Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis.

An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency promotes adipogenic differentiation of MSCs by blocking autophagic flux in osteoporosis. However, the function of APPL1 in the osteogenic differentiation of MSCs remains unclear. This study aimed to investigate the role of APPL1 in the osteogenic differentiation of MSCs in osteoporosis and the underlying regulatory mechanism. In this study, we demonstrated the downregulation of APPL1 expression in patients with osteoporosis and osteoporosis mice. The severity of clinical osteoporosis was negatively correlated with the expression of APPL1 in bone marrow MSCs. We found that APPL1 positively regulates the osteogenic differentiation of MSCs in vitro and in vivo. Moreover, RNA sequencing showed that the expression of MGP, an osteocalcin/matrix Gla family member, was significantly upregulated after APPL1 knockdown. Mechanistically, our study showed that reduced APPL1 impaired the osteogenic differentiation of mesenchymal stem cells by facilitating Matrix Gla protein expression to disrupt the BMP2 pathway in osteoporosis. We also evaluated the significance of APPL1 in promoting osteogenesis in a mouse model of osteoporosis. These results suggest that APPL1 may be an important target for the diagnosis and treatment of osteoporosis.

Development of a novel 3D perfusable vascular graft model to elucidate the mechanisms for congenital heart disorders.

Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.

A Combined UWB/IMU Localization Method with Improved CKF.

Aiming at the problem that ultra-wide band (UWB) cannot be accurately localized in environments with large noise variations and unknown statistical properties, a combinatorial localization method based on improved cubature (CKF) is proposed. First, in order to overcome the problem of inaccurate local approximation or even the inability to converge due to the initial value not being set near the optimal solution in the process of solving the UWB position by the least-squares method, the Levenberg-Marquardt algorithm (L-M) is adopted to optimally solve the UWB position. Secondly, because UWB and IMU information are centrally fused, an adaptive factor is introduced to update the measurement noise covariance matrix in real time to update the observation noise, and the fading factor is added to suppress the filtering divergence to achieve an improvement for the traditional CKF algorithm. Finally, the performance of the proposed combined localization method is verified by field experiments in line-of-sight (LOS) and non-line-of-sight (NLOS) scenarios, respectively. The results show that the proposed method can maintain high localization accuracy in both LOS and NLOS scenarios. Compared with the Extended Kalman filter (EKF), unbiased Kalman filter (UKF), and CKF algorithms, the localization accuracies of the proposed method in NLOS scenarios are improved by 25.2%, 18.3%, and 11.3%, respectively.

Generation of a modulated versatile spiral beam with varying intensity distribution along the propagation.

A new type of versatile spiral beam (VSB) is generated based on the competition mechanism between the self-focusing property of ring Airy beam and metalens phase distribution, which exhibits twisted properties and optical bottle structure along the propagation direction. The number of spiral lobes, rotation direction, shape and magnification times on the cross section of the proposed beam can be customized by flexibly tuning diffraction distance, topological charge and constant parameter. Therefore, the VSB can be viewed as tunable three-dimensional (3D) spiral beam, and our scheme has the superiority with more diverse and tunable intensity distribution. The properties of intensity distribution variation depended on the propagation distance and topological charge are demonstrated convincingly by employing the Poynting vector intuitive presentation the energy flow. The VSBs with the aid of above-mentioned properties are beneficial for guiding microparticles along the designed spiral path and capturing multiple microparticles into the closed dark regions. Finally, the modulated spiral beams are implemented as tool for particle manipulation in the three dimensional space to demonstrate the advantages of the modulated spiral beam and we can observe the stable trapping of the particles.

The effect of enhanced heat transfer across metal-nonmetal interfaces subject to femtosecond laser irradiation.

