Unlocking the secrets of porous silicon formation: insights into magnesiothermic reduction mechanism using in situ powder X-ray diffraction studies.

The magnesiothermic reduction of SiO2 is an important reaction as it is a bulk method that produces porous Si for a wide range of applications directly from SiO2. While its main advantage is potential tunability, the reaction behavior and final product properties are heavily dependent on many parameters including feedstock type. However, a complete understanding of the reaction pathway has not yet been achieved. Here, using in situ X-ray diffraction analysis, for the first time, various pathways through which the magnesiothermic reduction reaction proceeds were mapped. Further, the key parameters and conditions that determine which pathways are favored were determined. It was discovered that the reaction onset temperatures can be as low as 348 ± 7 °C, which is significantly lower when compared to previously reported values. The onset temperature is dependent on the size of Mg particles used in the reaction. Further, Mg2Si was identified as a key intermediate rather than a reaction byproduct during the reduction process. Its rate of consumption is determined by the reaction temperature which needs to be >561 °C. These findings can enable process and product optimization of the magnesiothermic reduction process to manufacture and tune porous Si for a range of applications.

Meniscus Allograft Transplantation in Conjunction With Arthroscopic Biologic Knee Restoration Delays Arthroplasty in Patients Older Than 50 Years.

PURPOSE: To evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years previously advised joint arthroplasty. METHODS: A total of 108 meniscus allograft transplants using the arthroscopic 3-tunnel technique between 1997 and 2019 in patients older than 50 years were retrospectively reviewed with a 2-year minimum follow-up period. Inclusion criteria were patients recommended for knee arthroplasty with pain and preservation of some joint space by standing flexion radiographs. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol, and failure to complete research questionnaires. International Knee Documentation Committee composite and isolated pain scale were evaluated longitudinally. Time from meniscus allograft transplant to arthroplasty was measured, with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain. RESULTS: Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (P < .001) in pain and function as assessed by International Knee Documentation Committee Score. These improvements were sustained 10 years postoperatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference through 10 years postoperatively. CONCLUSIONS: Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates older than 50 years. Influences of concomitant procedures cannot be defined. LEVEL OF EVIDENCE: Level IV, therapeutic case series, retrospective.

'I was going into it blind': Nearest Relatives, legal literacy, and the Mental Health Act 1983.

Eligible relatives are given rights and powers in the compulsory treatment of people with mental health problems in several international jurisdictions, including within England and Wales. However, little attention has been given to whether relatives feel legally literate or competent to fulfil such roles. This article examines this issue through focussing on the experiences of Nearest Relatives, who are given rights and powers during Mental Health Act 1983 (MHA) assessments for compulsory admission in England and Wales. Interviews with nineteen Nearest Relatives in England were conducted and were thematically analysed. Three themes were identified. First, NRs spoke about their awareness and knowledge of the role. They predominantly reported negative experiences in which they received no or little information. They also reported that professionals assumed they possessed legal knowledge, and their legal knowledge was largely self-taught. Secondly, NRs reported uncertainty about their own rights and powers, noting the role lacked status or informational or emotional support. Third, NRs highlighted areas for legal reform, stating that the NR role was important, but required specialist support systems for NRs. The findings of this study indicate greater attention needs to be given by law and policy makers to support relatives' understanding of their rights and powers under the MHA, if the NR role is to be effective in helping to safeguard patient rights under the European Convention on Human Rights. These include the right in Article 5 not to be arbitrarily deprived of one's liberty and the right to a private and family life in Article 8. Legislators also need to take account of these factors when considering proposals to reform mental health law in England and Wales.

Polaron absorption in aligned conjugated polymer films: breakdown of adiabatic treatments and going beyond the conventional mid-gap state model.

