Mechanochemical Synthesis of Boroxine-linked Covalent Organic Frameworks.

We report a rapid, room-temperature mechanochemical synthesis of 2- and 3-dimensional boroxine covalent organic frameworks (COFs), enabled by using trimethylboroxine as a dehydrating additive to overcome the hydrolytic sensitivity of boroxine-based COFs. The resulting COFs display high porosity and crystallinity, with COF-102 being the first example of a mechanochemically prepared 3D COF, exhibiting a surface area of ca. 2,500 m2 g-1. Mechanochemistry enabled a >20-fold reduction in solvent use and ~100-fold reduction in reaction time compared with solvothermal methods, providing target COFs quantitatively with no additional work-up besides vacuum drying. Real-time Raman spectroscopy permitted the first quantitative kinetic analysis of COF mechanosynthesis, while transferring the reaction design to Resonant Acoustic Mixing (RAM) enabled synthesis of multi-gram amounts of the target COFs (tested up to 10 g).

ADHD prescription patterns and medication adherence in children and adolescents during the COVID-19 pandemic in an urban academic setting.

BACKGROUND: COVID-19 impacted all students, especially those with attention deficit hyperactivity disorder (ADHD), putting them at risk for disruption to their medication regimen and school performance. Our study aimed to identify if ADHD medication regimens were disrupted through analyzing prescription refills and if telehealth management demonstrated a higher rate of adherence. METHODS: A total of 396 patients from the General Academic Pediatrics (GAP) clinic at Children's Hospital of The King's Daughters (CHKD) were included in the study. Patients were between the ages of 8-18 with a history of ADHD for three or more years that was medically managed with four or more prescription refills between January 2019 and May 2022. A retrospective chart review collected age, sex, race, refill schedule, appointment schedule, and number of telehealth appointments. Data analysis compared the variables and defined "pre-pandemic months" as January 2019 through March 2020 and "pandemic months" as April 2020 through June 2022. RESULTS: The total percentage of patients who had their ADHD medications during pre-pandemic months ranged from 40 to 66% versus 31-44% during pandemic months. Additionally, the total percentage of patients who had quarterly ADHD management appointments during pre-pandemic months ranged between 59 and 70% versus 33-50% during pandemic months. The number of months with ADHD prescription refills over the last three years was significantly higher among those who had both virtual and in-person visits than those who had just in-person visits, p < 0.001. Regarding race, Black patients had a lower number of medication refills compared to White patients when controlled for appointment type. They also had a lower number of total appointments, but there was not a significant difference in the number of virtual appointments. CONCLUSIONS: Since the start of the pandemic, ADHD patients have both refilled their prescriptions and returned to clinic less frequently. This data suggests a need to re-evaluate the ADHD symptoms of GAP patients periodically and return them to a more consistent medication regimen. Telehealth appointments are a potential solution to increase adherence. However, racial inequities found in this study need to be addressed.

L-cysteine ethylester reverses the adverse effects of morphine on breathing and arterial blood-gas chemistry while minimally affecting antinociception in unanesthetized rats.

L-cysteine ethylester (L-CYSee) is a membrane-permeable analogue of L-cysteine with a variety of pharmacological effects. The purpose of this study was to determine the effects of L-CYSee on morphine-induced changes in ventilation, arterial-blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient (i.e., a measure of the index of alveolar gas-exchange), antinociception and sedation in male Sprague Dawley rats. An injection of morphine (10 mg/kg, IV) produced adverse effects on breathing, including sustained decreases in minute ventilation. L-CYSee (500 µmol/kg, IV) given 15 min later immediately reversed the actions of morphine. Another injection of L-CYSee (500 µmol/kg, IV) after 15 min elicited more pronounced excitatory ventilatory responses. L-CYSee (250 or 500 µmol/kg, IV) elicited a rapid and prolonged reversal of the actions of morphine (10 mg/kg, IV) on ABG chemistry (pH, pCO2, pO2, sO2) and A-a gradient. L-serine ethylester (an oxygen atom replaces the sulfur; 500 µmol/kg, IV), was ineffective in all studies. L-CYSee (500 µmol/kg, IV) did not alter morphine (10 mg/kg, IV)-induced sedation, but slightly reduced the overall duration of morphine (5 or 10 mg/kg, IV)-induced analgesia. In summary, L-CYSee rapidly overcame the effects of morphine on breathing and alveolar gas-exchange, while not affecting morphine sedation or early-stage analgesia. The mechanisms by which L-CYSee modulates morphine depression of breathing are unknown, but appear to require thiol-dependent processes.

