2r2c loss described here are mechanistically related to the various human mental illnesses associated with ppp2r2c gene polymorphism and mouse (14 months). The association between the reduction of PP2A activity and age‐related changes was demonstrated by the similar behavioral phenotype observed in young fish with a mutated brain‐specific isoform of the PP2A regulatory subunit ) and non‐neuronal (NeuN (−)) cells exhibit senescence markers  as compared to WT adult and young zebrafish, respectively. This senescence phenotype is absent in fish treated with various PP2A activators, indicating that decreased PP2A in neural cells, whether due to the loss of ppp2r2c or natural aging, can lead to cell senescence. We also provide evidence that this senescence phenotype plays a role in the behavioral abnormalities observed in zebrafish. Indeed, they disappear with inactivation of the tp53 and cdkn1a genes or treatment with ABT263, which is a classical senolytic agent that provokes the apoptosis of senescent cells. Notably, in both types of zebrafish, the senescence phenotype triggered by PP2A activity impairment specifically affects the OT region of the brain. This localization likely stems from the higher level of ppp2r2c mRNA expression in neural cells of the OT relative to other parts of the brain  can be a substrate of PP2A  activates PP2A activity in aged brains, attenuates the DDR, and reduces the abundance of SA‐β‐gal‐positive neurons. This mechanism can explain the findings of recent clinical studies showing that treatment with MPH improves the outcomes of age‐related dementia (Padala et al., Our results link PP2A, brain aging, neural senescence, and age‐related behavioral changes. We propose that the age‐related decrease in PP2A activity increases the level of DDR leading to neural senescence, neuroinflammation, and behavioral changes. An important finding of this study is that drugs with PP2A activation activity can prevent age‐related cognitive decline. In particular, we revealed that the classical psychostimulant MPH (Ritalin 4Experimental details can be found in the Methods and Materials JY and EG designed the experiments. JX, KHC, SYG, YLY, BW, CCW, and LXC performed the experiments. JY, YML, and EG analyzed the data. EG and JY wrote the paper.The authors have declared that no conflict of interest exists.Appendix S1Click here for additional data file.Table S1Click here for additional data file.Table S2Click here for additional data file.Table S3Click here for additional data file.Table S4Click here for additional data file.Figures S1‐S10Click here for additional data file.Appendix S2Click here for additional data file.


Dear Editor,Neuroradiology. The authors conclude that the trials’ data do not support thrombectomy in patients with an ischemic core exceeding 150 ml and recommend a case-by-case decision for patients with larger cores than 150 ml. They do, however, not discuss the reliability and accuracy of ischemic core assessment in these 3 RCTs [This letter to the editor comments on the results of 3 recent randomized controlled trials (RCTs) on the efficacy and safety of thrombectomy in stroke patients with large ischemic cores . This toe 3 RCTs –4 and doThe Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism–Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT) has used non-contrast CT in 28 of 203 study participants (14%) and DWI in 175 study participants (86%) to determine the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of early ischemic changes being considered “infarctions” without prove [−6 mm2 per second as “core infarct.” The full-analysis population included 60 study participants with an ASPECTS < 3 (24%). Follow-up imaging was performed at 36 h with MRI or at 7 days with non-contrast CT. The “change from baseline in infarct-core volume” is presented in table 2 without dimension and thus hard to interpret. It remains unknown in how many patients a shrinkage of the initial “infarct-core volume” was observed.The ANGEL-ASPECT investigators included all patients with an ASPECTS of 3 to 5 on non-contrast CT and, in addition, patients with an ASPECTS < 3 and > 5 if the “infarct-core volume” was between 70 and 100 ml [−6 mm2 per second [The SELECT2 investigators like the ANGEL-ASPECT investigators included all patients with an ASPECTS of 3 to 5 on non-contrast CT and in addition patients with an estimated ischemic-core volume of ≥ 50 ml on CTP maps  or a lesion with a volume of ≥ 50 ml with an ADC of less than 620 × 10r second . Based o−6 mm2 per second for the delineation of ischemic cores is based on a study in 14 patients only that showed a sensitivity of 69% and a specificity of 78% for the identification of ischemic core brain tissue [Despite these different approaches for including stroke patients with an ASPECTS of 3 to 5 and the additional inclusion of patients with an ASPECTS < 3 and a volume of ischemic core ≥ 150 ml, thrombectomy being performed within 24 h after stroke onset was beneficial and not associated with symptomatic intracranial hemorrhages in all 3 RCTs irrespectively whether a mismatch profile was present [In the past, very many ischemic stroke patients remained untreated because of unwarranted restrictions. Intravenous thrombolytics (IVT) were not recommended if patients presented after 3 h, although no RCT had shown that late treatment is associated with an increased risk. ECASS 3 then showed the small benefit of IVT if applied between 3 and 4.5 h after stroke onset . The metAn ASPECTS of 0 means that all middle cerebral artery subterritories are affected by ischemic changes but tell nothing about the territory supplied by the anterior and posterior cerebral artery that may be at risk if the internal carotid artery (ICA) is occluded which was the case in 36 to 47% in the 3 RCTs discussed here. The ASPECTS of ischemic brain tissue changes should be considered only in relation to the arterial occlusion site, the collateral blood flow, and the National Institute of Health Stroke score. Any cut-off threshold may mean that ischemic stroke patients with a chance to improve with thrombectomy will not be treated.


