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Terpene synthesis stands at the forefront of modern synthetic chemistry and represents the state-of-the-art in the chemist’s toolbox. Notwithstanding, these endeavors are inherently tied to the current availability of natural cyclic building blocks. Addressing this limitation, the stereocontrolled cyclization of abundant unbiased linear terpenes emerges as a valuable tool, which is still difficult to achieve with chemical catalysts. In this study, we showcase the remarkable capabilities of squalene-hopene cyclases (SHCs) in the chemoenzymatic synthesis of head-to-tail-fused terpenes. By combining engineered SHCs and a practical reaction setup, we generate ten chiral scaffolds with >99% ee and de , at up to decagram scale. Our mechanistic insights suggest how cyclodextrin encapsulation of terpenes may influence the performance of the membrane-bound enzyme. Moreover, we transform the chiral templates to valuable (mero)-terpenes using interdisciplinary synthetic methods, including a catalytic ring-contraction of enol-ethers facilitated by cooperative iodine/lipase catalysis. Terpene synthesis is limited by the current availability of natural cyclic building blocks. In this study, the authors employ squalene-hopene cyclases in the chemoenzymatic synthesis of head-to-tail fused terpenes and generate ten chiral scaffolds with >99% ee and de, at up to decagram scale.

While formative and summative usability testing is essential to confirm safe and effective product use, it may not be sufficient to comprehensively understand user capabilities and limitations in device interactions. Therefore, this research aims to quantify user handling forces for different device handling steps of pen injectors through sensor-augmented simulated use studies. The study involved 46 participants who were divided into two groups: a healthy control group and a group of users with dexterity impairments. All participants were instructed to perform simulated handling steps using non-functional dummy devices equipped with force and torque sensors. Each handling step was performed twice: first at what participants considered a comfortable force level and then at their maximum force. The study then analyzed force data to investigate the impact of user characteristics and device geometry on force exertion during the different handling steps. The study demonstrates differences in the perceived comfortable and maximum force levels between the control and patient groups. These force levels decrease slightly with the user's age and level of dexterity impairment. Furthermore, the forces applied by the users are dependent on the geometry of the device and the holding pattern. The results highlight the significance of sensor-augmented simulated use studies as a tool for providing quantitative insights into users' ability to exert force while handling self-injection devices. These data offer comprehensive insights that inform the definition of performance requirements and specifications for injection device design, thereby supporting the advancement of future self-injection devices.

In this study, the mobility of nanoparticles in mucus and similar hydrogels as model systems was assessed to elucidate the link between microscopic diffusion behavior and macroscopic penetration of such gels. Differences in particle adhesion to mucus components were strongly dependent on particle coating. Particles coated with 2 kDa PEG exhibited a decreased adhesion to mucus components, whereas chitosan strongly increased the adhesion. Despite such mucoinert properties of PEG, magnetic nanoparticles of both coatings did not penetrate through native respiratory mucus, resisting high magnetic forces (even for several hours). However, model hydrogels were, indeed, penetrated by both particles in dependency of particle coating, obeying the theory of particle mobility in an external force field. Comparison of penetration data with cryogenic scanning EM images of mucus and the applied model systems suggested particularly high rigidity of the mucin scaffold and a broad pore size distribution in mucus as reasons for the observed particle immobilization. Active probing of the rigidity of mucus and model gels with optical tweezers was used in this context to confirm such properties of mucus on the microscale, thus presenting the missing link between micro- and macroscopical observations. Because of high heterogeneity in the size of the voids and pores in mucus, on small scales, particle mobility will depend on adhesive or inert properties. However, particle translocation over distances larger than a few micrometers is restricted by highly rigid structures within the mucus mesh.