Electrochemical Vicinal C-H Difunctionalization of Saturated Azaheterocycles.

A method to functionalize two vicinal C-H bonds of saturated azaheterocycles is described. The procedure involves subjecting the substrate to a mixture of hydrochloric acid, acetic acid, and acetic anhydride in an undivided electrochemical cell at a constant current, resulting in stereoselective conversion to the corresponding α-acetoxy-ß-chloro derivative. The α-position can be readily substituted with a range of other groups, including alkyl, aryl, allyl, alkynyl, alkoxy, or azido functionalities. Furthermore, we demonstrate that the ß-chloro position can be engaged in Suzuki cross-coupling. This protocol thus enables the rapid diversification of simple five-, six-, and seven-membered saturated azaheterocycles at two adjacent positions.

Diazene-Catalyzed Oxidative Alkyl Halide-Olefin Metathesis.

The first platform for oxidative alkyl halide-olefin metathesis is described. The procedure employs diazenes as catalysts, which effect the cyclization of alkenyl alkyl halides to generate cyclic olefins and carbonyl products. The synthesis of phenanthrene, coumarin, and quinolone derivatives is demonstrated as well as the potential to apply this strategy to other electrophiles.

Three-in-One: Dye-Volatile Cocrystals Exhibiting Intensity-Dependent Photochromic, Photomechanical, and Photocarving Response.

Cocrystallization of a cis-azobenzene dye with volatile molecules, such as pyrazine and dioxane, leads to materials that exhibit at least three different light-intensity-dependent responses upon irradiation with low-power visible light. The halogen-bond-driven assembly of the dye cis-(p-iodoperfluorophenyl)azobenzene with volatile halogen bond acceptors produces cocrystals whose light-induced behavior varies significantly depending on the intensity of the light applied. Low-intensity (<1 mW·cm-2) light irradiation leads to a color change associated with low levels of cis → trans isomerization. Irradiation at higher intensities (150 mW·mm-2) produces photomechanical bending, caused by more extensive isomerization of the dye. At still higher irradiation intensities (2.25 W·mm-2) the cocrystals undergo cold photocarving; i.e., they can be cut and written on with micrometer precision using laser light without a major thermal effect. Real-time Raman spectroscopy shows that this novel photochemical behavior differs from what would be expected from thermal energy input alone. Overall, this work introduces a rational blueprint, based on supramolecular chemistry in the solid state, for new types of crystalline light-responsive materials, which not only respond to being exposed to light but also change their response based on the light intensity.

Halogen bonding with carbon: directional assembly of non-derivatised aromatic carbon systems into robust supramolecular ladder architectures.

Carbon, although the central element in organic chemistry, has been traditionally neglected as a target for directional supramolecular interactions. The design of supramolecular structures involving carbon-rich molecules, such as arene hydrocarbons, has been limited almost exclusively to non-directional π-stacking, or derivatisation with heteroatoms to introduce molecular assembly recognition sites. As a result, the predictable assembly of non-derivatised, carbon-only π-systems using directional non-covalent interactions remains an unsolved fundamental challenge of solid-state supramolecular chemistry. Here, we propose and validate a different paradigm for the reliable assembly of carbon-only aromatic systems into predictable supramolecular architectures: not through non-directional π-stacking, but via specific and directional halogen bonding. We present a systematic experimental, theoretical and database study of halogen bonds to carbon-only π-systems (C-I⋯πC bonds), focusing on the synthesis and structural analysis of cocrystals with diversely-sized and -shaped non-derivatised arenes, from one-ring (benzene) to 15-ring (dicoronylene) polycyclic atomatic hydrocarbons (PAHs), and fullerene C60, along with theoretical calculations and a systematic analysis of the Cambridge Structural Database. This study establishes C-I⋯πC bonds as directional interactions to arrange planar and curved carbon-only aromatic systems into predictable supramolecular motifs. In >90% of herein presented structures, the C-I⋯πC bonds to PAHs lead to a general ladder motif, in which the arenes act as the rungs and halogen bond donors as the rails, establishing a unique example of a supramolecular synthon based on carbon-only molecules. Besides fundamental importance in the solid-state and supramolecular chemistry of arenes, this synthon enables access to materials with exciting properties based on simple, non-derivatised aromatic systems, as seen from large red and blue shifts in solid-state luminescence and room-temperature phosphorescence upon cocrystallisation.