The anode−side interfacial IMC is dominated by a Cu6Sn5 phase with a gradually increasing thickness, forming a Cu3Sn phase and showing evidence of microcracks. The Cu6Sn5 phase of the cathode−side interfacial IMC is gradually completely dissolved, and the growth of the Cu3Sn phase is accompanied by the formation of Kirkendall voids. The anisotropic diffusion of Cu atoms in the β−Sn of the micro−solder joints causes increased solder joint resistance and reduced shear strength. The shear fracture path of the solder joints moves from the cathode side near the IMC solder seam to the Cu3Sn interface. The shear fracture mechanism changes from ductile transgranular fracture dominated by β−Sn dimples to brittle fracture dominated by interfacial IMC cleavage and slip steps.To solve the electromigration problem of micro−electronic connection solder joints, an ideal electromigration tester was designed, and the thickness of the intermetallic compounds (IMCs), average void diameter, grain orientation, failure, shear strength, and fracture path of Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints under constant−temperature electromigration were studied. The results indicate that the solder joints show evidence of typical electromigration polarity in the asymmetric growth of interfacial IMCs on the anode and cathode sides under the conditions of a current density ≥7 × 10 In f the IC ,6,7,8, rf the IC ,11,12,13Thermostatic electromigration refers to the mass transfer behavior of lead−free solder joints at a constant temperature driven by the “electron wind” generated by a high current density and controlled by diffusion ,16,17,184 A/cm2 and above [4 A/cm2. Yao et al. [4 A/cm2. It was also observed that the IMC on the anode side of the solder joint gradually thickened with the loading time, while the IMC on the cathode side grew very slowly and produced an electromigration polarity with microcracks. In their research on the relevant factors affecting electromigration polarity in Sn3.0Ag0.5Cu/Cu lead−free solder joints, Wang et al. [6Sn5 grains on both sides of the interface fused. As Sn gradually depleted, the Cu matrix continued to react with Cu6Sn5 to form a layered Cu3Sn [Firstly, scholars explored different samples and test devices in electromigration research. Bashir et al.  designednd above , suggesto et al.  conducteg et al.  found thg et al.  conducteed Cu3Sn . As thised Cu3Sn  Sn−Ag−Cued Cu3Sn  found thed Cu3Sn  studied ed Cu3Sn . HoweverIn summary, based on the latest progress in electromigration research, we designed and constructed an electromigration test device for Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints in an ideal environment and observed and analyzed the correlation mechanism between IMC growth and β−Sn grain orientation. Here, we propose an electromigration theoretical model based on atomic diffusion theory, having tested and analyzed the service life and mechanical fracture path of the solder joints, thus laying a foundation for the design and manufacturing of highly reliable micro−solder joints under real dynamic temperature gradient conditions. The results of this research are, thus, of great significance to the electronic information manufacturing industry.The low−silver Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs solder used in this paper is lower in cost than the mainstream SAC305 solder and has good wettability. According to the study of Wang et al. , the addIn this study, the thermal decomposition method was used to prepare the Ni−GNSs reinforcement phase required for the test. Sn, Ag, Cu, and mixed rare earth powder with a purity of more than 99.99%, together with the prepared Ni−GNSs enhancement phase, were mixed to form a Sn2.5Ag0.7Cu0.1RE0.05Ni−GNS composite solder. After being compacted, the mixed solder powder was sintered in a vacuum furnace at 180 °C for 2 h to obtain the Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs composite solder required for the test.2. When a current of 0–50 A is applied, a current density of 0–104 A/cm2 can be obtained.The shape and size of the sample used in this test in order to reduce the Joule heat and eliminate the impact of thermal migration on the electromigration are shown in Brazing: After polishing and cleaning the surface to be welded and the filler metal sheet, one applies 1–2 drops of commercial CX600 water to wash the solder, places it into the brazing furnace, and obtains the solder joint after cooling. According to the literature , the braThe operating principle of the designed and manufactured electromigration tester