This study provides the first experimental polarized intermolecular and intramolecular optical absorption components of field-induced polarons in regioregular poly(3-hexylthiophene-2,5-diyl), rr-P3HT, a polymer semiconductor. Highly aligned rr-P3HT thin films were prepared by a high temperature shear-alignment process that orients polymer backbones along the shearing direction. rr-P3HT in-plane molecular orientation was measured by electron diffraction, and out-of-plane orientation was measured through series of synchrotron X-ray scattering techniques. Then, with molecular orientation quantified, polarized charge modulation spectroscopy was used to probe mid-IR polaron absorption in the ℏω = 0.075 - 0.75 eV range and unambiguously assign intermolecular and intramolecular optical absorption components of hole polarons in rr-P3HT. This data represents the first experimental quantification of these polarized components and allowed long-standing theoretical predictions to be compared to experimental results. The experimental data is discrepant with predictions of polaron absorption based on an adiabatic framework that works under the Born-Oppenheimer approximation, but the data is entirely consistent with a more recent nonadiabatic treatment of absorption based on a modified Holstein Hamiltonian. This nonadiabatic treatment was used to show that both intermolecular and intramolecular polaron coherence break down at length scales significantly smaller than estimated structural coherence in either direction. This strongly suggests that polaron delocalization is fundamentally limited by energetic disorder in rr-P3HT.

Solution Shearing of Zirconium (Zr)-Based Metal-Organic Frameworks NU-901 and MOF-525 Thin Films for Electrocatalytic Reduction Applications.

Solution shearing, a meniscus-guided coating process, can create large-area metal-organic framework (MOF) thin films rapidly, which can lead to the formation of uniform membranes for separations or thin films for sensing and catalysis applications. Although previous work has shown that solution shearing can render MOF thin films, examples have been limited to a few prototypical systems, such as HKUST-1, Cu-HHTP, and UiO-66. Here, we expand on the applicability of solution shearing by making thin films of NU-901, a zirconium-based MOF. We study how the NU-901 thin film properties (i.e., crystallinity, surface coverage, and thickness) can be controlled as a function of substrate temperature and linker concentration. High fractional surface coverage of small-area (∼1 cm2) NU-901 thin films (0.88 ± 0.06) is achieved on a glass substrate for all conditions after one blade pass, while a low to moderate fractional surface coverage (0.73 ± 0.18) is obtained for large-area (∼5 cm2) NU-901 thin films. The crystallinity of NU-901 crystals increases with temperature and decreases with linker concentration. On the other hand, the adjusted thickness of NU-901 thin films increases with both increasing temperature and linker concentration. We also extend the solution shearing technique to synthesize MOF-525 thin films on a transparent conductive oxide that are useful for electrocatalysis. We show that Fe-metalated MOF-525 films can reduce CO2 to CO, which has implications for CO2 capture and utilization. The demonstration of thin film formation of NU-901 and MOF-525 using solution shearing on a wide range of substrates will be highly useful for implementing these MOFs in sensing and catalytic applications.

Remote and automated high-throughput powder diffraction measurements enabled by a robotic sample changer at SSRL beamline 2-1.

The general-purpose powder diffractometer beamline (BL2-1) at the Stanford Synchrotron Radiation Lightsource (SSRL) is described. The evolution of design and performance of BL2-1 are presented, in addition to current operating specifications, applications and measurement capabilities. Recent developments involve a robotic sample changer enabling high-throughput X-ray diffraction measurements, applicable to mail-in and remote operations. In situ and operando capabilities to measure samples with different form factors (e.g. capillary, flat plate or thin film, and transmission) and under variable experimental conditions are discussed. Several example datasets and accompanying Rietveld refinements are presented.

The United Nations Convention on the Rights of Persons with Disabilities and Social Work: Evidence for Impact?

The United Nations Convention on the Rights of Persons with Disabilities (hereafter CRPD) has provided a radical imperative for the reform of mental health and capacity legislation around the world. The interpretation of the CRPD has been controversial, ranging from the complete abolition of detention, forcible treatment, and substitute decision-making to accepting that elements of these measures need to be retained based on non-discriminatory criteria, additional safeguards, and a comprehensive shift towards supported decision-making. While the potential effects of the CRPD on mental health social work and social work generally are considerable given their shared commitment towards social justice, to date there has been no review of research evidence exploring their relationship. In addressing this knowledge gap, this study held a preliminary discussion with practitioners and academics at the European Association of Social Work Mental Health Special Interest Group in Amsterdam 2022, followed by a scoping literature review on the question: What impact, if any, has the CRPD had on social work practice? The review produced four main findings: impact on legislation; positive impact on practice; limited impact on practice; and impact on social work education and research. In sum, while there were some positive indications of social work and mental health social work practice being influenced by the CRPD, these were scant. Barriers to change included tendencies among some social workers to practise substitute decision-making, in part related to resourcing and policy contexts, and understandings of disability aligned to individualised/medical rather than social perspectives. The results indicate that legal reform on its own is insufficient to impact social work practice, and that realising the potential of the CRPD will necessitate good quality training, as well as improving social workers' knowledge of the human rights of people with mental impairment.