The heat transfer across metal-nonmetal interfaces inevitably affects the femtosecond laser processing of thin metal films coated on nonmetal substrates. In the present work, a two-temperature model with a metal-nonmetal interface is employed to numerically investigate the heat transfer across a metal-nonmetal interface. A parallel-series thermal circuit is considered under the drastic electron-phonon nonequilibrium induced by femtosecond laser irradiation. The interfacial thermal resistance affects temporal evolutions of surface electron temperature and phonon temperature, as well as the optical response simulated by the Drude-Lorentz model. By inserting an interlayer and reducing the interfacial thermal resistance, the enhanced heat transfer across Au-Al2O3 and Au-Si interfaces is confirmed. More heat transfers from a metal to a nonmetal due to lower total interfacial thermal resistance, which reshapes the temperature distributions of metal-electrons, metal-phonons, and nonmetal-phonons. Consequently, the higher damage threshold of thin Au films and the lower sensitivity of damage threshold versus film thickness are determined. It implies that the heat transfer across metal-nonmetal interfaces is found to affect the transient thermal reflectivity detection and the repeatable femtosecond laser processing of thin metal films.

Crosstalk suppression for high-density traveling-wave MZM array based on static and dynamic combined analysis and circuit-level designs.

Electrical crosstalk severely degrades the performance of Mach-Zehnder modulator (MZM) array. However, conventional crosstalk suppression techniques incur losses of large amounts of chip area for signal isolation, which becomes a bottleneck of high-density electronic-photonic integrated circuit. In this paper, the electrical crosstalk of Traveling-Wave MZM array is originally analyzed with static and dynamic combined crosstalk coefficients. Circuit-level suppression techniques of differential dual-drive electrode schemes with tightly coupled electrode pairs and a virtual ground structure with full-matching termination circuit are investigated for noise-removing effects. Simulation results show that the dynamic electrical crosstalk coefficient between two adjacent modulators is reduced to below 1.5%, which is five times lower than the baseline. The electro-optical link measurements show that the BER is significantly reduced from 1E-3 to 1E-12 for multi-channel operation, which confirms the effectiveness of the crosstalk suppression techniques.

Rapidly accelerated development of neutralizing COVID-19 antibodies by reducing cell line and CMC development timelines.

Since the Coronavirus Disease 2019 (COVID-19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much-shortened timeline of 3-6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS-CoV-2-neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization  approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late-stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next-generation sequencing-based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID-19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic-related biologics development may innovate typical biologics development timelines and become a new standard in the industry.

Excitation of ultraviolet range Dirac-type plasmon resonance with an ultra-high Q-factor in the topological insulator Bi1.5Sb0.5Te1.8Se1.2 nanoshell.

Excitation of ultraviolet (UV) range plasmon resonance with high quality (Q)-factor has been significantly challenging in plasmonics because of inherent limitations in metals like Au and Ag. Herein, we theoretically investigated UV-visible range plasmons in the topological insulator Bi1.5Sb0.5Te1.8Se1.2 (BSTS) nanosphere and nanoshell. In contrast to broad linewidth plasmon absorptions in the BSTS nanospheres, an ultra-sharp absorption peak with the Q-factor as high as 52 is excited at UV frequencies in the BSTS nanoshells. This peak is attributed to Dirac-type plasmon resonance originating from massless Dirac carriers in surface states of the BSTS. Furthermore, a tunable plasmon wavelength of the resonance is demonstrated by varying geometrical parameters of the BSTS nanoshells. This may find applications in surface enhanced Raman spectroscopies, nanolasers and biosensors in the UV regions.

Molecular dynamics study on the diffusion process of AuAgCuNiPd high-entropy alloy metallurgy induced by pulsed laser heating.