is shown in Ideal electromigration environment: To prevent the current crowding effect and thermogradient of solder joints from interfering with the electromigration under current loading conditions, this test device was current−loaded to detect the temperature difference between the anode and cathode of the solder joints in the air environment and oil bath (dimethyl silicone oil) environment so as to determine the ideal electromigration test environment. In this test, the height of the Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints was 0.2 mm, and a thermomigration critical condition of 1000 °C/cm  was used3 to 1 × 104 A/cm2, and the loading times were 50 h, 100 h, 150 h, 200 h, 250 h, 300 h, and 350 h, respectively. The solder joints were inlaid, ground, and polished at the end of the tests. The microstructure and morphology of the solder joints were observed using a scanning electron microscope (JSM−5610LV) , and the composition of the solder joints was tested using an energy−dispersive spectrometer  . The average thickness of the interfacial IMC and the average diameter of the voids were measured using the Photoshop image processing software. After the surface stress of the solder joints was eliminated using a precision sub−ion beam polisher (1061 SEM Mill) , the grain orientation was analyzed using electron back−scattering diffraction  of the SEM. The shear test was conducted on a UTM2503 micro−tensile testing machine  .An oil bath temperature of 150 °C was selected as the electromigration test temperature condition because the ideal electromigration of solder joints is likely to occur when the temperature (T > 100 °C) and β−Sn grains (T < 161 °C) are in a steady state . The tec6Sn5, and the generation of Cu3Sn is not observed. The interfacial IMC on both sides grows symmetrically, has a basically consistent thickness and morphology, and a respective average thickness of 4.1 μm/4.3 μm, with a continuous, smooth “scallop shape”. According to the X−ray diffraction (XRD) analysis of Region A in 6Sn5 and needlelike β−Sn + Ag3Sn binary eutectic structure and the β−Sn + Cu6Sn5 + Ag3Sn ternary eutectic structure. According to the EDS analysis of Region B in 3 A/cm2) grow symmetrically, and no obvious electromigration occurs. The interfacial IMC on both sides is mainly a continuously distributed scallop−shaped Cu6Sn5 layer and has an average thickness of 8.4 μm, and no Cu3Sn phase is observed. One can observe clear asymmetric growth on both sides of the interfacial IMC of the solder joints (j = 4 × 103 A/cm2 and 7 × 103 A/cm2), and the interfacial IMC on both sides consists of a thick Cu6Sn5 layer near the solder seam side and a Cu3Sn thin−strip layer near the Cu substrate side, showing evidence of clear electromigration polarity. With an increase in the current density to 1 × 104 A/cm2 from 7 × 103 A/cm2, the thickness of the interfacial Cu6Sn5 layer at the anode increases to 13.9 μm from 11.7 μm. The morphology grows from a continuous “strip shape” and blends to form a discontinuous “lamellar shape”. Microcracks appear in the Cu3Sn layer due to the impact of stress, and the microcrack size increases with an increase in the current density. The thickness of the interfacial Cu6Sn5 layer at the cathode decreases to 2.4 μm from 5.1 μm, and the number of Kirkendall voids in the Cu3Sn layer affected by diffusion increases, forming large cracks between the interfacial IMC and the solder seam.3 A/cm2) consists of multiple sub−grains with two main types of grain orientations and has a maximum grain diameter of 154.2 μm. Its <001> crystalline phase shows a clear preferential orientation. As can be seen in the corresponding unit cell diagram, the included angle between the c−axis and the current direction θ is large, at 71.5–83.6°. The β−Sn grains hinder the diffusion of Cu atoms. The Cu6Sn5 grain orientation is relatively disordered. The grain diameter is in a range of 2.7 μm–7.6 μm, the high−angle grain boundary is large, and the grain boundary energy is also large. Significant growth of the Cu6Sn5 grains is not likely to occur at this current density. As shown in 3 A/cm2, the β−Sn in the solder joints consists of multiple grains with three main types of grain orientations and has a maximum grain diameter of 143.7 μm. The included angle between the c−axis of the β−Sn and the current direction θ is small, at 33.6–53.2°. The diffusion of Cu atoms mainly derives from the dissolution of the Cu substrate and the migration of cathode−side Cu atoms. The interfacial IMC at the anode forms multiple Cu6Sn5 recrystallized grains. The