Xenograft bone-patellar tendon-bone ACL reconstruction: a case series at 20-year follow-up as proof of principle.

PURPOSE: ACL reconstruction has a significant failure rate. To address the need for inexpensive strong tissue, a treatment process to "humanize" porcine tissue was developed and tested in primates and humans. This report describes the long-term outcomes from the first human clinical trial using a porcine xenograft ACL reconstruction device. METHODS: The study was performed with Z-Lig™ xenograft ACL device in 2003 as a pilot clinical feasibility study. This device was processed to slow its immune-mediated destruction by enzymatic elimination of α-gal epitopes and by partial crosslinking to slow the infiltration of macrophages into the biotransplant. RESULTS: Ten patients underwent reconstruction with the Z-Lig™ device. Five of 10 patients failed due to subsequent trauma (n = 3), arthrofibrosis (n = 1), and surgical technical error (n = 1). One patient was lost to follow-up after the 12-year evaluation. Each remaining patient reported a stable fully athletic knee. Physical exams are consistent with a score of less than one on the ACL stability tests. MRIs demonstrate mature remodeling of the device. There is no significant degradation in patient-reported outcome scores, physical exams, or MRI appearance from 12 to 20-year follow-ups. CONCLUSIONS: The studies in a small group of patients have demonstrated that implantation of porcine ligament bioprosthesis into patients with torn ACLs can result in the reconstruction of the bioprosthesis into autologous ACL that remains successful over 20 years. The possibility of humanizing porcine tissue opens the door to unlimited clinical material for tissue reconstructions if supported by additional clinical trials. LEVEL OF EVIDENCE: IV, case series.

Development of a versatile electrochemical cell for in situ grazing-incidence X-ray diffraction during non-aqueous electrochemical nitrogen reduction.

In situ techniques are essential to understanding the behavior of electrocatalysts under operating conditions. When employed, in situ synchrotron grazing-incidence X-ray diffraction (GI-XRD) can provide time-resolved structural information of materials formed at the electrode surface. In situ cells, however, often require epoxy resins to secure electrodes, do not enable electrolyte flow, or exhibit limited chemical compatibility, hindering the study of non-aqueous electrochemical systems. Here, a versatile electrochemical cell for air-free in situ synchrotron GI-XRD during non-aqueous Li-mediated electrochemical N2 reduction (Li-N2R) has been designed. This cell not only fulfills the stringent material requirements necessary to study this system but is also readily extendable to other electrochemical systems. Under conditions relevant to non-aqueous Li-N2R, the formation of Li metal, LiOH and Li2O as well as a peak consistent with the α-phase of Li3N was observed, thus demonstrating the functionality of this cell toward developing a mechanistic understanding of complicated electrochemical systems.

Formation of Ba3Nb0.75Mn2.25O9-6H during thermo-chemical reduction of Ba4NbMn3O12-12R.

The resurgence of inter-est in hydrogen-related technologies has stimulated new studies aimed at advancing lesser-developed water-splitting processes, such as solar thermochemical hydrogen production (STCH). Progress in STCH has been largely hindered by a lack of new materials able to efficiently split water at a rate comparable to ceria under identical experimental conditions. BaCe0.25Mn0.75O3 (BCM) recently demonstrated enhanced hydrogen production over ceria and has the potential to further our understanding of two-step thermochemical cycles. A significant feature of the 12R hexa-gonal perovskite structure of BCM is the tendency to, in part, form a 6H polytype at high temperatures and reducing environments (i.e., during the first step of the thermochemical cycle), which may serve to mitigate degradation of the complex oxide. An analogous compound, namely BaNb0.25Mn0.75O3 (BNM) with a 12R structure was synthesized and displays nearly complete conversion to the 6H structure under identical reaction conditions as BCM. The structure of the BNM-6H polytype was determined from Rietveld refinement of synchrotron powder X-ray diffraction data and is presented within the context of the previously established BCM-6H structure.