As novel alloy materials with outstanding mechanical properties, high-entropy alloys have a wide range of promising applications. By establishing individual Au, Ag, Cu, Ni, and Pd nanolaminates with face-centered-cubic lattice structure arrangements, molecular dynamics simulation is carried out to track the diffusion process of AuAgCuNiPd high-entropy alloy metallurgy, which is induced by pulsed laser heating. The temperature, potential energy, and kinetic energy are analyzed to evaluate the metallurgy. The snapshots and atomic fractions are presented to show the mass transfer between metallic nanolaminates. The diffusion process is firstly observed 0.3 ns after the central point for pulsed laser heating (absorbed laser energy density at 7 kJ cm-3 and pulse duration of 0.5 ns). Meanwhile, the degrees of atomic activity for Au, Ag, Cu, Ni, and Pd are assessed by calculating the mean square displacement and diffusion coefficient. Ni has a slightly larger diffusion coefficient than the other four metallic elements. Moreover, after the central point of laser irradiation, the kinetic energy of the system reduces, while the potential energy increases, which relates to the transition from nanolaminates to high-entropy alloys. A critical absorbed laser energy density of 6 kJ cm-3 with a relative error of 8.3% for the generation of AuAgCuNiPd high-entropy alloys is found. The order of constituent nanolaminates configured with the earlier initiation of diffusion between atoms in the neighboring nanolaminates speeds up the metallurgy.

Interference femtosecond laser stamping of micro-grating structures and time-resolved observation of its dynamics.

Selective slicing on a 100 nm thick ZnO film deposited on a Si substrate is achieved by an interference femtosecond (fs) laser stamping. A micro-grating structure with a period of ∼5 µm is completely ablated by an energy-optimized single pulse in one step. The elemental mappings demonstrate complete slice removals of the irradiated areas from the substrate without impurities mixed into the thin film. A calculation of the energy transmitted to the substrate and the characterization of the ablated Si channels infer that the irradiated slices are detached from the substrate by the selective ablation of the thin film and the counterforce of the Si substrate. The temporal and spatial evolution of the grating formation is investigated through a pump-probe microscope using the white light continuum (WLC) as the illumination probe. It is found that the extinctive constructive fringes occur at a delay of 8 picosecond (ps) caused by the increase of electron density. The irradiated slices initially bulge at the delay of 10-12 ps, then subsequently swell until strong material ejections at 800 ps. This study provides an opportunity to advance the understanding of micro-grating fabrications and thin film removals on heterostructures using fs lasers.

Strongly Lewis Acidic Metal-Organic Frameworks for Continuous Flow Catalysis.

The synthesis of highly acidic metal-organic frameworks (MOFs) has attracted significant research interest in recent years. We report here the design of a strongly Lewis acidic MOF, ZrOTf-BTC, through two-step transformation of MOF-808 (Zr-BTC) secondary building units (SBUs). Zr-BTC was first treated with 1 M hydrochloric acid solution to afford ZrOH-BTC by replacing each bridging formate group with a pair of hydroxide and water groups. The resultant ZrOH-BTC was further treated with trimethylsilyl triflate (Me3SiOTf) to afford ZrOTf-BTC by taking advantage of the oxophilicity of the Me3Si group. Electron paramagnetic resonance spectra of Zr-bound superoxide and fluorescence spectra of Zr-bound N-methylacridone provided a quantitative measurement of Lewis acidity of ZrOTf-BTC with an energy splitting (ΔE) of 0.99 eV between the πx* and πy* orbitals, which is competitive to the homogeneous benchmark Sc(OTf)3. ZrOTf-BTC was shown to be a highly active solid Lewis acid catalyst for a broad range of important organic transformations under mild conditions, including Diels-Alder reaction, epoxide ring-opening reaction, Friedel-Crafts acylation, and alkene hydroalkoxylation reaction. The MOF catalyst outperformed Sc(OTf)3 in terms of both catalytic activity and catalyst lifetime. Moreover, we developed a ZrOTf-BTC@SiO2 composite as an efficient solid Lewis acid catalyst for continuous flow catalysis. The Zr centers in ZrOTf-BTC@SiO2 feature identical coordination environment to ZrOTf-BTC based on spectroscopic evidence. ZrOTf-BTC@SiO2 displayed exceptionally high turnover numbers (TONs) of 1700 for Diels-Alder reaction, 2700 for epoxide ring-opening reaction, and 326 for Friedel-Crafts acylation under flow conditions. We have thus created strongly Lewis acidic sites in MOFs via triflation and constructed the MOF@SiO2 composite for continuous flow catalysis of important organic transformations.