interfacial grains on both sides have a diameter of 4.2 μm–20.8 μm. The newly formed Cu6Sn5 grains in the near−solder−seam region are small and have a relatively disordered orientation. As shown in 4 A/cm2, the β−Sn in the solder joints consists of multiple grains with two main types of grain orientations and has a large β−Sn grain diameter of 134.3 μm. The included angle between the c−axis and the current direction θ further decreases to 12.1°, causing increased diffusion of Cu atoms in the solder seam, so that the diameter of the interfacial Cu6Sn5 grains at the anode further increases. Therefore, when the welding point j ≥ 7 × 103 A/cm2 and θ ≤ 53.2°, there is significant electromigration polarity. As the current density increases, the θ angle between the c−axis of the β−Sn grains and the direction of the electron flow decreases. The reduction promotes the dissolution of the Cu substrate and the migration of the cathode Cu atoms to the anode. Cu3Sn is formed at the interface between the two electrodes, and the Cu6Sn5 grains undergo recrystallization and growth. The crack size gradually increases, as shown in the schematic diagram of the solder joints loaded for 200 h at different current densities in The orientation analysis of the crystal structure of the Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints at different current densities is shown in 3 A/cm2) process. 6Sn5 layer on both sides slightly thickens due to the impact of Joule heat; and a Cu3Sn layer is not formed during the 0 h–100 h loading period. As can be seen from the corresponding 6Sn5 grains mainly derives from the melting of the substrate. In this period, the growth of the anode−side interfacial IMC is in an “incubation stage”, and the cathode−side cracks are in the nucleation stage.6Sn5 layer at the anode linearly increases from 3.7 μm to 6.7 μm due to the impacts of the temperature and “electron wind force”, and the Cu3Sn layer starts to form with a thickness of 1.6 μm. The corresponding interfacial Cu6Sn5 layer at the cathode starts to dissolve, and the thickness decreases in a power−exponential manner. Small Kirkendall voids start to form, so that the Cu6Sn5 layer dissolution rate is equal to the Cu3Sn layer formation rate. However, the total thickness of the IMC at both ends, the thickness difference of the IMC between the two sides, and the total amount of atom migration increase. As can be seen from the corresponding 6Sn5/Sn interface at the anode along the β−Sn grain boundary. The Cu substrate at the anode also quickly dissolves. Cu3Sn starts to form at the Cu/Cu6Sn5 interface, and the interfacial IMC starts to form microcracks due to the impact of stress. The dissolution of the Cu substrate and Cu6Sn5 layer at the cathode causes Kirkendall voids to appear at the cathode−side interface. In this period, the growth of the anode−side IMC is in an “expansion stage”, which corresponds to the microcrack expansion stage of the cathode−side IMC.As can be clearly seen from 6Sn5 or Cu3Sn layers grow significantly, and interfacial IMC cracks expand rapidly. The Cu6Sn5 layer at the cathode side interface rapidly dissolves, the size of the Kirkendall voids increases, and cracks form near the brazing seam area of the IMC. The thickness of the Cu3Sn layer decreases slightly due to the influence of the crack size. As can be seen from the corresponding 3Sn/Cu6Sn5 layer mainly by bulk diffusion, which requires greater energy than grain boundary diffusion. The growth of Cu6Sn5 can only be supported by Cu element migration in the solder seam, causing a slow increase in the anode−side IMC thickness during this period. The total thickness of the IMC on both sides is even reduced. The total amount of atom migration decreases. This period is a “stability stage” for the growth of the anode−side interfacial IMC, which corresponds to the macrocrack expansion stage of the cathode−side interfacial IMC.As can be seen from 3Sn/Cu6Sn5. The increase in the Cu6Sn5 brittle phase on the anode side causes an increase in the number of cracks, further dissolution of the Cu substrate, and an acceleration in IMC growth until the entire solder seam is fully filled. In this period, the growth of the anode−side IMC reaches the “failure stage”, while the growth of the cathode−side IMC is in the fracture stage.As can be seen from chemJ and EMJ, respectively. The diffusion flux under the chemical formula driving force is obtained according to Fick’s first law Equation (1) [J is the diffusion flux, D is the diffusion coefficient, and dC/dx is the concentration gradient. The