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This article describes a program that was developed to introduce senior high school students in Melbourne, Australia to the technique of X-ray crystallography within the context of chemistry research. Students had an opportunity for original experimentation, performing reactions and attempting to grow crystals of reaction products in a school laboratory. The program was remarkably successful, based on student feedback and scientific outcomes. In most cases, the compounds generated by students had not been synthesized before and their structures were previously unknown. X-ray diffraction data were collected on these crystalline products, and the students participated in data analysis and structure determination. New crystal structures were submitted to the international Cambridge Structural Database, with appropriate recognition of the students involved. Two peer-reviewed reports have been accepted for publication in the research literature with the students listed as coauthors. The experiences of the authors in developing this program should be of particular interest to science educators designing outreach activities for high school students.

This study adds to the growing body of research on laboratory work. The study involves four pairs of students in a university introductory calorimetry lab of which two pairs, the IR-pairs (infrared camerapairs), were given access to infrared cameras to use however they liked during their course lab work. Two other pairs, the T-pairs (thermometer-pairs), were not given access to infrared cameras during their course lab work. The IR-pairs were video recorded when they chose to use the IR cameras and the T-pairs were video-recorded during the corresponding sequences. Additionally, all pairs participated in a modified lab after their course lab, in which the pairs had access to IR cameras and were presented with the same phenomena although with equipment modified to better accommodate for the use of IR cameras (thin plastic cups were used instead of calorimeters). Students' practice, communication and reasoning was studied to explore how the IR cameras affect students' activity. The results show that the access to IR cameras led to a reasoning focused on a macroscopic level of chemistry knowledge, involving heat transfer to the surrounding and measurement errors, and that the lab practice of most of the students was continuous (rather than intermittent) when they had access to IR cameras. We conclude by arguing that the access to IR cameras affects students' conceptual and epistemological framing of the lab, i.e. that the students perceive the lab activity differently when they get access to IR cameras (both in a conceptual and epistemological sense). As an implication for teaching, we suggest that giving students access to IR cameras in a chemistry lab may be a way to introduce flexibility in the degree of openness of the lab.

To develop expertise, novice chemistry students require deliberate practice with immediate and thoughtful feedback. Whereas opportunities for practice are often abundant, opportunities for feedback tend to be much scarcer. To address this challenge, we collaborated with students to develop a flexible and scalable online platform called "Alchemy." Students interact with the software through a series of prompts and multiple-choice questions, receiving targeted feedback at each step. Each student can navigate a scenario differently, influenced by their prior knowledge and misconceptions. In design, scenarios are instructor-created graphs that model their expert-level thought process­(es) and teaching experience. This graph format is a distinct and advantageous feature of Alchemy that supports linear, nonlinear, and cyclical progression through a concept or problem. Alchemy-based homework has been assigned in lecture and lab courses, at the sophomore and junior levels, with enrollments ranging from many tens to many hundreds of students. Approximately 80% of students rated Alchemy as very/extremely helpful to their learning, emphasizing the value of the step-by-step process and feedback. Alchemy is discussed in the contexts of other software platforms, its advantages and limitations, lessons learned in its initial deployments, and future directions for its development and usage.

Lab activities typically involve phenomena that are invisible to the naked eye. For example, in thermodynamics transfer of heat and temperature changes are perceived by the sense of touch or indirectly observed by the use of thermometers. New tools can be introduced to increase the opportunities for talking science. In this paper, we explore affordances and semiotic resources related to infrared (IR) cameras, including color imaging, numerical values and the form of the tool itself, as used by undergraduate students and instructors in chemistry, representing a scientific community at two different levels of expertise, in investigation of a thermal phenomenon. The participants come to attend to thermal aspects of what happens when a salt (sodium hydroxide) is exposed to air, with and without the use of IR cameras. Video data were gathered and transcribed multimodally. Results show that the IR cameras afford a focus on the disciplinarily relevant thermal aspects of the phenomenon in both groups of participants, but that the students' discussion, coordinated by their embodied engagement with the IR cameras, was limited to cumulative talk, where they do not challenge each other, and static use of the technology. This is contrasted with the instructors who shared their knowledge with each other and explored the phenomenon both spatially with the IR cameras, and verbally through exploratory talk. We suggest that this difference in the use of novel technology may be due to differences in experience of lab work and understanding of the studied phenomena, and that a shift between cumulative and exploratory talk may be an indicator of learning.