Role of aggregates and microstructure of mixed-ionic-electronic-conductors on charge transport in electrochemical transistors.

Synthetic efforts have delivered a library of organic mixed ionic-electronic conductors (OMIECs) with high performance in electrochemical transistors. The most promising materials are redox-active conjugated polymers with hydrophilic side chains that reach high transconductances in aqueous electrolytes due to volumetric electrochemical charging. Current approaches to improve transconductance and device stability focus mostly on materials chemistry including backbone and side chain design. However, other parameters such as the initial microstructure and microstructural rearrangements during electrochemical charging are equally important and are influenced by backbone and side chain chemistry. In this study, we employ a polymer system to investigate the fundamental electrochemical charging mechanisms of OMIECs. We couple in situ electronic charge transport measurements and spectroelectrochemistry with ex situ X-ray scattering electrochemical charging experiments and find that polymer chains planarize during electrochemical charging. Our work shows that the most effective conductivity modulation is related to electrochemical accessibility of well-ordered, interconnected aggregates that host high mobility electronic charge carriers. Electrochemical stress cycling induces microstructural changes, but we find that these aggregates can largely maintain order, providing insights on the structural stability and reversibility of electrochemical charging in these systems. This work shows the importance of material design for creating OMIECs that undergo structural rearrangements to accommodate ions and electronic charge carriers during which percolating networks are formed for efficient electronic charge transport.

Electrochemical Recycling of Adenosine Triphosphate in Biocatalytic Reaction Cascades.

Adenosine triphosphate (ATP) provides the driving force necessary for critical biological functions in all living organisms. In synthetic biocatalytic reactions, this cofactor is recycled in situ using high-energy stoichiometric reagents, an approach that generates waste and poses challenges with enzyme stability. On the other hand, an electrochemical recycling system would use electrons as a convenient source of energy. We report a method that uses electricity to turn over enzymes for ATP generation in a simplified cellular respiration mimic. The method is simple, robust, and scalable, as well as broadly applicable to complex enzymatic processes including a four-enzyme biocatalytic cascade in the synthesis of the antiviral molnupiravir.

Scalable Synthesis and Characterization of Multilayer γ-Graphyne, New Carbon Crystals with a Small Direct Band Gap.

γ-Graphyne is the most symmetric sp2/sp1 allotrope of carbon, which can be viewed as graphene uniformly expanded through the insertion of two-carbon acetylenic units between all the aromatic rings. To date, synthesis of bulk γ-graphyne has remained a challenge. We here report the synthesis of multilayer γ-graphyne through crystallization-assisted irreversible cross-coupling polymerization. A comprehensive characterization of this new carbon phase is described, including synchrotron powder X-ray diffraction, electron diffraction, lateral force microscopy, Raman spectroscopy, infrared spectroscopy, and cyclic voltammetry. Experiments indicate that γ-graphyne is a 0.48 eV band gap semiconductor, with a hexagonal a-axis spacing of 6.88 Å and an interlayer spacing of 3.48 Å, which is consistent with theoretical predictions. The observed crystal structure has an aperiodic sheet stacking. The material is thermally stable up to 240 °C but undergoes transformation at higher temperatures. While conventional 2D polymerization and reticular chemistry rely on error correction through reversibility, we demonstrate that a periodic covalent lattice can be synthesized under purely kinetic control. The reported methodology is scalable and inspires extension to other allotropes of the graphyne family.

Formation Mechanism of Flower-like Polyacrylonitrile Particles.