diffusion coefficient D is obtained from the Arrhenius equation. The diffusion flux caused by the electron wind force is expressed as Equation (2) [C is the concentration of diffusing atoms, K is the Boltzmann constant, T is the absolute temperature, Z* is the number of effective charges, e is the electron charge, ρ is the resistivity, and j is the current density. Equation (3) [The asymmetric growth in the interfacial IMC in the electromigration of the Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints depends on four factors: the dissolution rate of the substrate and IMC at the cathode, the migration rate of Cu and Sn atoms in the solder seam, the dissolution rate of the substrate at the anode, and the reaction rate of the anode−side interfacial atoms. All the reaction rates must take into consideration the diffusion and migration fluxes under the combined driving force of the chemical formula of Cu and Sn atoms (mainly the concentration gradient) and the electron wind force, which are tion (1) :(1)Jchemtion (2) :(2)JEM=Ction (3) , for theT and j, which indicates that the electromigration process is one of long−term accumulation under the combined effects of heat and electron wind. The atomic migration under current loading is shown in chemJ = GBJ + BJ (where BJ is the bulk diffusion flux and GBJ is the grain boundary diffusion flux). The anode−side interfacial atom reaction flux is J1 = GBJ1 + BJ1 + EMJ − solderJ1 (where solderJ is the flux of the IMC diffused into the solder seam). The cathode−side interfacial atom reaction flux is J2 = GBJ2 + BJ2 − EMJ − solderJ2.In Equation (3), J is correlated with 3 A/cm2). As can be seen from this figure, the EMJ direction always points to the anode. As shown in J1 is equal to J2, and the total amount of atom migration remains unchanged in this period. As shown in GBJ1 + BJ1 > GBJ2 + BJ2, solderJ1 < solderJ2, J1 > J2; the total amount of atom migration increases; and the direction points to the anode in this period. As shown in GBJ1 + BJ1 < GBJ2 + BJ2, solderJ1 > solderJ2, J1 < J2; the total amount of atom migration decreases; and the direction points to the cathode in this period. As shown in GBJ1 + BJ1 > GBJ2 + BJ2, solderJ1 > solderJ2, J1 > J2; the total amount of atom migration increases; and the direction points to the anode in this period.A is a constant, j is the current density, n is the current density exponent , k is the Boltzmann constant, T is the absolute temperature, and Q is the diffusion activation energy.In electromigration studies, the “mean time to failures” (MTTFs) is usually used to detect the service lift of solder joints. MTTF refers to the time required for the occurrence of electromigration failure in 50% of the interconnected leads. A solder joint fails when its resistance value rises by 100%. According to Black’s formula (4) ,(4)MTTF3 A/cm2) process was obtained, as shown in In this study, solder joints with a certain combination of electrical and mechanical properties were tested in the current loading process to better evaluate their service life . A fitte3 A/cm2). 6Sn5 phase. The fracture location moves from the solder seam to the end of the Cu6Sn5/Sn interface 3 A/cm2 and included angle between the c−axis of the β−Sn grains and the current direction θ ≤ 53.2°. The anode−side interfacial IMC of the solder joints is dominated by a Cu6Sn5 phase, has a gradually increasing thickness, forms a Cu3Sn phase, and shows evidence of microcracks. The Cu6Sn5 phase of the cathode−side interfacial IMC is gradually completely dissolved, and the growth of the Cu3Sn phase is accompanied by the formation of Kirkendall voids.With the ideal self−designed and manufactured electromigration device, Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints show evidence of typical electromigration polarity under the conditions of a typical electromigration polarity ≥ 7 × 10(2)The anisotropic diffusion of Cu atoms in β−Sn in the electromigration of Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder points affects four stages of electromigration: the incubation stage, expansion stage, stability stage, and failure stage. The process of electromigration can be decelerated through the reasonable adjustment and control of θ.(3)3Sn interface. The shear fracture mechanism changes from ductile transgranular fracture dominated by β−Sn dimples to brittle fracture dominated by interfacial IMC cleavage and slip steps.In the four stages of electromigration of Sn2.5Ag0.7Cu0.1RE0.05Ni−GNSs/Cu solder joints, the increase in the resistance is inversely correlated with the decrease in the shear strength, and the solder joints reach the failure state at 250 h. The shear fracture path of the solder joints moves from the cathode side near the IMC solder seam to the Cu