Site Isolation in Metal-Organic Frameworks Enables Novel Transition Metal Catalysis.

Comprising periodically repeating inorganic nodes and organic linkers, metal-organic frameworks (MOFs) represent a novel class of porous molecular solids with well-defined pores and channels. Over the past two decades, a large array of organic linkers have been combined with many inorganic nodes to afford a vast library of MOFs. The synthetic tunability of MOFs distinguishes them from traditional porous inorganic materials and has allowed the rational design of many interesting properties, such as porosity, chirality, and chemical functionality, for potential applications in diverse areas including gas storage and separation, catalysis, light harvesting, chiral separation, and chemical sensing. In particular, the molecular functionality and intrinsic porosity of MOFs have rendered them attractive candidates as porous single-site solid catalysts for a large number of organic transformations. MOF catalysts offer several advantages over their homogeneous counterparts, including enhanced stability, recyclability and reusability, and facile removal of the toxic catalyst components from the organic products. Additionally, the highly ordered nature of MOFs leads to the generation of single-site solid catalysts, allowing for precise characterization of the catalytic sites through X-ray diffraction, X-ray absorption, and other spectroscopic interrogations and facilitating the elucidation of reaction mechanisms. Thus, MOF catalysis represents a fertile research area that is expected to witness continued growth in the foreseeable future. In this Account, we present our recent research progress in developing ligand-supported single-site MOF catalysts for challenging organic reactions. We present two complementary approaches to the design of ligand-supported MOF catalysts: direct incorporation of prefunctionalized organic linkers into MOFs and postsynthetic functionalization of orthogonal secondary functional groups of the organic linkers in MOFs. Monophosphine-, bipyridine-, ß-diketimine-, and salicylaldimine-based ligands have been used to support both precious (Pd, Pt, Ir, Ru) and earth-abundant (Cu, Co, Fe) metals for a number of interesting catalytic reactions. The resulting MOF catalysts feature stable low-coordination species with minimum steric bulk around the active site-a feat that remains a challenge for homogeneous catalysts. For each ligand, we describe types of reactions catalyzed by the MOF in comparison with its homogeneous counterpart. In all cases, MOF catalysts outperformed their homogeneous counterparts in terms of catalyst stability, catalytic activity, and recyclability and reusability. Interestingly, several bipyridine- and salicylaldimine-ligated earth-abundant-metal-based MOF catalysts do not have homogeneous counterparts because the molecular compounds disproportionate or oligomerize to form inactive species in solution. This Account not only presents several interesting designs of ligand-supported single-site MOF catalysts but also provides illustrative examples of how site isolation in MOF catalysts shuts down deactivation pathways experienced by homogeneous systems. With precise knowledge of MOF structures and catalytically active sites, we envision the development of practically useful MOF catalysts comprising tailor-made building blocks that rationally optimize catalytic activities and selectivities.

Tuning Lewis Acidity of Metal-Organic Frameworks via Perfluorination of Bridging Ligands: Spectroscopic, Theoretical, and Catalytic Studies.