Hypoxia releases S-nitrosocysteine from carotid body glomus cells-relevance to expression of the hypoxic ventilatory response.

We have provided indirect pharmacological evidence that hypoxia may trigger release of the S-nitrosothiol, S-nitroso-L-cysteine (L-CSNO), from primary carotid body glomus cells (PGCs) of rats that then activates chemosensory afferents of the carotid sinus nerve to elicit the hypoxic ventilatory response (HVR). The objective of this study was to provide direct evidence, using our capacitive S-nitrosothiol sensor, that L-CSNO is stored and released from PGCs extracted from male Sprague Dawley rat carotid bodies, and thus further pharmacological evidence for the role of S-nitrosothiols in mediating the HVR. Key findings of this study were that 1) lysates of PGCs contained an S-nitrosothiol with physico-chemical properties similar to L-CSNO rather than S-nitroso-L-glutathione (L-GSNO), 2) exposure of PGCs to a hypoxic challenge caused a significant increase in S-nitrosothiol concentrations in the perfusate to levels approaching 100 fM via mechanisms that required extracellular Ca2+, 3) the dose-dependent increases in minute ventilation elicited by arterial injections of L-CSNO and L-GSNO were likely due to activation of small diameter unmyelinated C-fiber carotid body chemoafferents, 4) L-CSNO, but not L-GSNO, responses were markedly reduced in rats receiving continuous infusion (10 µmol/kg/min, IV) of both S-methyl-L-cysteine (L-SMC) and S-ethyl-L-cysteine (L-SEC), 5) ventilatory responses to hypoxic gas challenge (10% O2, 90% N2) were also due to the activation of small diameter unmyelinated C-fiber carotid body chemoafferents, and 6) the HVR was markedly diminished in rats receiving L-SMC plus L-SEC. This data provides evidence that rat PGCs synthesize an S-nitrosothiol with similar properties to L-CSNO that is released in an extracellular Ca2+-dependent manner by hypoxia.

Differential regulation of MAP2 by phosphorylation events in proline-rich versus C-terminal domains.

MAP2 is a critical cytoskeletal regulator in neurons. The phosphorylation of MAP2 (MAP2-P) is well known to regulate core functions of MAP2, including microtubule (MT)/actin binding and facilitation of tubulin polymerization. However, site-specific studies of MAP2-P function in regions outside of the MT-binding domain (MTBD) are lacking. We previously identified a set of MAP2 phosphopeptides which are differentially expressed and predominantly increased in the cortex of individuals with schizophrenia relative to nonpsychiatric comparison subjects. The phosphopeptides originated not from the MTBD, but from the flanking proline-rich and C-terminal domains of MAP2. We sought to understand the contribution of MAP2-P at these sites on MAP2 function. To this end, we isolated a series of phosphomimetic MAP2C constructs and subjected them to cell-free tubulin polymerization, MT-binding, actin-binding, and actin polymerization assays. A subset of MAP2-P events significantly impaired these functions, with the two domains displaying different patterns of MAP2 regulation: proline-rich domain mutants T293E and T300E impaired MT assembly and actin-binding affinity but did not affect MT-binding, while C-terminal domain mutants S426E and S439D impaired all three functions. S443D also impaired MT assembly with minimal effects on MT- or actin-binding. Using heterologous cells, we also found that S426E but not T293E had a lower capability for process formation than the wild-type protein. These findings demonstrate the functional utility of MAP2-P in the proline-rich and C-terminal domains and point to distinct, domain-dependent regulations of MAP2 function, which can go on to affect cellular morphology.

Infrared light elicits endothelium-dependent vasodilation in isolated occipital arteries of the rat via soluble guanylyl cyclase-dependent mechanisms.