An artificial topology phenomenon is observed in the Fe5GeTe2/MnPS3 heterostructure by using both anomalous Hall Effect and reflective magnetic circular dichroism (RMCD) measurements. Through tuning the applied current and the RMCD laser wavelength, the amplitude of the humps and dips observed in the hysteresis loops can be modulated accordingly. Magnetic field‐dependent hysteresis loops demonstrate that the observed artificial topological phenomena are induced by the generation and annihilation of the magnetic domains. This work provides an optical method for investigating the topological‐like effects in magnetic structures and proposes an effective way to modulate the magnetic properties of magnetic materials, which is important for developing magnetic and spintronic devices in van der Waals magnetic materials.2D ferromagnet is a good platform to investigate topological effects and spintronic devices owing to its rich spin structures and excellent external‐field tunability. The appearance of the topological Hall Effect (THE) is often regarded as an important sign of the generation of chiral spin textures, like magnetic vortexes or skyrmions. Here, interface engineering and an in‐plane current are used to modulate the magnetic properties of the nearly room‐temperature 2D ferromagnet Fe 5GeTe2. An artificial topology phenomenon is observed in the Fe5GeTe2/MnPS3 heterostructure which is induced by the generation and annihilation of the magnetic domains.2D ferromagnet is a good platform to investigate topological effects and spintronic devices. Herein, interface engineering and an in‐plane current are used to modulate the magnetic properties of the nearly room‐temperature 2D ferromagnet Fe These have been reported in magnetic multilayers, topological insulators, and heavy metal/ferromagnet systems. Furthermore, with a variety of vdW magnetic materials, the magnetic domain structure can be efficiently tuned by a current or the nearest neighbor materials, thereby yielding some new physical phenomena.Since the discovery of 2D van der Waals (vdW) magnets, significant interest in 2D magnets has emerged, inspired by their appealing physical properties and integration ability with other 2D materials to form artificial heterostructures. 2D vdW heterostructures provide an alternative bond‐free integration strategy without lattice and processing constraints, forming sharp atomic interfaces with vdW interaction between different layers. These advantages minimize chemical modification and interfacial damage, which is desirable for engineering a clean interface for optimal interactions.6, 7 Reflective magnetic circular dichroism (RMCD) is an optic technique that is usually used to characterize the magnetism of 2D magnets. The non‐contact and non‐destructive measurement features and the wavelength‐ and spatial‐resolution abilities made it to be a powerful method for investigating the magnetism of 2D magnets without disturbing their intrinsic properties.Topological Hall Effect (THE) is a spin‐chirality‐driven hall effect and the humps or dips near the magnetic phase transition in the hall signal were considered as a feature of the nontrivial spin texture. However, without direct imagination of the chiral magnetic structures by using magnetic force Microscopy or Lorentzian transmission electron microscopy, it is hard to identify the magnetic skyrmions by hallmark alone. The coexistence of the two components’ anomalous Hall Effect may also give rise to the nonmonotonic hysteresis shape that is similar to genuine THE, making it difficult to recognize the genuine THE.20 Ref5GeTe2 is a potential candidate for the development of novel room‐temperature spintronic devices, whose Curie temperature (Tc) in the 2D limit is close to room temperature. However, due to the complex atomic structure, the magnetic behaviors of Fe5GeTe2 have not yet been clearly explored. Therefore, a systematic study of the magnetic properties of Fe5GeTe2 is needed. In this work, we systematically investigated the magnetic properties of Fe5GeTe2 and Fe5GeTe2/MnPS3 heterostructures. Interface engineering and in‐plane current application could tune the magnetic properties of Fe5GeTe2 in opposite ways. When a proper in‐plane current was applied to the Fe5GeTe2/MnPS3 heterostructures, an anomalous RMCD hysteresis loop with a hump‐like feature similar to that of THE hysteresis loops could