The Lewis acidity of metal-organic frameworks (MOFs) has attracted much research interest in recent years. We report here the development of two quantitative methods for determining the Lewis acidity of MOFs-based on electron paramagnetic resonance (EPR) spectroscopy of MOF-bound superoxide (O2•-) and fluorescence spectroscopy of MOF-bound N-methylacridone (NMA)-and a simple strategy that significantly enhances MOF Lewis acidity through ligand perfluorination. Two new perfluorinated MOFs, Zr6-fBDC and Zr6-fBPDC, where H2fBDC is 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylic acid and H2fBPDC is 2,2',3,3',5,5',6,6'-octafluoro-4,4'-biphenyldicarboxylic acid, were shown to be significantly more Lewis acidic than nonsubstituted UiO-66 and UiO-67 as well as the nitrated MOFs Zr6-BDC-NO2 and Zr6-BPDC-(NO2)2. Zr6-fBDC was shown to be a highly active single-site solid Lewis acid catalyst for Diels-Alder and arene C-H iodination reactions. Thus, this work establishes the important role of ligand perfluorination in enhancing MOF Lewis acidity and the potential of designing highly Lewis acidic MOFs for fine chemical synthesis.

Titanium(III)-Oxo Clusters in a Metal-Organic Framework Support Single-Site Co(II)-Hydride Catalysts for Arene Hydrogenation.

Titania (TiO2) is widely used in the chemical industry as an efficacious catalyst support, benefiting from its unique strong metal-support interaction. Many proposals have been made to rationalize this effect at the macroscopic level, yet the underlying molecular mechanism is not understood due to the presence of multiple catalytic species on the TiO2 surface. This challenge can be addressed with metal-organic frameworks (MOFs) featuring well-defined metal oxo/hydroxo clusters for supporting single-site catalysts. Herein we report that the Ti8(µ2-O)8(µ2-OH)4 node of the Ti-BDC MOF (MIL-125) provides a single-site model of the classical TiO2 support to enable CoII-hydride-catalyzed arene hydrogenation. The catalytic activity of the supported CoII-hydride is strongly dependent on the reduction of the Ti-oxo cluster, definitively proving the pivotal role of TiIII in the performance of the supported catalyst. This work thus provides a molecularly precise model of Ti-oxo clusters for understating the strong metal-support interaction of TiO2-supported heterogeneous catalysts.

Atomistic insights into the exothermic self-sustained alloying of Al-shell/Ni-core nanoparticle triggered by laser irradiation.

By imposing a picosecond laser pulse irradiation on an Al-shell/Ni-core nanoparticle, an exothermic self-sustained alloying is triggered. Molecular dynamics simulation is implemented to get atomistic insights into the alloying process. The nanoparticle is composed by an equiatomic number of Al atoms in the shell and Ni atoms in the core. Due to the absorption of laser energy from the surface of the nanoparticle, atomic motion becomes active. The inter-diffusion of Ni and Al atoms results in thermal energy generation. It is found that the incident laser energy is responsible for controlling the degree of self-heating of the nanoparticle by governing the potential energy change during the inter-diffusion of Al-shell and Ni-core atoms.

Trivalent Zirconium and Hafnium Metal-Organic Frameworks for Catalytic 1,4-Dearomative Additions of Pyridines and Quinolines.

We report the quantitative conversion of [MIV6(µ3-O)4(µ3-OH)4Cl12]6- nodes in the MCl2-BTC metal-organic framework into the [MIII6(µ3-O)4(µ3-ONa)4H6]6- nodes in MIIIH-BTC (M = Zr, Hf; BTC is 1,3,5-benzenetricarboxylate) via bimetallic reductive elimination of H2 from putative [MIV6(µ3-O)4(µ3-OH)4H12]6- nodes. The coordinatively unsaturated MIIIH centers in MIIIH-BTC are highly active and selective for 1,4-dearomative hydroboration and hydrosilylation of pyridines and quinolines. This work demonstrated the potential of secondary building unit transformation in generating electronically unique and homogeneously inaccessible single-site solid catalysts for organic synthesis.

Confinement of Ultrasmall Cu/ZnOx Nanoparticles in Metal-Organic Frameworks for Selective Methanol Synthesis from Catalytic Hydrogenation of CO2.