Inorganic–organic hybrid polymers are promising alternatives to simple organic polymers. They combine the advantages of organic and inorganic components in one homogeneous material, which can be adjusted to match sophisticated demands for various possible applications ranging from soft silicones to hard hybrid ceramics. Typically, the inorganic network is formed by a sol-gel reaction whereas the organic network is built by a polymerization reaction. Due to their complex architecture on a molecular level, it is often impossible to experimentally obtain information on the atomistic structures of such hybrid materials. In this work, we validate the all-atom COMPASS force field for the simulation of such materials on the basis of a simplified test system with (methacryloyloxymethyl)dimethylethoxysilane as a precursor; which has only one functionality for inorganic condensation, building only one defined condensation product in the sol-gel reaction. The force field was validated based on the experimentally determined single crystal structure of this condensation product and the calculation of its glass transition and melting temperatures by molecular dynamics. The prediction of fluid densities was validated on liquids of the precursor and the condensation product. The validated force field is applied to demonstrate the influence of inorganic cross-linking in the resulting polymer on a simplified network model. Graphical Abstract

This research paper contributes to the literature of deterrence theory in general, and in particular, with respect to white-collar crime, offering valuable insight by using a unique dataset of fraud and violation of trust incidents within the jurisdiction of Paraguay. Descriptive evidence shows a clear and continuous misallocation of funds and human capital, therefore providing less efficient services for the public. Regression analysis suggests that clearance rate exerts a highly significant effect in deterring fraud, but the results are not clear for violation of trust incidents. Despite the limitations of available data, results confirm the deterrence theory in Paraguay. However, for more than two-thirds of victims, not even an attempt was made to seek justice. As a side-result, it seems that a soft-on-crime strategy, induced from the former German penal code, has led to an increasing share of pre-trial diversion, therefore enhancing white-collar crimes like fraud and violation of trust, due to impunity.

Background Per oral endoscopic myotomy (POEM) is increasingly utilized to treat patients with achalasia. Early results have demonstrated significant improvement of symptoms, but there are concerns about postoperative reflux. With only limited comparative data available, we sought to compare POEM to laparoscopic Heller myotomy (LHM) with partial fundoplication. Methods This is a retrospective review of 42 POEM and 84 LHM patients undergoing primary myotomy for achalasia. Patients were matched by achalasia type, by Eckardt and dysphagia scores, and by quality of life (QOL) metrics. Analysis at 6–12-month follow-up evaluated these metrics, PPI use, pH, manometric, and endoscopic data. Results We matched 25 patients with achalasia types I (6), II (13), and III (6). Follow-up was longer for LHM at 158.1 (36.5–272.9) weeks versus 36.2 (22.2–41.2) weeks ( p  = 0.001). Eckardt scores, QOL metrics, and dysphagia significantly improved in both groups. DeMeester scores and total percent time less than 4 were abnormal in both groups and comparable ( p  = 0.925 and p  = 0.838). Esophagitis was seen in 53.4 % (POEM) and 31.6 % (LHM) (Yates’ p  = 0.91), and PPI use was equivalent at 36 %. Conclusion Early clinical outcomes are excellent with POEM and comparable to the standard of care LHM. Long-term follow-up is required as concerns for reflux persist.

Squalene-hopene cyclases are a highly valuable and attractive class of membrane-bound enzymes as sustainable biotechnological tools to produce aromas and bioactive compounds at industrial scale. However, their application as whole-cell biocatalysts suffer from the outer cell membrane acting as a diffusion barrier for the highly hydrophobic substrate/product, while the use of purified enzymes leads to dramatic loss of stability. Here we present an unexplored strategy for biocatalysis: the application of squalene-hopene-cyclase spheroplasts. By removing the outer cell membrane, we produce stable and substrate-accessible biocatalysts. These spheroplasts exhibit up to 100-fold higher activity than their whole-cell counterparts for the biotransformations of squalene, geranyl acetone, farnesol, and farnesyl acetone. Their catalytic ability is also higher than the purified enzyme for all high molecular weight terpenes. In addition, we introduce a concept for the carrier-free immobilization of spheroplasts via crosslinking, crosslinked spheroplasts. The crosslinked spheroplasts maintain the same catalytic activity of the spheroplasts, offering additional advantages such as recycling and reuse. These timely solutions contribute not only to harness the catalytic potential of the squalene-hopene cyclases, but also to make biocatalytic processes even greener and more cost-efficient. Squalene-hopene cyclase are membrane-bound enzymes used to produce bioactive compounds at industrial scale. Here, the authors show squalene-hopene cyclase spheroplasts, obtained by removing the outer cell membrane, having a higher catalytic activity than the enzymes and the whole cells, and their cross-linking for recycling and reuse.