be observed. However, the minor‐loop measurements confirm that this anomalous RMCD signal is not a topological phenomenon, but a magnetic phenomenon generated by the generation and annihilation of the inhomogeneous magnetic domains. These intriguing results provide new insights into novel physical phenomena in 2D ferromagnets and will play a significant impact on the future development of 2D spintronics.Recent works have demonstrated that Fe devices,22 who22.15GeTe2 belongs to the crystal family of FenGeTe2 , which has a structure similar to that of Fe3GeTe2.Figure5GeTe2 crystal, which is composed of Fe–Ge slabs sandwiched by two Te layers. In each unit cell, there are three Fe sites. The Fe(1) site is regarded as a split site and is located either above or below the Ge site, which makes the crystal structure complex and then produces nontrivial spin structures. Figure M–T) of the bulk Fe5GeTe2 single crystal acquired via a superconducting quantum interference device (SQUID) under an external magnetic field of H = 100 Oe. As the temperature decreases, the out‐of‐plane magnetization (H//c) exhibits a weak temperature dependence after a rapid increase near Tc. In contrast, the in‐plane magnetization (H//ab) under the same conditions exhibits significant enhancement in a certain temperature range. A small spike at ≈T = 263 K and a broad cusp at 100–250 K indicate competition among the ferromagnetic exchange interaction, dipolar interaction, magnetic anisotropy, and DMI. In addition, the isothermal M–H curves at different temperatures for both field directions are shown in Figure ab plane) direction to the out‐of‐plane direction (c‐axis). During the whole cooling process, the competition between in‐plane magnetization and out‐of‐plane magnetization is extremely likely to induce spin rearrangement and generate diverse magnetic domain structures. While for thin Fe5GeTe2 flake, the magnetic domain structures seem independent with thermal cycling treating processes, since the RMCD hysteresis curves taken at the same temperatures are almost the same after any thermal cycling treating processes  measured by transport and RMCD are very close. Anomalous hump‐like features could be observed clearly in both hysteresis curves, which means that the RMCD results could reproduce the transport results perfectly in Fe5GeTe2 and its heterostructures systems. Therefore, we will use RMCD methods instead of the transport method to investigate the magnetic properties of Fe5GeTe2 and Fe5GeTe2/MnPS3 in the following context.Fe2.25GeTe2/MnPS3 heterostructure, we first performed current‐ and wavelength‐dependent RMCD measurements for a Fe5GeTe2/MnPS3 heterostructure. As shown in Figure5GeTe2/MnPS3 heterostructure with an in‐plane current of 5 mA applied to it, hysteresis loops with hump and dip could be observed (Sample 2), which is quite distinct from the ordinary RMCD signal in Fe5GeTe2  and its Fe5GeTe2/MnPS3 heterostructure (Sample HS‐A), respectively. The incident light is 700 nm with a beam spot of 10 µm and a detection power of 5–10 µW. As indicated in the figure, at temperatures lower than 180 K, a contracted coil‐shaped hysteresis loop is present in Fe5GeTe2. In contrast, the RMCD loop in the Fe5GeTe2/MnPS3 heterostructure is irregular below 260 K, where the RMCD value above the saturation field is much smaller than the maximum value. A more detailed study will be given in the following section. Figure 5GeTe2 and Fe5GeTe2/MnPS3 as a function of temperature at μ0H = 0. The residual magnetism of the Fe5GeTe2/MnPS3 heterostructure is several times larger than that of the Fe5GeTe2 counterpart, which means that the proximity coupling effect of Fe5GeTe2/MnPS3 could significantly enhance the magnetic properties of Fe5GeTe2. Then, a thinner Fe5GeTe2 flake (Sample B ≈ 20 nm) and its Fe5GeTe2/MnPS3 heterostructure (Sample HS‐B) were fabricated and comparatively investigated. The results are consistent with the previous results, where the coercive field (Hc) of Fe5GeTe2 is significantly enhanced by the interface of Fe5GeTe2/MnPS3 heterostructures  gradually decrease as the current increases. This indicates that the in‐plane current could drive the motion of the domain walls and disturb the magnetic order of Fe5GeTe2, effectively weaken its magnetic anisotropy.To evaluate the effect of MnPS5GeTe2 in opposite directions, the influences of the interface effect and the current on magnetic domains are not negligible. Thus, it is very possible to generate chiral spin structures and a hump‐like feature. However, it may not be appropriate to equate it with