Flower-like polyacrylonitrile (PAN) particles have shown promising performance for numerous applications, including sensors, catalysis, and energy storage. However, the detailed formation process of these unique structures during polymerization has not been investigated. Here, we elucidate the formation process of flower-like PAN particles through a series of in situ and ex situ experiments. We have the following key findings. First, lamellar petals within the flower-like particles were predominantly orthorhombic PAN crystals. Second, branching of the lamellae during the particle formation arose from PAN's fast nucleation and growth on pre-existing PAN crystals, which was driven by the poor solubility of PAN in the reaction solvent. Third, the particles were formed to maintain a constant center-to-center distance during the reaction. The separation distance was attributed to strong electrostatic repulsion, which resulted in the final particles' spherical shape and uniform size. Lastly, we employed the understanding of the formation mechanism to tune the PAN particles' morphology using several experimental parameters including incorporating comonomers, changing temperature, adding nucleation seeds, and adjusting the monomer concentration. These findings provide important insights into the bottom-up design of advanced nanostructured PAN-based materials and controlled polymer nanostructure self-assemblies.

Development of an operando characterization stage for multi-modal synchrotron x-ray experiments.

It is widely accepted that micro- and nanoscale inhomogeneities govern the performance of many thin-film solar cell absorbers. These inhomogeneities yield material properties (e.g., composition, structure, and charge collection) that are challenging to correlate across length scales and measurement modalities. The challenge is compounded if a correlation is sought during device operation or in conditions that mimic aging under particular stressors (e.g., heat and electrical bias). Correlative approaches, particularly those based on synchrotron x-ray sources, are powerful since they can access several material properties in different modes (e.g., fluorescence, diffraction, and absorption) with minimal sample preparation. Small-scale laboratory x-ray instruments have begun to offer multi-modality but are typically limited by low x-ray photon flux, low spatial resolution, or specific sample sizes. To overcome these limitations, a characterization stage was developed to enable multi-scale, multi-modal operando measurements of industrially relevant photovoltaic devices. The stage offers compatibility across synchrotron x-ray facilities, enabling correlation between nanoscale x-ray fluorescence microscopy, microscale x-ray diffraction microscopy, and x-ray beam induced current microscopy, among others. The stage can accommodate device sizes up to 25 × 25 mm2, offering access to multiple regions of interest and increasing the statistical significance of correlated properties. The stage materials can sustain humid and non-oxidizing atmospheres, and temperature ranges encountered by photovoltaic devices in operational environments (e.g., from 25 to 100 °C). As a case study, we discuss the functionality of the stage by studying Se-alloyed CdTe photovoltaic devices aged in the stage between 25 and 100 °C.

Accurately Quantifying Stress during Metal Halide Perovskite Thin Film Formation.

The role of strain in metal halide perovskite (MHP) solar cells is still under investigation, showing both beneficial and detrimental effects on the device performance and stability. One crucial component to elucidating the impact of strain in the MHP absorber is a robust method of quantifying the amount of strain in the material. Here, we present a parametric refinement approach based on grazing incidence wide-angle X-ray scattering and demonstrate its use on quantifying strain during thermal annealing and subsequent cooling as a function of substrate and processing route. We use the analysis to reveal the impact of the cubic-to-tetragonal phase transition during cooling on the material's strain and discuss texture formation as a potential strain-relief mechanism. Thereby we present both a robust approach to quantify strain in MHPs and potential mechanisms to control strain in the film, opening the path for further investigations of strain in MHPs.

A laser powder bed fusion system for operando synchrotron x-ray imaging and correlative diagnostic experiments at the Stanford Synchrotron Radiation Lightsource.

Laser powder bed fusion (LPBF) is a highly dynamic multi-physics process used for the additive manufacturing (AM) of metal components. Improving process understanding and validating predictive computational models require high-fidelity diagnostics capable of capturing data in challenging environments. Synchrotron x-ray techniques play a vital role in the validation process as they are the only in situ diagnostic capable of imaging sub-surface melt pool dynamics and microstructure evolution during LPBF-AM. In this article, a laboratory scale system designed to mimic LPBF process conditions while operating at a synchrotron facility is described. The system is implemented with process accurate atmospheric conditions, including an air knife for active vapor plume removal. Significantly, the chamber also incorporates a diagnostic sensor suite that monitors emitted optical, acoustic, and electronic signals during laser processing with coincident x-ray imaging. The addition of the sensor suite enables validation of these industrially compatible single point sensors by detecting pore formation and spatter events and directly correlating the events with changes in the detected signal. Experiments in the Ti-6Al-4V alloy performed at the Stanford Synchrotron Radiation Lightsource using the system are detailed with sufficient sampling rates to probe melt pool dynamics. X-ray imaging captures melt pool dynamics at frame rates of 20 kHz with a 2 µm pixel resolution, and the coincident diagnostic sensor data are recorded at 470 kHz. This work shows that the current system enables the in situ detection of defects during the LPBF process and permits direct correlation of diagnostic signatures at the exact time of defect formation.

