Recent Findings Research Articles

Enhancing probiotic impact: engineering Saccharomyces boulardii for optimal acetic acid production and gastric passage tolerance.

Saccharomyces boulardii has been a subject of growing interest due to its potential as a probiotic microorganism with applications in gastrointestinal health, but the molecular cause for its probiotic potency has remained elusive. The recent discovery that S. boulardii contains unique mutations causing high acetic acid accumulation and inhibition of bacterial growth provides a possible clue. The natural S. boulardii isolates Sb.P and Sb.A are homozygous for the recessive mutation whi2S270* and accumulate unusually high amounts of acetic acid, which strongly inhibit bacterial growth. However, the homozygous whi2S270* mutation also leads to acetic acid sensitivity and acid sensitivity in general. In the present study, we have constructed a new S. boulardii strain, derived from the widely therapeutically used CMCN I-745 strain (isolated from the pharmaceutical product Enterol), producing even higher levels of acetic acid while keeping the same tolerance toward low pH as the parent Enterol (ENT) strain. This newly engineered strain, named ENT3, has a homozygous deletion of ACH1 and strong overexpression of ALD4. It is also able to accumulate much higher acetic acid concentrations when growing on low glucose levels, in contrast to the ENT wild-type and Sb.P strains. Moreover, we show the antimicrobial capacity of ENT3 against gut pathogens in vitro and observed that higher acetic acid production might correlate with better persistence in the gut in healthy mice. These findings underscore the possible role of the unique acetic acid production and its potential for improvement of the probiotic action of S. boulardii.IMPORTANCESuperior variants of the probiotic yeast Saccharomyces boulardii produce high levels of acetic acid, which inhibit the growth of bacterial pathogens. However, these strains also show increased acid sensitivity, which can compromise the viability of the cells during their passage through the stomach. In this work, we have developed by genetic engineering a variant of Saccharomyces boulardii that produces even higher levels of acetic acid and does not show enhanced acid sensitivity. We also show that the S. boulardii yeasts with higher acetic acid production persist longer in the gut, in agreement with a previous work indicating competition between probiotic yeast and bacteria for residence in the gut.

Genetic regulation of m6A RNA methylation and its contribution in human complex diseases.

N6-methyladenosine (m6A) has been established as the most prevalent chemical modification in message RNA (mRNA), playing an essential role in determining the fate of RNA molecules. Dysregulation of m6A has been revealed to lead to abnormal physiological conditions and cause various types of human diseases. Recent studies have delineated the genetic regulatory maps for m6A methylation by mapping the quantitative trait loci of m6A (m6A-QTLs), thereby building up the regulatory circuits linking genetic variants, m6A, and human complex traits. Here, we review the recent discoveries concerning the genetic regulatory maps of m6A, describing the methodological and technical details of m6A-QTL identification, and introducing the key findings of the cis- and trans-acting drivers of m6A. We further delve into the tissue- and ethnicity-specificity of m6A-QTL, the association with other molecular phenotypes in light of genetic regulation, the regulators underlying m6A genetics, and importantly, the functional roles of m6A in mediating human complex diseases. Lastly, we discuss potential research avenues that can accelerate the translation of m6A genetics studies toward the development of therapies for human genetic diseases.

Long-Term Energy System Modelling for a Clean Energy Transition in Egypt’s Energy Sector