The implementation of an integrated approach to upper-level undergraduate chemistry laboratory instruction that incorporates student choice both in the selection and sequencing of the experimental work is presented. The approach involves combining laboratory work in several traditional subdisciplinary areas of chemistry in a single course. Experimental work in emerging areas of chemistry is also incorporated, as are experiences intended to capture an interdisciplinary approach. Logistical affordances, the nature of the resulting learning environment, student responses, and faculty experiences are explored through analysis of curriculum documents and the use of student surveys. The work reveals several strengths and weaknesses in terms of logistics and learning environment, insights into how students engaged with the course and the aspect of choice, and associated benefits and challenges for faculty members. Implications for practice are presented with the aim of informing educators and institutions considering or adopting a similar approach.

A laboratory experiment introducing the concept of chemical bioconjugation of proteins to undergraduate students in a therapeutically relevant context was developed. Initially, students installed an aldehyde functionality into a protein via the oxidation of the N-terminal threonine residue of the cholera toxin subunit B (CTB) protein, which was followed by subsequent modification via hydrazone addition under mild conditions with a chromophore bearing a distinct UV-visabsorption peak. Students determined the yield of the reaction to be ca. 11% by HPLC coupled to UV-vis spectroscopy and developed key skills such as preparation of stock solutions, chemical manipulation of proteins, and analysis via HPLC. The reported experiment can be readily adapted for use with other proteins and may contribute to enhancing constructive alignment in interdisciplinary degree programs at the chemistry-biology interface.

In the United States with the Next Generation Science Standards (NGSS)'s emphasis on learning science while doing science, laboratory activities in the secondary school chemistry continues to be an important component of a strong curriculum. Laboratory equipment and consumable materials create a unique expense which chemistry teachers and schools must deal with if laboratory activities are part of the chemistry curriculum. While other barriers impacting teachers' use of laboratory activities have been researched, the impact of expense on teachers' choices is not as clear. This study sought to understand secondary school chemistry teachers' current laboratory practices and the impact expense has on their use of laboratory activities in their classroom. Using an online survey and follow-up interviews, the study found that a majority of secondary chemistry teachers surveyed use laboratory activities, though not always including scientific practices advocated by NGSS. The frequency of laboratory activities used by teachers was not statistically impacted by school type, available funds for materials, or processes to obtain funds, but was impacted by teachers' personal ideas. Interviews provided more information about the teachers using laboratory activities regularly and those not. While most teachers are using laboratory activities regularly at the current funding levels, expense, in terms of monetary and time expenses, was shown to impact the specific choice of laboratory activity. Implications for chemistry curriculum reform including the usage of laboratory activities in chemistry courses are discussed along with implications for chemistry teacher professional development.

It is not uncommon for students to view laboratory instruments as black boxes. Unfortunately, this can often result in poor experimental results and interpretation. To tackle this issue, a laboratory course was designed to enable students not only to critically think about operating principles of the instrument but also to improve interpretation skills. Students were required to build their own visible spectrometer using interlocking building bricks with simple optical elements and a Raspberry Pi computer. Experiments were then conducted to explore the instrumental capabilities while, at the same time, using Python programming to plot data, perform linear least-squares fitting, and calculate errors. Instrument response and spectral measurements were followed by kinetic studies, enabling the students to tackle a "real" problem by extracting rate constants. The main learning outcomes were that the students would gain a better understanding of instrumental components and at the same time learn valuable analytical techniques such as calibration, determination of the limits of linearity, and dynamic range. These outcomes were achieved by applying a problem based learning approach.