The left and right occipital arteries provide blood supply to afferent cell bodies in the ipsilateral nodose and petrosal ganglia. This supply is free of an effective blood-ganglion barrier, so changes in occipital artery blood flow directly affect the access of circulating factors to the afferent cell bodies. The application of infrared (IR) light to modulate neural and other cell processes has yielded information about basic biological processes within tissues and is gaining traction as a potential therapy for a variety of disease processes. To address whether IR can directly modulate vascular function, we performed wire myography studies to determine the actions of IR on occipital arteries isolated from male Sprague-Dawley rats. Based on our previous research that functionally-important differences exist between occipital artery segments close to their origin at the external carotid artery (ECA) and those closer to the nodose ganglion, the occipital arteries were dissected into two segments, one closer to the ECA and the other closer to the nodose ganglion. Segments were constricted with 5-hydroxytryptamine to a level equal to 50% of the maximal response generated by the application of a high (80 mM) concentration of K+ ions. The direct application of pulsed IR (1,460 nm) for 5 s produced a rapid vasodilation in occipital arteries that was significantly more pronounced in segments closest to the ECA, although the ECA itself was minimally responsive. The vasodilation remained for a substantial time (at least 120 s) after cessation of IR application. The vasodilation during and following cessation of the IR application was markedly diminished in occipital arteries denuded of the endothelium. In addition, the vasodilation elicited by IR in endothelium-intact occipital arteries was substantially reduced in the presence of a selective inhibitor of the nitric oxide-sensitive guanylate cyclase, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ). It appears that IR causes endothelium-dependent, nitric-oxide-mediated vasodilation in the occipital arteries of the rat. The ability of IR to generate rapid and sustained vasodilation may provide new therapeutic approaches for restoring or improving blood flow to targeted tissues.

Direct mechanocatalysis by resonant acoustic mixing (RAM).

We demonstrate the use of a metal surface to directly catalyse copper-catalysed alkyne-azide click-coupling (CuAAC) reactions under the conditions of Resonant Acoustic Mixing (RAM) - a recently introduced and scalable mechanochemical methodology that uniquely eliminates the need for bulk solvent, as well as milling media. By using a simple copper coil as a catalyst, this work shows that direct mechanocatalysis can occur in an impact-free environment, relying solely on high-speed mixing of reagents against a metal surface, without the need for specially designed milling containers and media. By introducing an experimental setup that enables real-time Raman spectroscopy monitoring of RAM processes, we demonstrate 0th-order reaction kinetics for several selected CuAAC reactions, supporting surface-based catalysis. The herein presented RAM-based direct mechanocatalysis methodology is simple, enables the effective one-pot, two-step synthesis of triazoles via a combination of benzyl azide formation and CuAAC reactions on a wide scope of reagents, provides control over reaction stoichiometry that is herein shown to be superior to that seen in solution or by using more conventional CuCl catalyst, and is applied for simple gram-scale synthesis of the anticonvulsant drug Rufinamide.

Cross-Coupling of Amines via Photocatalytic Denitrogenation of In Situ Generated Diazenes.

A method for C(sp3)-C(sp3) cross-coupling of amines is described. Primary amines are converted to 1,2-dialkyldiazenes by treatment with O-nosylhydroxylamines in the presence of atmospheric oxygen. Denitrogenation of the diazenes with an iridium photocatalyst then forges the C-C bond. The substrate scope accommodates a broad latitude of functionality, including heteroaromatics and unprotected alcohols and acids.

Olefination of carbonyls with alkenes enabled by electrophotocatalytic generation of distonic radical cations.

The conversion of carbonyls to olefins is a transformation of great importance for complex molecule synthesis. Standard methods use stoichiometric reagents that have poor atom economy and require strongly basic conditions, which limit their functional group compatibility. An ideal solution would be to catalytically olefinate carbonyls under nonbasic conditions using simple and widely available alkenes, yet no such broadly applicable reaction is known. Here, we demonstrate a tandem electrochemical/electrophotocatalytic reaction to olefinate aldehydes and ketones with a broad range of unactivated alkenes. This method involves the oxidation-induced denitrogenation of cyclic diazenes to form 1,3-distonic radical cations that rearrange to yield the olefin products. This olefination reaction is enabled by an electrophotocatalyst that inhibits back-electron transfer to the radical cation intermediate, thus allowing for the selective formation of olefin products. The method is compatible with a wide range of aldehydes, ketones, and alkene partners.

Hypercapnic signaling influences hypoxic signaling in the control of breathing in C57BL6 mice.

