Forward Look Research Articles

To infinity and beyond: Strategies for fabricating medicines in outer space

Recent advancements in next generation spacecrafts have reignited public excitement over life beyond Earth. However, to safeguard the health and safety of humans in the hostile environment of space, innovation in pharmaceutical manufacturing and drug delivery deserves urgent attention. In this review/commentary, the current state of medicines provision in space is explored, accompanied by a forward look on the future of pharmaceutical manufacturing in outer space. The hazards associated with spaceflight, and their corresponding medical problems, are first briefly discussed. Subsequently, the infeasibility of present-day medicines provision systems for supporting deep space exploration is examined. The existing knowledge gaps on the altered clinical effects of medicines in space are evaluated, and suggestions are provided on how clinical trials in space might be conducted. An envisioned model of on-site production and delivery of medicines in space is proposed, referencing emerging technologies (e.g. Chemputing, synthetic biology, and 3D printing) being developed on Earth that may be adapted for extra-terrestrial use. This review concludes with a critical analysis on the regulatory considerations necessary to facilitate the adoption of these technologies and proposes a framework by which these may be enforced. In doing so, this commentary aims to instigate discussions on the pharmaceutical needs of deep space exploration, and strategies on how these may be met.

Quantum Dot-Antibody Conjugates for Immunofluorescence Studies of Biomolecules and Subcellular Structures.

Quantum dots, or nanoscale semiconductors, are one of the most important materials for various research and development purposes. Due to their advantageous photoluminescence and electronic properties, namely, their unique photostability, high brightness, narrow emission spectra from visible to near-infrared wavelengths, convey them significant advantages over widely used fluorochromes, including organic dyes, fluorescent probes. Quantum dots are a unique instrument for a wide range of immunoassays with antibodies. The paper provides an overview of the developed and already applied methods of quantum dot surface modification, quantum dots conjugation to different antibodies (non-covalent, direct covalent linkage or with the use of special adapter molecules), as well as practical examples of recent quantum dot-antibody applications in the immunofluorescence microscopy for cell and cell structure imaging, fluorescent assays for biomolecules detection and in diagnostics of various diseases. The review presents advantages of quantum dot-antibody conjugation technology over the existing methods of immunofluorescence studies and a forward look into its potential prospects in biological and biomedical research.

The composites of triple-helix glucan nanotubes/selenium nanoparticles target hepatocellular carcinoma to enhance ferroptosis by depleting glutathione and augmenting redox imbalance

Exacerbating oxidative stress has become a promising strategy for effective cancer therapy. However, the hyperactive antioxidant systems in tumor cells neutralize this effect, reducing potency and promoting drug resistance. Herein, we put forward a new insight into the cancer therapy by depleting glutathione (GSH) and inducing cellular redox imbalance based on selenium nanoparticles (SeNPs)-loaded β-glucan nanotube (BFP-Se) composed of natural triple-helix glucans, derived from black fungus. BFP-Se targeted tumor tissues through enhanced permeability and retention effects, enhancing the bioavailability of SeNPs. Metabolomics unveiled that BFP-Se related metabolic responses were mainly associated with oxidative stress in hepatoma cells. In vivo and in vitro experiments prove that BFP-Se effectively depleted the intracellular GSH, inhibited TXNIP/TRX and NRF2/GPX4-associated antioxidant systems expressions, while produced reactive oxygen species by reacting with intracellular H2O2, ultimately leading to apoptosis and ferroptosis of hepatoma cells. This work offers a deeper understanding of nanomedicine-bio interactions and provides a forward look at cancer therapy by depleting GSH and inducing cellular redox imbalance.

Recent Advancements in the Fabrication of Functional Nanoporous Materials and Their Biomedical Applications.

Functional nanoporous materials are categorized as an important class of nanostructured materials because of their tunable porosity and pore geometry (size, shape, and distribution) and their unique chemical and physical properties as compared with other nanostructures and bulk counterparts. Progress in developing a broad spectrum of nanoporous materials has accelerated their use for extensive applications in catalysis, sensing, separation, and environmental, energy, and biomedical areas. The purpose of this review is to provide recent advances in synthesis strategies for designing ordered or hierarchical nanoporous materials of tunable porosity and complex architectures. Furthermore, we briefly highlight working principles, potential pitfalls, experimental challenges, and limitations associated with nanoporous material fabrication strategies. Finally, we give a forward look at how digitally controlled additive manufacturing may overcome existing obstacles to guide the design and development of next-generation nanoporous materials with predefined properties for industrial manufacturing and applications.

Improvements and advances in core outcome set methodology: proceedings of the CS-COUSIN & COMFA Joint Meeting.

A COS is a systematically developed list of outcomes recommended for reporting all studies within a particular disease area. The Cochrane Skin–Core Outcome Set Initiative (CS-COUSIN) and the Core Outcome Measures in Food Allergy (COMFA) Initiative Joint Meeting was held virtually on September 23 through 28, 2021. This meeting brought together core outcome set (COS) developers within the domains of dermatology and food allergy, respectively. The meeting assessed the state of COS methodology, provided a forward look, and facilitated the networking of members of individual COS groups. The meeting hosted several expert-led key addresses and focus sessions, in which work was critically discussed, new developments were shared, and groundwork was laid for future projects. The conference emphasized the importance of ongoing COS work to improve patient outcomes and limit research waste.

Trends in coordination of rhenium organometallic complexes in the Protein Data Bank.

Radiopharmaceutical development has similar overall characteristics to any biomedical drug development requiring a compound's stability, aqueous solubility and selectivity to a specific disease site. However, organometallic complexes containing 188/186Re or 99mTc involve a d-block transition-metal radioactive isotope and therefore bring additional factors such as metal oxidation states, isotope purity and half life into play. This topical review is focused on the development of radiopharmaceuticals containing the radioisotopes of rhenium and technetium and, therefore, on the occurrence of these organometallic complexes in protein structures in the Worldwide Protein Data Bank (wwPDB). The purpose of incorporating the group 7 transition metals of rhenium/technetium in the protein and the reasons for study by protein crystallography are described, as certain PDB studies were not aimed at drug development. Technetium is used as a medical diagnostic agent and involves the 99mTc isotope which decays to release gamma radiation, thereby employed for its use in gamma imaging. Due to the periodic relationship among group 7 transition metals, the coordination chemistry of rhenium is similar (but not identical) to that of technetium. The types of reactions the potential model radiopharmaceutical would prefer to partake in, and by extension knowing which proteins and biomolecules the compound would react with in vivo, are needed. Crystallography studies, both small molecule and macromolecular, are a key aspect in understanding chemical coordination. Analyses of bonding modes, coordination to particular residues and crystallization conditions are presented. In our Forward look as a concluding summary of this topical review, the question we ask is: what is the best way for this field to progress?

Recent results and perspectives for virtual element methods

This editorial paper is devoted to present the papers published in a special issue focused on recent views, applications, and results of virtual element methods (VEM). A critical analysis of the overall contents of the issue is proposed, thus leading to a forward look to research perspectives.

Modeling virus pandemics in a globally connected world a challenge towards a mathematics for living systems

This editorial paper presents the papers published in a special issue devoted to the modeling and simulation of mutating virus pandemics in a globally connected world. The presentation is proposed in three parts. First, motivations and objectives are presented according to the idea that mathematical models should go beyond deterministic population dynamics by considering the multiscale, heterogeneous features of the complex system under consideration. Subsequently, the contents of the papers in this issue are presented referring to the aforementioned complexity features. Finally, a critical analysis of the overall contents of the issue is proposed, with the aim of providing a forward look to research perspectives.

Obstacles and opportunities in a forward vision for cancer nanomedicine.

Cancer nanomedicines were initially envisioned as magic bullets, travelling through the circulation to target tumours while sparing healthy tissues the toxicity of classic chemotherapy. While a limited number of nanomedicine therapies have resulted, the disappointing news is that major obstacles were overlooked in the nanoparticle's journey. However, some of these challenges may be turned into opportunities. Here, we discuss biological barriers to cancer nanomedicines and elaborate on two directions that the field is currently exploring to meet its initial expectations. The first strategy entails re-engineering cancer nanomedicines to prevent undesired interactions en route to the tumour. The second aims instead to leverage these obstacles into out-of-the-box diagnostic and therapeutic applications of nanomedicines, for cancer and beyond. Both paths require, among other developments, a deeper understanding of nano-bio interactions. We offer a forward look at how classic cancer nanomedicine may overcome its limitations while contributing to other areas of research.

Medical management of endometriosis.

Endometriosis is a benign gynecologic disorder that is defined as functional endometrial tissue outside of the uterine cavity. It is an estrogen-dependent, inflammatory disease that leads to symptoms of pelvic pain, dysmenorrhea, dyspareunia, and infertility, occurring in 6-10% of reproductive aged women. The severity of the disease ranges from asymptomatic to debilitating symptoms that have a major impact on women's lives. It is a chronic, recurrent disease, frequently requiring long term management until menopause and beyond. It is considered a chronic disorder that is managed with surgery, medical treatment, and oftentimes, both. Current medical therapy for endometriosis is considered suppressive of the disease, rather than curative. Fortunately, many patients do experience improvement and control of their symptoms with medical therapy. However, long-term efficacy of the medical treatments is often limited by side effects and the cost of therapy, and symptoms do tend to recur after discontinuation of these medications. This review summarizes our understanding of the pathogenesis of endometriosis and provides more in-depth discussion of specific medical management options used to treat endometriosis, including mechanism of action and side effects. It also provides recommendations on strategy with a forward look to novel endometriosis treatments in the future. The authors emphasized that endometriosis is a chronic disorder requiring long term medical therapy. Early diagnosis of endometriosis is key in preventing severe, debilitating symptoms and progression of disease. By utilizing our current knowledge of the pathophysiology of endometriosis and by correctly implementing currently available medical and surgical therapies we can significantly reduce the physical, psychosocial and financial burden of this chronic, recurrent and indolent disease. Current available medications are suppressive therapies, but the authors are looking forward to future therapies that can effectively cure or at least control endometriosis with minimal side effects. Future research should continue to look for the genetic trigger for endometriosis which can lead us to its underlying pathogenesis and eventually a cure or prevention.

Collective dynamics in science and society

This editorial paper presents the articles published in a special issue devoted to active particle methods applied to modeling, qualitative analysis, and simulation of the collective dynamics of large systems of interacting living entities in science and society. The modeling approach refers to the mathematical tools of behavioral swarms theory and to the kinetic theory of active particles. Applications focus on classical problems of swarms theory, on crowd dynamics related to virus contagion problems, and to multiscale problems related to the derivation of models at a large scale from the mathematical description at the microscopic scale. A critical analysis of the overall contents of the issue is proposed, with the aim to provide a forward look to research perspectives.

A review of turbulent skin-friction drag reduction by near-wall transverse forcing

The quest for reductions in fuel consumption and CO2 emissions in transport has been a powerful driving force for scientific research into methods that might underpin drag-reducing technologies for a variety of vehicular transport on roads, by rail, in the air, and on or in the water. In civil aviation, skin-friction drag accounts for around 50% of the total drag in cruise conditions, thus being a preferential target for research. With laminar conditions excluded, skin friction is intimately linked to the turbulence physics in the fluid layer closest to the skin. Hence, research into drag reduction has focused on methods to depress the turbulence activity near the surface. The most effective method of doing so is to exercise active control on the near-wall layer by subjecting the drag-producing flow in this layer to an unsteady and/or spatially varying cross-flow component, either by the action of transverse wall oscillations, by embedding rotating discs into the surface or by plasma-producing electrodes that accelerate the near-wall fluid in the transverse direction. In ideal conditions, drag-reduction margins of order of 50% can thereby be achieved. The present article provides a near-exhaustive review of research into the response of turbulent near-wall layers to the imposition of unsteady and wavy transverse motion. The review encompasses experiments, simulation, analysis and modelling, mainly in channel flows and boundary layers. It covers issues such as the drag-reduction margin in a variety of actuation scenarios and for a wide range of actuation parameters, the underlying physical phenomena that contribute to the interpretation of the origin of the drag reduction, the dependence of the drag reduction on the Reynolds number, passive control methods that are inspired by active control, and a forward look towards possible future research and practical realizations. The authors hope that this review, by far the most extensive of its kind for this subject, will be judged as a useful foundation for future research targeting friction-drag reduction.

Alkaloids Used as Medicines: Structural Phytochemistry Meets Biodiversity-An Update and Forward Look.

Selecting candidates for drug developments using computational design and empirical rules has resulted in a broad discussion about their success. In a previous study, we had shown that a species’ abundance [as expressed by the GBIF (Global Biodiversity Information Facility)] dataset is a core determinant for the development of a natural product into a medicine. Our overarching aim is to understand the unique requirements for natural product-based drug development. Web of Science was queried for research on alkaloids in combination with plant systematics/taxonomy. All alkaloids containing species demonstrated an average increase of 8.66 in GBIF occurrences between 2014 and 2020. Medicinal Species with alkaloids show higher abundance compared to non-medicinal alkaloids, often linked also to cultivation. Alkaloids with high biodiversity are often simple alkaloids found in multiple species with the presence of ’driver species‘ and are more likely to be included in early-stage drug development compared to ‘rare’ alkaloids. Similarly, the success of an alkaloid containing species as a food supplement (‘botanical’) is linked to its abundance. GBIF is a useful tool for assessing the druggability of a compound from a certain source species. The success of any development programme from natural sources must take sustainable sourcing into account right from the start.

Electrodeposited Hydroxyapatite-Based Biocoatings: Recent Progress and Future Challenges

Hydroxyapatite has become an important coating material for bioimplants, following the introduction of synthetic HAp in the 1950s. The HAp coatings require controlled surface roughness/porosity, adequate corrosion resistance and need to show favorable tribological behavior. The deposition rate must be sufficiently fast and the coating technique needs to be applied at different scales on substrates having a diverse structure, composition, size, and shape. A detailed overview of dry and wet coating methods is given. The benefits of electrodeposition include controlled thickness and morphology, ability to coat a wide range of component size/shape and ease of industrial processing. Pulsed current and potential techniques have provided denser and more uniform coatings on different metallic materials/implants. The mechanism of HAp electrodeposition is considered and the effect of operational variables on deposit properties is highlighted. The most recent progress in the field is critically reviewed. Developments in mineral substituted and included particle, composite HAp coatings, including those reinforced by metallic, ceramic and polymeric particles; carbon nanotubes, modified graphenes, chitosan, and heparin, are considered in detail. Technical challenges which deserve further research are identified and a forward look in the field of the electrodeposited HAp coatings is taken.

Quantitative plant biology-Old and new.

Quantitative approaches in plant biology have a long history that have led to several ground-breaking discoveries and given rise to new principles, new paradigms and new methodologies. We take a short historical trip into the past to explore some of the many great scientists and influences that have led to the development of quantitative plant biology. We have not been constrained by historical fact, although we have tried not to deviate too much. We end with a forward look, expressing our hopes and ambitions for this exciting interdisciplinary field.

Silk Road: A Journal of Eurasian Development – Prospectus and Purpose

This editorial explains the beginnings of the journal Silk Road commencing around the time of the 2019 Tashkent agreement and the journal’s future scope and ambitions. As nations within Central Asia look towards greater cooperation the editors articulate the journal’s focus on public policy issues and how Silk Road intends to offer a long-held need for scholarly perspectives and analysis from within the region itself. It explains how the journal’s name links to the past of the region, to evoke its ‘inclusive’ connotations as a space of exchange, travel and ‘ambiguity’ but also is ‘intended to evoke a dynamic forward look towards the future’. Embodying a broad and interdisciplinary focus in its scope, it is hoped that the journal’s name also paves the way to its long term mission of encouraging ‘creativity among researchers working’ on policy in the region and to ‘prompt them both to analyse current public policy and to imagine its future’.

Recent results and challenges in behavioral systems

This editorial paper is devoted to present the papers published in a special issue focused on modeling, qualitative analysis and simulation of the collective dynamics of living, self-propelled particles. A critical analysis of the overall contents of the issue is proposed, thus leading to a forward look to research perspectives.

Special Issue “Kinetic Theory and Swarming Tools to Modeling Complex Systems—Symmetry problems in the Science of Living Systems”—Editorial and Research Perspectives

This editorial paper presents a special issue devoted to the development of mathematical tools from kinetic and swarms theory to the modeling and simulations of the dynamics of living systems constituted by very many interacting living entities. Applications refer to several fields: collective learning, behavioral economy, multicellular systems, vehicular traffic, and human crowds. A forward look to research perspectives is focused on the conceptual links between swarms methods and the kinetic theory approach.

Social Data: CESSDA Best Practices

The European Commission report “Turning FAIR into reality” provides an index of 27 FAIR Action Plan recommendations. This index is used for a self-assessment on CESSDA, the Consortium of European Social Science Data Archives. CESSDA is performing well on “Concepts for FAIR implementation”, “Skills for FAIR”, and “Investment in FAIR”; there is work in progress on “FAIR culture”, and work to start up on “FAIR ecosystem” and especially on “Incentives and metrics for FAIR data and services”. Next, an analysis on the FAIR components, reveals that CESSDA has accomplished the “F”, is working on the “A” – considering the sensitivity and security requirements of social data, just started on “I”, and that there is lack of clarity on what should be in “R”. On Findability, the CESSDA Data Catalogue is explained, showing the building blocks that need to be in place before one can produce a catalogue. The article ends with a forward look on CESSDA's deployment on the FAIR principles.

The Role of Magnetic Fields in Protostellar Outflows and Star Formation

The role of outflows in the formation of stars and the protostellar disks that generate them is a central question in astrophysics. Outflows are associated with star formation across the entire stellar mass spectrum. In this review, we describe the observational, theoretical, and computational advances on magnetized outflows, and their role in the formation of disks and stars of all masses in turbulent, magnetized clouds. The ability of torques exerted on disks by magnetized winds to efficiently extract and transport disk angular momentum was developed in early theoretical models and confirmed by a variety of numerical simulations. The recent high resolution ALMA observations of disks and outflows now confirm several key aspects of these ideas, e.g. that jets rotate and originate from large regions of their underlying disks. New insights on accretion disk physics show that magneto-rotational instability (MRI) turbulence is strongly damped, leaving magnetized disk winds as the dominant mechanism for transporting disk angular momentum. This has major consequences for star formation, as well as planet formation. Outflows also play an important role in feedback processes particularly in the birth of low mass stars and cluster formation. Despite being almost certainly fundamental to their production and focusing, magnetic fields in outflows in protostellar systems, and even in the disks, are notoriously difficult to measure. Most methods are indirect and lack precision, as for example, when using optical/near-infrared line ratios. Moreover, in those rare cases where direct measurements are possible - where synchrotron radiation is observed, one has to be very careful in interpreting derived values. Here we also explore what is known about magnetic fields from observations, and take a forward look to the time when facilities such as SPIRou and the SKA are in routine operation.