Abstract Controlling many-body interactions in two-dimensional systems remains a formidable task from the perspective of both fundamental physics and application. Here, we explore remarkable electronic structure alterations of MoS2 monolayer islands on graphene on Ir(111) induced by non-invasive self-intercalation. This introduces significant differences in morphology and strain of MoS2 as a result of the modified interaction with the substrate. Consequently, considerable changes of the band gap and non-rigid electronic shifts of valleys are detected, which are a combined effect of the screening of the many-body interactions and strain in MoS2. Furthermore, theory shows that each substrate leaves a unique stamp on the electronic structure of two-dimensional material in terms of those two parameters, restricted by their correlation.

Although vacuum technology is essential to many aspects of modern physical and analytical chemistry, vacuum experiments are rarely the focus of undergraduate laboratories. We describe an experiment that introduces students to vacuum science and mass spectrometry. The students first assemble a vacuum system, including a mass spectrometer. While assembling the vacuum system students learn about the components and the conditions necessary to operate a mass spectrometer. Then students use their assembled system to explore mass spectrometry; they use the mass spectrometer to diagnose vacuum conditions, then collect the mass spectrum of an unknown organic molecule, and propose the identity of the molecule.

Portions of classic undergraduate quantitative analysis experiments in complexiometric titration and potentiometry are combined with a field-sampling experience to create a two period (2 × 3 h) comparison-based experiment for second-year students. A multifunctional chemical analysis device is used with calcium ion-selective electrode for field measurement of calcium concentration in seawater. The results are compared with later simultaneous potentiometric and colorimetric titration with ethylenediaminetetraacetic acid (EDTA). Students compare precision, difficulty, and sources of error of the different methods and present a written argument supporting their choice of best method including advantages and limitations. The experiment provides an introduction to chemistry in-the-field, sample collection and handling, complex matrices, imperfect methods, fallibility of instrumentation, real-world performance, and decision-making.

This experiment describes the synthesis and characterization of a formazan dye, and its subsequent conversion to a stable verdazyl radical and a boron-nitrogen heterocycle (boratatetrazine). Each of these compounds is intensely colored and is prepared and handled under aerobic conditions, which often surprises students as free radicals are generally described as short-lived, highly reactive species and compounds containing boron are often assumed to be air-sensitive. The prepared compounds are studied by [superscript 1]H and [superscript 13]C NMR, UV-vis, and EPR spectroscopy. The UV-vis spectra introduce an opportunity to discuss the different energy transitions that may give rise to intense colors, and interpretation of the EPR spectrum requires the student to carefully consider the bonding within the verdazyl radical; that is, is the radical centered on one atom or is it shared over several atoms within the structure? In addition the crystal structures of the formazan and the boratatetrazine are viewed in detail, expanding the students' knowledge of bonding in delocalized systems. (Contains 3 figures and 3 schemes.)

A learning object is an interactive web-based tool that supports learning by enhancing, amplifying, and guiding the cognitive processes of a learner. To date, no formal research has been done on the use of learning objects in secondary school science classrooms. The purpose of this study was to evaluate the use of learning objects developed for high school students in areas of biology, chemistry, or physics. The evaluation metric used to assess the benefits and quality of learning objects was theoretically sound, reliable, and partially validated. Two thirds of the students stated they benefited from using the learning object. Teachers confirmed that learning objects were beneficial to student learning and that they would use them again. Students benefited more if they were comfortable with computers, the content was perceived as being useful, instructions were clear, and the theme was fun or motivating. Students appreciated the motivating, hands-on, and visual qualities of the learning objects most. Computer comfort and learning object type, but not gender, were significantly related to learning object quality and benefit. (Contains 4 tables.) [Appended to this document are: "Appendix A. Learning Object Survey for Students," and "Appendix B. Learning Object Survey for Teachers."]