The interfaces of Cu/ZnO and Cu/ZrO2 play vital roles in the hydrogenation of CO2 to methanol by these composite catalysts. Surface structural reorganization and particle growth during catalysis deleteriously reduce these active interfaces, diminishing both catalytic activities and MeOH selectivities. Here we report the use of preassembled bpy and Zr6(µ3-O)4(µ3-OH)4 sites in UiO-bpy metal-organic frameworks (MOFs) to anchor ultrasmall Cu/ZnOx nanoparticles, thus preventing the agglomeration of Cu NPs and phase separation between Cu and ZnOx in MOF-cavity-confined Cu/ZnOx nanoparticles. The resultant Cu/ZnOx@MOF catalysts show very high activity with a space-time yield of up to 2.59 gMeOH kgCu-1 h-1, 100% selectivity for CO2 hydrogenation to methanol, and high stability over 100 h. These new types of strong metal-support interactions between metallic nanoparticles and organic chelates/metal-oxo clusters offer new opportunities in fine-tuning catalytic activities and selectivities of metal nanoparticles@MOFs.

Single-Site Cobalt Catalysts at New Zr12(µ3-O)8(µ3-OH)8(µ2-OH)6 Metal-Organic Framework Nodes for Highly Active Hydrogenation of Nitroarenes, Nitriles, and Isocyanides.

We report here the synthesis of a robust and porous metal-organic framework (MOF), Zr12-TPDC, constructed from triphenyldicarboxylic acid (H2TPDC) and an unprecedented Zr12 secondary building unit (SBU): Zr12(µ3-O)8(µ3-OH)8(µ2-OH)6. The Zr12-SBU can be viewed as an inorganic node dimerized from two commonly observed Zr6 clusters via six µ2-OH groups. The metalation of Zr12-TPDC SBUs with CoCl2 followed by treatment with NaBEt3H afforded a highly active and reusable solid Zr12-TPDC-Co catalyst for the hydrogenation of nitroarenes, nitriles, and isocyanides to corresponding amines with excellent activity and selectivity. This work highlights the opportunity in designing novel MOF-supported single-site solid catalysts by tuning the electronic and steric properties of the SBUs.

Transformation of Metal-Organic Framework Secondary Building Units into Hexanuclear Zr-Alkyl Catalysts for Ethylene Polymerization.

We report the stepwise and quantitative transformation of the Zr6(µ3-O)4(µ3-OH)4(HCO2)6 nodes in Zr-BTC (MOF-808) to the [Zr6(µ3-O)4(µ3-OH)4Cl12]6- nodes in ZrCl2-BTC, and then to the organometallic [Zr6(µ3-O)4(µ3-OLi)4R12]6- nodes in ZrR2-BTC (R = CH2SiMe3 or Me). Activation of ZrCl2-BTC with MMAO-12 generates ZrMe-BTC, which is an efficient catalyst for ethylene polymerization. ZrMe-BTC displays unusual electronic and steric properties compared to homogeneous Zr catalysts, possesses multimetallic active sites, and produces high-molecular-weight linear polyethylene. Metal-organic framework nodes can thus be directly transformed into novel single-site solid organometallic catalysts without homogeneous analogs for polymerization reactions.

Phenanthroline-based metal-organic frameworks for Fe-catalyzed Csp3-H amination.

We report here the synthesis of a robust and highly porous Fe-phenanthroline-based metal-organic framework (MOF) and its application in catalyzing challenging inter- and intramolecular C-H amination reactions. For the intermolecular amination reactions, a FeBr2-metalated MOF selectively functionalized secondary benzylic and allylic C-H bonds. The intramolecular amination reactions utilizing organic azides as the nitrene source required the reduction of the FeBr2-metalated MOF with NaBHEt3 to generate the active catalyst. For both reactions, Fe or Zr leaching was less than 0.1%, and MOFs could be recycled and reused with no loss in catalytic activity. Furthermore, MOF catalysts were significantly more active than the corresponding homogeneous analogs. This work demonstrates the great potential of MOFs in generating highly active, recyclable, and reusable earth abundant metal catalysts for challenging organic transformations.