Egypt has the potential to generate a significant amount of energy from renewable technologies, in particular solar PV, concentrated solar power (CSP), and onshore and offshore wind. The energy sector is reliant on fossil fuels, particularly natural gas, for electricity production and is at risk of locking itself into a high carbon pathway. Globally, reducing greenhouse gas (GHG) emissions associated with national energy sectors is a target outlined in the UN’s Paris Agreement. To reduce carbon dioxide (CO2) emissions associated with a higher dependence on fossil fuels, Egypt must consider upscaling renewable energy technologies (RETs) to achieve a clean energy transition (CET). This research modelled six scenarios using clicSAND for OSeMOSYS to identify the technologies and policy target improvements that are needed to upscale RETs within Egypt’s energy sector. The results showed that solar PV and onshore wind are key technologies to be upscaled to contribute towards Egypt’s CET. The optimal renewable target is the International Renewable Energy Agency’s (IRENA) target of 53% of electricity being sourced from RETs by 2030, which will cost USD 16.4 billion more up to 2035 than Egypt’s current Integrated Sustainable Energy Strategy (ISES) target of 42% by 2035; it also saves 732.0 MtCO2 over the entire modelling period to 2070. Socio-economic barriers to this transition are considered, such as recent discoveries of natural gas reserves combined with a history of energy insecurity, political instability impacting investor confidence, and a lack of international climate funding. The paper concludes with policy recommendations that would enable Egypt to progress towards achieving a CET.

Optogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation.

Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear. Here we measured brain-wide responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7 T scanner and a cryoprobe. Transient activation of DRN serotonin neurons caused brain-wide activation, including the medial prefrontal cortex, the striatum, and the ventral tegmental area. The same stimulation under anesthesia with isoflurane decreased brain-wide activation, including the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 receptors. Together, these results provide insight into the DR serotonergic system, which is consistent with recent discoveries of its functions in adaptive behaviors.

Depth‐resolved historical painting study with minimal microsampling, illustrated with a newly discovered Botticelli workshop painting

AbstractA painting from the Botticelli workshop has been studied after its recent discovery, with an innovative and noninvasive approach combining two‐ dimensional scanning macro‐x‐ray fluorescence imaging (MA‐XRF) and a laboratory‐based depth‐resolved site‐selective confocal micro‐x‐ray fluorescence (CXRF) device. These analyses were supported by measurements on cross‐sections taken from the artwork using scanning electron microscopy coupled with an energy‐dispersive x‐ray system. The aims of this study are to confirm the painting's attribution and authentication, find characteristic markers and features, understand the artist's technique, materials used, and palette, and all of it while reducing sampling. The analyzing approach used combines imaging and site‐selective techniques while avoiding, reducing and replacing sampling without compromising the results. Chemical maps of the painting were obtained by MA‐XRF and enabled the identification of zones, colors, and chemical elements of interest alongside with a first assumption on the pigments used. Depth profiles were then performed in precise areas and colors using CXRF, allowing to evidence overlaying paint layers and obtain a more complete 3D vision of the painting. Contrasting the findings using this new methodology with the traditionally employed analysis process involving microsampling allowed us to determine the accuracy and veracity of our conclusions.

Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.

Cerebral small vessel disease (cSVD) encompasses a heterogeneous group of age-related small vessel pathologies that affect multiple regions. Disease manifestations range from lesions incidentally detected on neuroimaging (white matter hyperintensities, small deep infarcts, microbleeds, or enlarged perivascular spaces) to severe disability and cognitive impairment. cSVD accounts for approximately 25% of ischemic strokes and the vast majority of spontaneous intracerebral hemorrhage and is also the most important vascular contributor to dementia. Despite its high prevalence and potentially long therapeutic window, there are still no mechanism-based treatments. Here, we provide an overview of the recent advances in this field. We summarize recent data highlighting the remarkable continuum between monogenic and multifactorial cSVDs involving NOTCH3, HTRA1, and COL4A1/A2 genes. Taking a vessel-centric view, we discuss possible cause-and-effect relationships between risk factors, structural and functional vessel changes, and disease manifestations, underscoring some major knowledge gaps. Although endothelial dysfunction is rightly considered a central feature of cSVD, the contributions of smooth muscle cells, pericytes, and other perivascular cells warrant continued investigation.