Empirical research evaluating the effectiveness of learning objects is noticeably absent. No formal research has been done on the use of learning objects in secondary schools. The purpose of this study was to evaluate the use of learning objects by high school students. The evaluation metric used to assess benefits and quality of learning objects was theoretically sound, reliable, and partially validated. Overall, two-thirds of the students stated they benefitted from using learning objects. Students benefitted more if they were comfortable with computers, the learning object had a well organized layout, the instructions were clear, and the theme was fun or motivating. Students appreciated the motivational, interactive, visual qualities of the learning objects most. Computer comfort was significantly correlated with learning object quality and benefit. Younger students appeared to have less positive experiences than their older counterparts. There were no gender differences in perceived benefit or quality of learning objects, with one exception. Females emphasized the quality of help features significantly more than males. (Contains 11 tables.)

Roundhouse is a visually creative information-processing tool (J. E. Trowbridge and J. H. Wandersee 1998). The procedure requires learners to construct knowledge using "mindful" connections to replace less effective practices of memorizing fragmented information. Students create observable organization schemes of related ideas and icons in a logical sequence.

Abstract Human gamma-D crystallin (HGD) is a major constituent of the eye lens. Aggregation of HGD contributes to cataract formation, the leading cause of blindness worldwide. It is unique in its longevity, maintaining its folded and soluble state for 50-60 years. One outstanding question is the structural basis of this longevity despite oxidative aging and environmental stressors including ultraviolet radiation (UV). Here we present crystallographic structures evidencing a UV-induced crystallin redox switch mechanism. The room-temperature serial synchrotron crystallographic (SSX) structure of freshly prepared crystallin mutant (R36S) shows no post-translational modifications. After aging for nine months in the absence of light, a thiol-adduct (dithiothreitol) modifying surface cysteines is observed by low-dose SSX. This is shown to be UV-labile in an acutely light-exposed structure. This suggests a mechanism by which a major source of crystallin damage, UV, may also act as a rescuing factor in a finely balanced redox system.

A longitudinal study of students (n=250) following the Salters Advanced Chemistry course probed a range of chemical ideas including the exothermicity of bond formation and the development of thinking about covalent, ionic, and intermolecular bonds. At the start, many students demonstrated misunderstandings about these chemical ideas, but their understanding improved in general as the course progressed. (Author/SAH)

Explores changes in students' (n=250) thinking about basic chemical ideas during a context-based curricular approach. Suggests that 16- to 18-year-old students enter chemistry courses with a wide range of misunderstandings about chemical reactions, but understanding improves steadily as the course progresses. Concludes that even misunderstandings not addressed specifically in the course diminished among students further along in the program. Contains 29 references. (Author/WRM)

Terephthalic acid (H2TPA) solubility in several ionic liquids (ILs) at multiple concentrations is higher than for any other known solvents at lower temperatures and pressures which suggests low energy purification of H2TPA from its major impurity, 4-carboxybenzaldehyde (4-CBA) might be possible. To understand the mechanism several strategies were explored to purify H2TPA by taking advantage of this high solubilizing power of ILs for H2TPA in the crystallization of unique salts and cocrystals. Using either zwitterionic carboxylate IL-precursors or direct salt formation with carboxylate ILs or amines, a series of salts of mono, dibasic and two ionic cocrystals were obtained including monobasic, [C1C1im][HTPA], [N4441][HTPA], [C4C1im][HTPA]•0.5H2TPA (a cocrystal), and [C1Him][HTPA] ([C1C1im]+ = 1,3-dimethylimidazolium, [N4441]+ = tribuytlmethylammonium, [C1Him]+ = 1-methyl-3-H-imidazolium), dibasic [C1C1im]2[TPA], [C4C1im]2[TPA], [N4444]2[TPA], [C1Him]2[TPA], [H2N22]2[TPA], [H3N6]2[TPA], and [HN(CH2CH2OH)3]2[TPA] ([C4C1im]+ = 1-butyl-3-methylimidazolium, [N4444]+ = tetrabuylammonium, [H3N6]+ = hexylammonium, [HN(CH2CH2OH)3]+ = triethanolammonium, [H2N22]+= diethylammonium), and a second cocrystal [C2C1im]Cl•0.5H2TPA. The formation of these salts suggest a viable method to purify H2TPA because of preferred salt formation at low energy conditions. One elegant route using 1-ethyl-3-methylimidazolium chloride ([C2C1im]Cl) could be especially promising because the cocrystal [C2C1im]Cl•0.5H2TPA was readily isolated and is easily dissociated when exposed to ambient conditions into crystalline H2TPA and a liquid of hydrated [C2C1im]Cl.