the topological Hall signal simply by virtue of this hump feature, which may also be generated by the superposition of multiple magnetic signals. Therefore, we need more experimental data to confirm our speculations on this controversial issue in the field.The above studies illustrate that interface engineering and in‐plane current application are two effective ways to modulate the magnetic anisotropy of Fe2.4 For the genuine THE, the appearance of dips and humps in the minor loops does not depend on the history of the sweeping magnetic field, while the opposite occurs for the artificial ones. Figure5GeTe2/MnPS3 heterostructure (Sample 3) at 120 K with 0.5 mA current applied to it. The minor loops were taken by sweeping the magnetic field from +800 mT to zero or a certain value of negative field  and then back to +800 mT. As presented in Figure 5GeTe2 body part, which have the opposite RMCD signals. In addition, for the irregular hysteresis loop shown in Figure To distinguish whether the hump‐like feature is a genuine topological phenomenon, the measurement of minor loops was performed.32 For5GeTe2 is ≈20 nm). Figure5GeTe2/MnPS3 heterostructure (Sample HS‐B) taken at various wavelengths under 10 K. For the hysteresis curve taken at 560 nm, the loop shape is regular, whereas for the data taken at 640–820 nm, the loop shapes are irregular. As the wavelength changes, the shape varies accordingly. To rule out the possible effect of electron transfer between MnPS3 and Fe5GeTe2, the absorption spectrum of MnPS3 (550–600 nm) and excitation power‐dependent RMCD of the heterostructures were characterized , Fe5GeTe2 (Sample B ≈ 20 nm) and Fe5GeTe2 (Sample A ≈ 30 nm) are given in the Figures 5GeTe2 play an important role in generating such irregular hysteresis loops. And as shown in Figure 5GeTe2. Due to Kramers–Kronig relations, the RMCD intensity in these two regions is wavelength dependent and responds differently, thus leading to a change in the hysteresis shape. Then, when in‐plane current acts on the Fe5GeTe2/MnPS3 heterostructures, the influence of the current on the magnetic domains in the two regions is not uniform, so the RMCD signal in Figure To clarify the origin of the irregular RMCD signal, wavelength‐dependent RMCD measurements were taken at wavelengths ranging from 500–900 nm at 10 K for Sample HS‐B , P (99.999%), and S (99.999%) in a 1:1:3 ratio were used and ground uniformly in an N2‐protection glove box. The mixture was then sealed into a quartz ampule with appropriate iodine. Finally, the ampule was placed into a horizontal two‐zone furnace with a hot zone at 953 K and a cold zone at 873 K for eight days and cooled with 3 K min−1 to room temperature. The Fe5GeTe2 Single‐crystal was purchased from Shanghai Onway Technology Co., Ltd. The crystal structure of both crystals was checked by X‐ray diffraction (XRD).The MnPS5GeTe2 and MnPS3 thin flakes, dry transfer method was used to fabricate Fe5GeTe2/MnPS3 heterostructures. To prepare the Fe5GeTe2/MnPS3 heterostructure, Fe5GeTe2 and MnPS3 crystals on polydimethylsiloxane and selected flakes with suitable thickness were first mechanically exfoliated under a microscope. Then, the multilayer Fe5GeTe2 flakes were transferred onto Si/SiO2 substrates, and an MnPS3 flake was stacked on Fe5GeTe2 by the dry transfer method. The whole process was performed in a glovebox, and the sample was sealed in a copper box during measurement, thus avoiding oxidation due to exposure to air.Mechanical exfoliation methods were used to prepare Fe5GeTe2 and MnPS3 single crystals  was performed to check the interfacial structures of Fe5GeTe2/MnPS3 heterostructures  was used to fabricate Cr/Au (10/90 nm) electrodes through electron beam evaporation. After the lift‐off process, electrodes were obtained. In the preparation of completely oxidation‐free samples, Cr/Au electrodes were first prepared on a Si/SiORMCD and MOKE measurements were performed in a superconductive magnet (Oxford Instruments) with a temperature range of 300–4.2 K and an out‐of‐plane magnetic field up to 5 T. The light source had a wavelength range from 500–900 nm. The signal was collected by a pre‐amplified photodetector connected to three lock‐in amplifiers (LIAs).28The electrical measurement module was integrated with the RMCD measurement setup, and RMCD, MOKE, and magneto‐transport measurements could be conducted simultaneously under the same experimental conditions. Detailed information about the setup is given in Figure The authors declare no conflict of interest.Supporting InformationClick here for additional data file.