Metabolic dependencies of acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy primarily driven by an immature population of AML cells termed leukemia stem cells (LSCs) that are implicated in AML development, chemoresistance, and relapse. An emerging area of research in AML focuses on identifying and targeting the aberrant metabolism in LSCs. Dysregulated metabolism is involved in sustaining functional properties of LSCs, impeding myeloid differentiation, and evading programmed cell death, both in the process of leukemogenesis and in response to chemotherapy. This review discusses recent discoveries regarding the aberrant metabolic processes of AML LSCs that have begun to change the therapeutic landscape of AML.

The speech neuroprosthesis.

Loss of speech after paralysis is devastating, but circumventing motor-pathway injury by directly decoding speech from intact cortical activity has the potential to restore naturalcommunication and self-expression. Recent discoveries have defined how key features of speech production are facilitated by the coordinated activity of vocal-tract articulatory and motor-planning cortical representations. In this Review, we highlight such progress and how it has led to successful speech decoding, first in individuals implanted with intracranial electrodes for clinicalepilepsy monitoringand subsequently in individuals with paralysis as part ofearlyfeasibility clinical trials to restore speech. We discuss high-spatiotemporal-resolution neural interfaces and the adaptation of state-of-the-art speech computational algorithms that have driven rapidandsubstantial progress indecoding neural activity into text, audible speech, and facial movements. Although restoring natural speech is a long-term goal, speech neuroprostheses already have performance levels that surpass communication rates offered by current assistive-communication technology. Given this accelerated rate of progress in the field, we propose key evaluation metrics for speed and accuracy, among others, to help standardize across studies. We finish by highlighting several directions to more fully explore the multidimensional feature space of speech and language, which will continue to accelerate progress towards a clinically viable speech neuroprosthesis.

Borrelia burgdorferi

Since its recent discovery in the late 1970s, Lyme Disease (LD) has been a growing public health concern, especially in the United States where it accounts for the majority of vector-borne infections each year. The causative agent, Borrelia burgdorferi, is transmitted to humans through the bite of an infected Ixodes tick. This pathogen uses many unique mechanisms to both shield itself from the host immune response and cause disease. Clinically, LD presents in successive phases, with each increasing in severity as the bacterial cells migrate to new tissues and organ systems. On the epidemiological and ecological fronts, limitations in reporting, ecological changes, and a lack of public support hinder accurate surveillance and enhance the spread of the disease. The goal of this literature review is to increase public knowledge of B. burgdorferi, its vector, and the disease it causes, along with suggesting preventative measures to protect individuals who reside in high-risk areas. A collective and coordinated public health effort represents our greatest chance of restraining the LD-causing pathogen.

The Neuroblastoma Microenvironment, Heterogeneity and Immunotherapeutic Approaches.

Neuroblastoma is a peripheral nervous system tumor that almost exclusively occurs in young children. Although intensified treatment modalities have led to increased patient survival, the prognosis for patients with high-risk disease is still around 50%, signifying neuroblastoma as a leading cause of cancer-related deaths in children. Neuroblastoma is an embryonal tumor and is shaped by its origin from cells within the neural crest. Hence, neuroblastoma usually presents with a low mutational burden and is, in the majority of cases, driven by epigenetically deregulated transcription networks. The recent development of Omic techniques has given us detailed knowledge of neuroblastoma evolution, heterogeneity, and plasticity, as well as intra- and intercellular molecular communication networks within the neuroblastoma microenvironment. Here, we discuss the potential of these recent discoveries with emphasis on new treatment modalities, including immunotherapies which hold promise for better future treatment regimens.