In the past, sustainability or design for the environment was almost always considered at the end of the design process. This is no longer the case; sustainability is no longer [...]

Simple process energy measurement and analysis quickly and easily shows that machine selection and operation can dramatically affect energy use and profitability of injection molding. Barrel heating efficiency can be [...]

Describes the Mathematical and Scientific Foundations of Engineering curriculum which emphasizes the mathematical and scientific concepts common to all engineering fields. Scientists and engineers together devised topics and experiments that emphasize the relevance of theory to real-world applications. Presents material efficiently while building on the synergy of components. Summarizes class topics and contains 27 references. (PVD)

Abstract The electrochemical conversion of biobased intermediates offers an attractive and sustainable process for the production of green chemicals. One promising synthesis route is the production of the total vanillin-based polymer polyvanillin, which can be produced by electrochemical pinacolization of divanillin (5–5´bisvanillyl). Divanillin can be easily enzymatically generated from vanillin, a renewable intermediate accessible from lignin on an industrial scale. This study investigates systematically the electrochemical production of polyvanillin in a divided plane parallel flow reactor in recirculation mode. Several analytic methods, such as online UV–VIS spectroscopy, size exclusion chromatography (SEC), 2D-NMR (HSQC, 13C/1H), TGA and DSC were used to monitor the reaction progress and to characterize the reaction products under different galvanostatic reaction conditions revealing new insights into the reaction mechanism and structural features of the polymer. Further, by using an electrochemical engineering-based approach determining the limiting current densities, we readily achieved high current densities over 50 mA cm−2 for the polyvanillin synthesis and reached averaged molecular weights up to Mw = 4100 g mol−1 and Mn = 2700 g mol−1. The cathodic polymerization to polyvanillin offers an innovative approach for the electrochemical production of biobased polymers presented on flow cell level. Graphical Abstract

Dense urban environments pose significant challenges when it comes to detecting and measuring crowd size due to their nature of being free-flow environments containing many dynamic factors. In this paper, we use a wireless sensor network (WSN) to perform device-free crowd size estimation in a subway station. Our sensing solution uses the change in attenuation of the communication links between sensor nodes to estimate the number of people standing on the platform. In order to achieve this, we use the same attenuation information coming from the WSN to detect the presence of a rail vehicle in the station and compensate for the channel fading caused by the introduced rail vehicle. We make use of two separately trained regression models depending on the presence or absence of a rail vehicle to estimate the people count. The detection of rail vehicles occurred with a near-perfect accuracy. When evaluating the resulting estimation model on our test set, we achieved a mean average error of 3.567 people, which is a significant improvement over 6.192 people when using a single regression model. This demonstrates that device-free sensing technologies can be successfully implemented in dynamic environments by implementing detection techniques and using different regression models depending on the environment’s state.

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels’ adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects.