Interactions between hypoxic and hypercapnic signaling pathways, expressed as ventilatory changes occurring during and following a simultaneous hypoxic-hypercapnic gas challenge (HH-C) have not been determined systematically in mice. This study in unanesthetized male C57BL6 mice addressed the hypothesis that hypoxic (HX) and hypercapnic (HC) signaling events display an array of interactions indicative of coordination by peripheral and central respiratory mechanisms. We evaluated the ventilatory responses elicited by hypoxic (HX-C, 10%, O2, 90% N2), hypercapnic (HC-C, 5% CO2, 21%, O2, 90% N2), and HH-C (10% O2, 5%, CO2, 85% N2) challenges to determine whether ventilatory responses elicited by HH-C were simply additive of responses elicited by HX-C and HC-C, or whether other patterns of interactions existed. Responses elicited by HH-C were additive for tidal volume, minute ventilation and expiratory time, among others. Responses elicited by HH-C were hypoadditive of the HX-C and HC-C responses (i.e., HH-C responses were less than expected by simple addition of HX-C and HC-C responses) for frequency of breathing, inspiratory time and relaxation time, among others. In addition, end-expiratory pause increased during HX-C, but decreased during HC-C and HH-C, therefore showing that HC-C responses influenced the HX-C responses when given simultaneously. Return to room-air responses was additive for tidal volume and minute ventilation, among others, whereas they were hypoadditive for frequency of breathing, inspiratory time, peak inspiratory flow, apneic pause, inspiratory and expiratory drives, and rejection index. These data show that HX-C and HH-C signaling pathways interact with one another in additive and often hypoadditive processes.NEW & NOTEWORTHY We present data showing that the ventilatory responses elicited by a hypoxic gas challenge in male C57BL6 mice are markedly altered by coexposure to hypercapnic gas challenge with hypercapnic responses often dominating the hypoxic responses. These data suggest that hypercapnic signaling processes activated within brainstem regions, such as the retrotrapezoid nuclei, may directly modulate the signaling processes within the nuclei tractus solitarius resulting from hypoxic-induced increase in carotid body chemoreceptor input to these nuclei.

Peripheral nerve injury elicits microstructural and neurochemical changes in the striatum and substantia nigra of a DYT-TOR1A mouse model with dystonia-like movements.

The relationship between genotype and phenotype in DYT-TOR1A dystonia as well as the associated motor circuit alterations are still insufficiently understood. DYT-TOR1A dystonia has a remarkably reduced penetrance of 20-30%, which has led to the second-hit hypothesis emphasizing an important role of extragenetic factors in the symptomatogenesis of TOR1A mutation carriers. To analyze whether recovery from a peripheral nerve injury can trigger a dystonic phenotype in asymptomatic hΔGAG3 mice, which overexpress human mutated torsinA, a sciatic nerve crush was applied. An observer-based scoring system as well as an unbiased deep-learning based characterization of the phenotype showed that recovery from a sciatic nerve crush leads to significantly more dystonia-like movements in hΔGAG3 animals compared to wildtype control animals, which persisted over the entire monitored period of 12 weeks. In the basal ganglia, the analysis of medium spiny neurons revealed a significantly reduced number of dendrites, dendrite length and number of spines in the naïve and nerve-crushed hΔGAG3 mice compared to both wildtype control groups indicative of an endophenotypical trait. The volume of striatal calretinin+ interneurons showed alterations in hΔGAG3 mice compared to the wt groups. Nerve-injury related changes were found for striatal ChAT+, parvalbumin+ and nNOS+ interneurons in both genotypes. The dopaminergic neurons of the substantia nigra remained unchanged in number across all groups, however, the cell volume was significantly increased in nerve-crushed hΔGAG3 mice compared to naïve hΔGAG3 mice and wildtype littermates. Moreover, in vivo microdialysis showed an increase of dopamine and its metabolites in the striatum comparing nerve-crushed hΔGAG3 mice to all other groups. The induction of a dystonia-like phenotype in genetically predisposed DYT-TOR1A mice highlights the importance of extragenetic factors in the symptomatogenesis of DYT-TOR1A dystonia. Our experimental approach allowed us to dissect microstructural and neurochemical abnormalities in the basal ganglia, which either reflected a genetic predisposition or endophenotype in DYT-TOR1A mice or a correlate of the induced dystonic phenotype. In particular, neurochemical and morphological changes of the nigrostriatal dopaminergic system were correlated with symptomatogenesis.

Single-Photon Source in a Topological Cavity.