Formation of 6H-Ba3Ce0.75Mn2.25O9 during Thermochemical Reduction of 12R-Ba4CeMn3O12: Identification of a Polytype in the Ba(Ce,Mn)O3 Family.

The resurgence of interest in a hydrogen economy and the development of hydrogen-related technologies has initiated numerous research and development efforts aimed at making the generation, storage, and transportation of hydrogen more efficient and affordable. Solar thermochemical hydrogen production (STCH) is a process that potentially exhibits numerous benefits such as high reaction efficiencies, tunable thermodynamics, and continued performance over extended cycling. Although CeO2 has been the de facto standard STCH material for many years, more recently 12R-Ba4CeMn3O12 (BCM) has demonstrated enhanced hydrogen production at intermediate H2/H2O conditions compared to CeO2, making it a contender for large-scale hydrogen production. However, the thermo-reduction stability of 12R-BCM dictates the oxygen partial pressure (pO2) and temperature conditions optimal for cycling. In this study, we identify the formation of a 6H-BCM polytype at high temperature and reducing conditions, experimentally and computationally, as a mechanism and pathway for 12R-BCM decomposition. 12R-BCM was synthesized with high purity and then controllably reduced using thermogravimetric analysis (TGA). Synchrotron X-ray diffraction (XRD) data is used to identify the formation of a 6H-Ba3Ce0.75Mn2.25O9 (6H-BCM) polytype that is formed at 1350 °C under strongly reducing pO2. Density functional theory (DFT) total energy and defect calculations show a window of thermodynamic stability for the 6H-polytype consistent with the XRD results. These data provide the first evidence of the 6H-BCM polytype and could provide a mechanistic explanation for the superior water-splitting behaviors of 12R-BCM.

Catalytic Performance and Near-Surface X-ray Characterization of Titanium Hydride Electrodes for the Electrochemical Nitrate Reduction Reaction.

The electrochemical nitrate reduction reaction (NO3RR) on titanium introduces significant surface reconstruction and forms titanium hydride (TiHx, 0 < x ≤ 2). With ex situ grazing-incidence X-ray diffraction (GIXRD) and X-ray absorption spectroscopy (XAS), we demonstrated near-surface TiH2 enrichment with increasing NO3RR applied potential and duration. This quantitative relationship facilitated electrochemical treatment of Ti to form TiH2/Ti electrodes for use in NO3RR, thereby decoupling hydride formation from NO3RR performance. A wide range of NO3RR activity and selectivity on TiH2/Ti electrodes between -0.4 and -1.0 VRHE was observed and analyzed with density functional theory (DFT) calculations on TiH2(111). This work underscores the importance of relating NO3RR performance with near-surface electrode structure to advance catalyst design and operation.

A kinase-cGAS cascade to synthesize a therapeutic STING activator.

The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence1-3. Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents4,5. Here we describe the discovery and construction of an enzymatic cascade to MK-1454, a highly potent stimulator of interferon genes (STING) activator under study as an immuno-oncology therapeutic6,7 (ClinicalTrials.gov study NCT04220866 ). From two non-natural nucleotide monothiophosphates, MK-1454 is assembled diastereoselectively in a one-pot cascade, in which two thiotriphosphate nucleotides are simultaneously generated biocatalytically, followed by coupling and cyclization catalysed by an engineered animal cyclic guanosine-adenosine synthase (cGAS). For the thiotriphosphate synthesis, three kinase enzymes were engineered to develop a non-natural cofactor recycling system in which one thiotriphosphate serves as a cofactor in its own synthesis. This study demonstrates the substantial capacity that currently exists to use biosynthetic approaches to discover and manufacture complex, non-natural molecules.