Background The rhizosphere is a critical microenvironment that plays key roles in plant nutrient availability, largely due to root interactions with rhizospheric microbes. However, we lack suitable methods that can elucidate mechanisms determining rhizospheric community structure and function within the context of a dynamic, undisturbed soil. Microdialysis has been used for low intrusive soil nutrient sampling at the scale of a fine root, with small probes that also enable release of defined compounds. We evaluated whether microdialysis could simulate exudation, by the release of sucrose, and stimulate changes in a soil microbial community, allowing us to determine the microbes that responded most to carbon release. Results Microdialysis successfully stimulated growth on probe surfaces of fungi and bacteria, which were extracted and sequenced for identification. Microbial growth was also visualized with scanning electron microscopy. The majority of the species stimulated were classified as fast growing or opportunistic, e.g. yeasts, moulds, proteobacteria and actinobacteriota, which are known to respond quickly (within days) to the release of simple sugars as exudates in the rhizosphere. Conclusions The study demonstrates the potential of using microdialysis as a tool to investigate interactions between root exudation and soil microbial community composition, initially for individual compounds and in the future for more complex compositions.

Carbon storage and cycling in boreal forests—the largest terrestrial carbon store—is moderated by complex interactions between trees and soil microorganisms. However, existing methods limit our ability to predict how changes in environmental conditions will alter these associations and the essential ecosystem services they provide. To address this, we developed a metatranscriptomic approach to analyze the impact of nutrient enrichment on Norway spruce fine roots and the community structure, function, and tree–microbe coordination of over 350 root-associated fungal species. In response to altered nutrient status, host trees redefined their relationship with the fungal community by reducing sugar efflux carriers and enhancing defense processes. This resulted in a profound restructuring of the fungal community and a collapse in functional coordination between the tree and the dominant Basidiomycete species, and an increase in functional coordination with versatile Ascomycete species. As such, there was a functional shift in community dominance from Basidiomycetes species, with important roles in enzymatically cycling recalcitrant carbon, to Ascomycete species that have melanized cell walls that are highly resistant to degradation. These changes were accompanied by prominent shifts in transcriptional coordination between over 60 predicted fungal effectors, with more than 5,000 Norway spruce transcripts, providing mechanistic insight into the complex molecular dialogue coordinating host trees and their fungal partners. The host–microbe dynamics captured by this study functionally inform how these complex and sensitive biological relationships may mediate the carbon storage potential of boreal soils under changing nutrient conditions.

Since the late 2000s, the availability of high-quality cadmium zinc telluride (CdZnTe) has greatly increased. The excellent spectroscopic performance of this material has enabled the development of detectors with volumes exceeding 1 cm3 for use in the detection of nuclear materials. CdZnTe is also of great interest to the photon science community for applications in X-ray imaging cameras at synchrotron light sources and free electron lasers. Historically, spatial variations in the crystal properties and temporal instabilities under high-intensity irradiation has limited the use of CdZnTe detectors in these applications. Recently, Redlen Technologies have developed high-flux-capable CdZnTe material (HF-CdZnTe), which promises improved spatial and temporal stability. In this paper, the results of the characterization of 10 HF-CdZnTe detectors with dimensions of 20.35 mm × 20.45 mm × 2.00 mm are presented. Each sensor has 80 × 80 pixels on a 250-μm pitch and were flip-chip-bonded to the STFC HEXITEC ASIC. These devices show excellent spectroscopic performance at room temperature, with an average Full Width at Half Maximum (FWHM) of 0.83 keV measured at 59.54 keV. The effect of tellurium inclusions in these devices was found to be negligible; however, some detectors did show significant concentrations of scratches and dislocation walls. An investigation of the detector stability over 12 h of continuous operation showed negligible changes in performance.