Understanding the niche interactions between blood and bone through the in vitro co-culture of osteo-competent cells and endothelial cells is a key factor in unraveling therapeutic potentials in bone regeneration. This can be additionally supported by employing numerical simulation techniques to assess local physical factors, such as oxygen concentration, and mechanical stimuli, such as shear stress, that can mediate cellular communication. In this study, we developed a Mesenchymal Stem Cell line (MSC) and a Human Umbilical Vein Endothelial Cell line (HUVEC), which were co-cultured under flow conditions in a three-dimensional, porous, natural pullulan/dextran scaffold that was supplemented with hydroxyapatite crystals that allowed for the spontaneous formation of spheroids. After 2 weeks, their viability was higher under the dynamic conditions (>94%) than the static conditions (

Chalcones constitute an important group of natural compounds abundant in fruits and comestible plants. They are a subject of increasing interest because of their biological activities, including anti-diabetic and anti-obesity effects. The simple chalcone structural scaffold can be modified at multiple sites with different chemical moieties. Here, we generated an artificial chalcone, i.e., 3,5-dimethyl-2,4,6-trimethoxychalcone (TriMetChalc), derived from 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC). DMC is a major compound of Cleistocalyx operculatus, a plant widely used in Asia for its anti-hyperglycemic activity. Using ob/ob mice as an obesity model, we report that, after 3 weeks of per os administration, TriMetChalc modified food intake through the specific activation of brain structures dedicated to the regulation of energy balance. TriMetChalc also decreased weight gain, glucose intolerance, and hepatic steatosis. Moreover, through extensive liver lipidomic analysis, we identified TriMetChalc-induced modifications that could contribute to improving the liver status of the animals. Hence, TriMetChalc is a chalcone derivative capable of reducing food intake and the addition of glucose intolerance and hepatic steatosis in a mouse model of obesity. In light of these results, we believe that TriMetChalc action deserves to be more deeply evaluated over longer treatment periods and/or in combination with other chalcones with protective effects on the liver.

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering.

Phenoxy radical coupling reactions are widely used in nature for the synthesis of complex molecules such as lignin. Their use in the laboratory has great potential for the production of high value compounds from the polyphenol family. While the enzymes responsible for the generation of the radicals are well known, the behavior of the latter is still enigmatic and difficult to control in a reaction flask. Previous work in our laboratory using the enzymatic secretome of B. cinerea containing laccases has shown that incubation of stilbenes leads to dimers, while incubation of phenylpropanoids leads to dimers as well as larger coupling products. Building on these previous studies, this paper investigates the role of different structural features in phenoxy radical couplings. We first demonstrate that the presence of an exocyclic conjugated double bond plays a role in the generation of efficient reactions. In addition, we show that the formation of phenylpropanoid trimers and tetramers can proceed via a decarboxylation reaction that regenerates this reactive moiety. Lastly, this study investigates the reactivity of other phenolic compounds: stilbene dimers, a dihydro-stilbene, a 4-O-methyl-stilbene and a simple phenol with the enzymatic secretome of B. cinerea. The observed efficient dimerization reactions consistently correlate with the presence of a para-phenol conjugated to an exocyclic double bond. The absence of this structural feature leads to variable results, with some compounds showing low conversion or no reaction at all. This research has allowed the development of a controlled method for the synthesis of specific dimers and tetramers of phenylpropanoid derivatives and novel stilbene derivatives, as well as an understanding of features that can promote efficient radical coupling reactions.

Abstract We present a luminescent Ir(III) complex featuring a bidentate halogen bond donor site capable of strong anion binding. The tailor‐made Ir(III)(L)2 moiety offers a significantly higher emission quantum yield (8.4 %) compared to previous Ir(III)‐based chemo‐sensors (2.5 %). The successful binding of chloride, bromide and acetate is demonstrated using emission titrations. These experiments reveal association constants of up to 1.6×105 M−1. Furthermore, a new approach to evaluate the association constant by utilizing the shift of the emission was used for the first time. The experimentally observed characteristics are supported by quantum chemical simulations.