Fabrication of high-entropy alloy superconducting wires by powder-in-tube method

High-entropy alloys (HEAs) are novel functional materials that exhibit excellent mechanical and chemical properties. Recent discovery of self-healing superconductivity of HEAs under ion irradiation suggests their great potential applications under extreme conditions such as in nuclear fusion reactors or space environments. Here, we report a fabrication of the HEA superconducting (SC) wires using the ex-situ powder-in-tube (PIT) technique for the first time, a crucial stepping stone to achieve various industrial and technological applications. The Ta1/6Nb2/6Hf1/6Zr1/6Ti1/6 HEA SC powder prepared by planetary ball milling was filled into Fe tubes, drawn into wires, and then sintered in evacuated quartz tubes at various temperatures. The HEA SC wire sintered at 700 °C for 1 h exhibits the highest critical current density (Jc) among the HEA SC wires sintered in the temperature range of 600 – 1000 °C. At 4.2 K, the Jc of this wire exceeds the common benchmark value of Jc = 100 kA cm−2, indicating the suitability of the HEA wire for large-scale applications, such as in high-field SC magnets. The SC transition temperature (Tc) of the HEA wire significantly increases from 5.10 K for the as-cast wire to 7.58 K with the sintering time (ts) of 30 min at 700 °C. The scaling of the flux pinning force as a function of the magnetic field indicates that normal point pinning plays a major role in achieving a high in-field Jc in HEA SC wires. These results underscore the significant potential of HEA superconductors for practical applications in high-field SC magnets, SC electric machines, and next-generation nuclear fusion reactors.

Updates in the role of the tumor microenvironment cellular crosstalk and genetic signatures in diffuse large B-cell lymphoma: a narrative review.

The tumor microenvironment (TME) is known to exert a significant impact on disease biology and convey prognostic and therapeutic implications in several hematopoietic neoplasms, including diffuse large B-cell lymphoma (DLBCL). Recent discoveries have yielded new information regarding the genetic signatures of the TME. This study aims to review the updates on the cellular markers and genetics of various components of the TME in DLBCL influencing tumor behavior and patients' responses to treatment and discuss the novel treatment modalities available for the patients. We systematically reviewed the literature in Medline for DLBCL-related articles on gene expression studies of TME. Forty-seven articles were identified and included that were published between Apr 2006 and Apr 2023. We review the key components of the TME including the endothelial cells, myofibroblasts and mast cells, and discuss their biologic roles, with a particular focus on elements of their crosstalk relevant to DLBCL. We also review the genetic changes in lymphocytes and macrophages in TME of DLBCL. Increased understanding of emergent molecular alterations may hopefully allow improved prognostication and translational discoveries which will benefit patients with aggressive B-cell lymphomas. Combining cell of origin and TME as a risk stratification/prognostication system could provide more effective targeted therapeutic regiments. Identifying TME-targeted therapies will happen after providing the TME markers in the DLBCLs.

Unconventional magnetism mediated by spin-phonon-photon coupling

Magnetic order typically emerges due to the short-range exchange interaction between the constituent electronic spins. Recent discoveries have found a crucial role for spin-phonon coupling in various phenomena from optical ultrafast magnetization switching to dynamical control of the magnetic state. Here, we demonstrate theoretically the emergence of a biquadratic long-range interaction between spins mediated by their coupling to phonons hybridized with vacuum photons into polaritons. The resulting ordered state enabled by the exchange of virtual polaritons between spins is reminiscent of superconductivity mediated by the exchange of virtual phonons. The biquadratic nature of the spin-spin interaction promotes ordering without favoring ferro- or antiferromagnetism. It further makes the phase transition to magnetic order a first-order transition, unlike in conventional magnets. Consequently, a large magnetization develops abruptly on lowering the temperature which could enable magnetic memories admitting ultralow-power thermally-assisted writing while maintaining a high data stability. The role of photons in the phenomenon further enables an in-situ static control over the magnetism. These unique features make our predicted spin-spin interaction and magnetism highly unconventional paving the way for novel scientific and technological opportunities.

Beyond the Quantum Membrane Paradigm: A Philosophical Analysis of the Structure of Black Holes in Full QG

This paper presents a philosophical analysis of the structure of black holes, focusing on the event horizon and its fundamental status. While black holes have been at the centre of countless paradoxes arising from the attempt to merge quantum mechanics and general relativity, recent experimental discoveries have emphasised their importance as objects for the development of Quantum Gravity. In particular, the statistical mechanical underpinning of black hole thermodynamics has been a central research topic. The Quantum Membrane Paradigm, proposed by Wallace (Stud Hist Philos Sci Part B 66:103-117, 2019), posits a real membrane made of black hole microstates at the black hole horizon to provide a statistical mechanical understanding of black hole thermodynamics from an exterior observer’s point of view. However, we argue that the Quantum Membrane Paradigm is limited to low-energy Quantum Gravity and needs to be modified to avoid reference to geometric notions, such as the event horizon, which presumably do not make sense in the non-spatiotemporal context of full Quantum Gravity. Our proposal relies on the central dogma of black hole physics. It considers recent developments, such as replica wormholes and entanglement wedge reconstruction, to provide a new framework for understanding the nature of black hole horizons in full Quantum Gravity.

Sex chromosome turnover in hybridizing stickleback lineages

Abstract Recent discoveries of sex chromosome diversity across the tree of life have challenged the canonical model of conserved sex chromosome evolution and evoked new theories on labile sex chromosomes that maintain less differentiation and undergo frequent turnover. However, theories of labile sex chromosome evolution lack direct empirical support due to the paucity of case studies demonstrating ongoing sex chromosome turnover in nature. Two divergent lineages (viz. WL & EL) of nine-spined sticklebacks (Pungitius pungitius) with different sex chromosomes (linkage group [LG] 12 in the EL, unknown in the WL) hybridize in a natural secondary contact zone in the Baltic Sea, providing an opportunity to study ongoing turnover between coexisting sex chromosomes. In this study, we first identify an 80 kbp genomic region on LG3 as the sex-determining region (SDR) using whole-genome resequencing data of family crosses of a WL population. We then verify this region as the SDR in most other WL populations and demonstrate a potentially ongoing sex chromosome turnover in admixed marine populations where the evolutionarily younger and homomorphic LG3 sex chromosome replaces the older and heteromorphic LG12 sex chromosome. The results provide a rare glimpse of sex chromosome turnover in the wild and indicate the possible existence of additional yet undiscovered sex chromosome diversity in Pungitius sticklebacks.

From Scraps to Solutions: Harnessing the Potential of Vegetable and Fruit Waste in Pharmaceutical Formulations

Background:: Food waste is a major worldwide problem due to the increasing population and imbalances in supply chains. Waste from fruits and vegetables are a substantial proportion of the overall food waste generated, accounting for approximately 42% of the waste produced. Methane, a strong greenhouse gas with a significant potential for global warming, is produced when these waste products are typically dumped in landfills. Objectives:: The study's goal is to present a thorough overview of the most recent findings and developments in the use of vegetable and fruit waste for creating therapeutic formulations. Recognizing the opportunities and challenges in this developing area of study, as well as the promise that vegetable and fruit waste contains for the creation of environmentally friendly and economically advantageous pharmaceutical formulations. Methods:: A comprehensive review of existing literature on the utilization of vegetable and fruit waste in pharmaceutical formulations was conducted. The review included studies on the chemical composition and bioactive compounds present in various types of vegetable and fruit waste, their extraction methods, and their potential applications in pharmaceutical formulations. Additionally, current waste management practices and challenges associated with waste disposal were also analyzed. Conclusion:: The review highlights the significant potential of vegetable and fruit waste in the development of pharmaceutical formulations. Fruit and vegetable waste offer a wide range of bioactive compounds, such as antioxidants, antimicrobials, and antiinflammatory agents, which could be utilized in drug formulation. Moreover, this approach can promote environmental sustainability by reducing waste generation and enhancing waste utilization. Further research and development efforts should focus on optimizing extraction methods, evaluating the efficacy and safety of wastederived compounds, and addressing regulatory requirements for integrating vegetable and fruit waste into pharmaceutical products. Harnessing the potential of vegetable and fruit waste in pharmaceutical formulations can lead to sustainable advancements in the pharmaceutical industry while addressing environmental concerns.

Emerging role of immunogenic cell death in cancer immunotherapy.

Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged as a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to cancer immunotherapy is suboptimal, primarily attributed to low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents a form of regulated cell death (RCD) capable of enhancing tumor immunogenicity and activating tumor-specific innate and adaptive immune responses in immunocompetent hosts. Therefore, gaining a deeper understanding of ICD and its evolution is crucial for developing more effective cancer therapeutic strategies. This review focuses exclusively on both historical and recent discoveries related to ICD modes and their mechanistic insights, particularly within the context of cancer immunotherapy. Our recent findings are also highlighted, revealing a mode of ICD induction facilitated by atypical interferon (IFN)-stimulated genes (ISGs), including polo-like kinase 2 (PLK2), during hyperactive type I IFN signaling. The review concludes by discussing the therapeutic potential of ICD, with special attention to its relevance in both preclinical and clinical settings within the field of cancer immunotherapy.

Identification and Characterization of the Glutathione S-Transferase Gene Family in Blueberry (Vaccinium corymbosum) and Their Potential Roles in Anthocyanin Intracellular Transportation.

The glutathione S-transferases (GSTs, EC 2.5.1.18) constitute a versatile enzyme family with pivotal roles in plant stress responses and detoxification processes. Recent discoveries attributed the additional function of facilitating anthocyanin intracellular transportation in plants to GSTs. Our study identified 178 VcGST genes from 12 distinct subfamilies in the blueberry genome. An uneven distribution was observed among these genes across blueberry's chromosomes. Members within the same subfamily displayed homogeneity in gene structure and conserved protein motifs, whereas marked divergence was noted among subfamilies. Functional annotations revealed that VcGSTs were significantly enriched in several gene ontology and KEGG pathway categories. Promoter regions of VcGST genes predominantly contain light-responsive, MYB-binding, and stress-responsive elements. The majority of VcGST genes are subject to purifying selection, with whole-genome duplication or segmental duplication serving as key processes that drive the expansion of the VcGST gene family. Notably, during the ripening of the blueberry fruit, 100 VcGST genes were highly expressed, and the expression patterns of 24 of these genes demonstrated a strong correlation with the dynamic content of fruit anthocyanins. Further analysis identified VcGSTF8, VcGSTF20, and VcGSTF22 as prime candidates of VcGST genes involved in the anthocyanin intracellular transport. This study provides a reference for the exploration of anthocyanin intracellular transport mechanisms and paves the way for investigating the spectrum of GST functions in blueberries.

Is spontaneous vortex generation in superconducting 4Hb-TaS2 from vison-vortex nucleation with Z2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathbb{Z}_{2}$\\end{document} topological order?

We propose the superconducting van der Waals material 4Hb-TaS2 to realize the Z2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathbb{Z}_{2}$\\end{document} topological order and interpret the recent discovery of the spontaneous vortex generation in 4Hb-TaS2 as the vison-vortex nucleation. For the alternating stacking of metallic/superconducting and Mott insulating layers in 4Hb-TaS2, we expect the local moments in the Mott insulating 1T-TaS2 layer to form the Z2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathbb{Z}_{2}$\\end{document} topological order. The spontaneous vortex generation in 4Hb-TaS2 is interpreted from the transition or nucleation between the superconducting vortex and the Z2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathbb{Z}_{2}$\\end{document} vison in different phase regimes. Differing from the single vison-vortex nucleation in the original Senthil–Fisher’s cuprate proposal, we consider such nucleation process between the superconducting vortex lattice and the vison crystal. We further propose experiments to distinguish this proposal with the Z2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathbb{Z}_{2}$\\end{document} topological order from the chiral spin liquid scenarios.

Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis.

The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp3)-C(sp3) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.