The introduction of topological physics into the field of photonics has led to the development of photonic devices endowed with robustness against structural disorder. While a range of platforms have been successfully implemented demonstrating topological protection of light in the classical domain, the implementation of quantum light sources in photonic devices harnessing topologically nontrivial resonances is largely unexplored. Here, we demonstrate a single photon source based on a single semiconductor quantum dot coupled to a topologically nontrivial Su-Schrieffer-Heeger (SSH) cavity mode. We provide an in-depth study of Purcell enhancement for this topological quantum light source and demonstrate its emission of nonclassical light on demand. Our approach is a promising step toward the application of topological cavities in quantum photonics.

Electrophotocatalytic oxygenation of multiple adjacent C-H bonds.

Oxygen-containing functional groups are nearly ubiquitous in complex small molecules. The installation of multiple C-O bonds by the concurrent oxygenation of contiguous C-H bonds in a selective fashion would be highly desirable but has largely been the purview of biosynthesis. Multiple, concurrent C-H bond oxygenation reactions by synthetic means presents a challenge1-6, particularly because of the risk of overoxidation. Here we report the selective oxygenation of two or three contiguous C-H bonds by dehydrogenation and oxygenation, enabling the conversion of simple alkylarenes or trifluoroacetamides to their corresponding di- or triacetoxylates. The method achieves such transformations by the repeated operation of a potent oxidative catalyst, but under conditions that are sufficiently selective to avoid destructive overoxidation. These reactions are achieved using electrophotocatalysis7, a process that harnesses the energy of both light and electricity to promote chemical reactions. Notably, the judicious choice of acid allows for the selective synthesis of either di- or trioxygenated products.

The "η-sweet-spot" (ηmax) in liquid-assisted mechanochemistry: polymorph control and the role of a liquid additive as either a catalyst or an inhibitor in resonant acoustic mixing (RAM).

Resonant acoustic mixing (RAM) offers a simple, efficient route for mechanochemical synthesis in the absence of milling media or bulk solvents. Here, we show the use of RAM to conduct the copper-catalysed coupling of sulfonamides and carbodiimides. This coupling was previously reported to take place only by mechanochemical ball milling, while in conventional solution environments it is not efficient, or does not take place at all. The results demonstrate RAM as a suitable methodology to conduct reactions previously accessed only by ball milling and provide a detailed, systematic overview of how the amount of liquid additive, measured by the ratio of liquid volume to weight of reactants (η, in µL mg-1), can affect the course of a mechanochemical reaction and the polymorphic composition of its product. Switching from ball milling to RAM allowed for the discovery of a new polymorph of the model sulfonylguanidine obtained by catalytic coupling of di(cyclohexyl)carbodiimide (DCC) and p-toluenesulfonamide, and the ability to control reaction temperature in RAM enabled in situ control of the polymorphic behaviour of this nascent product. We show that the reaction conversion for a given reaction time does not change monotonically but, instead, achieves a maximum for a well-defined η-value. This "η-sweet-spot" of conversion is herein designated ηmax. The herein explored reactions demonstrate sensitivity to η on the order of 0.01 µL mg-1, which corresponds to an amount of liquid additive below 5 mol% compared to the reactants, and is at least one to two orders of magnitude lower than the η-value typically considered in the design of liquid-assisted ball milling mechanochemical reactions. Such sensitivity suggests that strategies to optimise liquid-assisted mechanochemical reactions should systematically evaluate η-values at increments of 0.01 µL mg-1, or even finer. At η-values other than ηmax the reaction conversion drops off, demonstrating that the same liquid additive can act either as a catalyst or an inhibitor of a mechanochemical reaction, depending on the amount.

Solid-State Enzymatic Hydrolysis of Mixed PET/Cotton Textiles.

Waste polyester textiles are not recycled due to separation challenges and partial structural degradation during use and recycling. Chemical recycling of polyethylene terephthalate (PET) textiles through depolymerization can provide a feedstock of recycled monomers to make "as-new" polymers. While enzymatic PET recycling is a more selective and more sustainable approach, methods in development, however, have thus far been limited to clean, high-quality PET feedstocks, and require an energy-intensive melt-amorphization step ahead of enzymatic treatment. Here, high-crystallinity PET in mixed PET/cotton textiles could be directly and selectively depolymerized to terephthalic acid (TPA) by using a commercial cutinase from Humicola insolens under moist-solid reaction conditions, affording up to 30±2 % yield of TPA. The process was readily combined with cotton depolymerization through simultaneous or sequential application of the cellulase enzymes CTec2®, providing up to 83±4 % yield of glucose without any negative influence on the TPA yield.