Imidazole-4-carhoxamide (ICA), which is one of the groups of 'fairy chemicals' (FCs) that cause the fairy ring phenomena, has plant growth inhibitory activity. FCs have the potential as candidates for a new family of plant hormones as they have been found endogenously in all plant species tested and show growth-regulating activities against the plants. While basic research on FCs is progressing, they are also expected to be applied not only to agrochemicals but also as pharmaceuticals. Derivatization of one of the FCs, 2-azahypoxanthine, and the structure-activity relationship (SAR) studies have clarified its activity as a plant growth promoter. Yet, ICA has not been derivatized at all and SAR regarding its activity remains unknown. In this study we synthesized the derivatives of ICA by direct C--H arylation of ICA precursors and evaluated its activity in rice. The 12 total compounds including the arylated ICAs and their precursors were evaluated for root and shoot elongation in rice, resulting in the discovery that a number of compounds unexpectedly have an elongation activity in the root and shoot. Key words: C--H arylation, fairy chemicals, plant growth activity, imidazole-4-carboxamide, 'Fairy rings' is a phenomenon in which ring-shaped thick growths or necrotic spots of grasses occur. Since the first publication of a scientific paper on fairy rings in 1675, (1) [...]

Abstract Generative models are frequently used for de novo design in drug discovery projects to propose new molecules. However, the question of whether or not the generated molecules can be synthesized is not systematically taken into account during generation, even though being able to synthesize the generated molecules is a fundamental requirement for such methods to be useful in practice. Methods have been developed to estimate molecule “synthesizability”, but, so far, there is no consensus on whether or not a molecule is synthesizable. In this paper we introduce the Retro-Score (RScore), which computes a synthetic accessibility score of molecules by performing a full retrosynthetic analysis through our data-driven synthetic planning software Spaya, and its dedicated API: Spaya-API (https://spaya.ai). We start by comparing several synthetic accessibility scores to a binary “chemist score” as estimated by chemists on a bench of generated molecules, as a first experimental validation that the RScore is a reliable synthetic accessibility score. We then describe a pipeline to generate molecules that validate a list of targets while still being easy to synthesize. We further this idea by performing experiments comparing molecular generator outputs across a range of constraints and conditions. We show that the RScore can be learned by a Neural Network, which leads to a new score: RSPred. We demonstrate that using the RScore or RSPred as a constraint during molecular generation enables our molecular generators to produce more synthesizable solutions, with higher diversity. The open-source Python code containing all the scores and the experiments can be found on ( https://github.com/iktos/generation-under-synthetic-constraint ). Graphic Abstract

Sustainability management is a continuing process that must become an integral part of the business operations. Sustainability management is not a single act but a process. The site Sustainability Management [...]

A policy and Sustainability Management Program are not really useful unless the employees know about them and can take action to meet the targets. The employees can only do this [...]

We reported previously that in preclinical models, BMP4 is a potent inhibitor of breast cancer metastasis and that high BMP4 protein levels predict favourable patient outcomes. Here, we analysed a breast cancer xenograft with or without enforced expression of BMP4 to gain insight into the mechanisms by which BMP4 suppresses metastasis. Transcriptomic analysis of cancer cells recovered from primary tumours and phosphoproteomic analyses of cancer cells exposed to recombinant BMP4 revealed that BMP4 inhibits cholesterol biosynthesis, with many genes in this biosynthetic pathway being downregulated by BMP4. The treatment of mice bearing low-BMP4 xenografts with a cholesterol-lowering statin partially mimicked the anti-metastatic activity of BMP4. Analysis of a cohort of primary breast cancers revealed a reduced relapse rate for patients on statin therapy if their tumours exhibited low BMP4 levels. These findings indicate that BMP4 may represent a predictive biomarker for the benefit of additional statin therapy in breast cancer patients.

Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin’s role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in FURIN is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD.