Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery.

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

Nickel Hydroxide-Based Electrocatalysts for Promising Electrochemical Oxidation Reactions: Beyond Water Oxidation.

Transition metal hydroxides have attracted significant research interest for their energy storage and conversion technique applications. In particular, nickel hydroxide (Ni(OH)2), with increasing significance, is extensively used in material science and engineering. The past decades have witnessed the flourishing of Ni(OH)2-based materials as efficient electrocatalysts for water oxidation, which is a critical catalytic reaction for sustainable technologies, such as water electrolysis, fuel cells, CO2 reduction, and metal-air batteries. Coupling the electrochemical oxidation of small molecules to replace water oxidation at the anode is confirmed as an effective and promising strategy for realizing the energy-saving production. The physicochemical properties of Ni(OH)2 related to conventional water oxidation are first presented in this review. Then, recent progress based on Ni(OH)2 materials for these promising electrochemical reactions is symmetrically categorized and reviewed. Significant emphasis is placed on establishing the structure-activity relationship and disclosing the reaction mechanism. Emerging material design strategies for novel electrocatalysts are also highlighted. Finally, the existing challenges and future research directions are presented.

Recent Progress of Low-Dimensional Metal-Organic Frameworks for Aqueous Zinc-Based Batteries.

Aqueous zinc-based batteries (AZBs) are promising energy storage solutions with remarkable safety, abundant Zn reserve, cost-effectiveness, and relatively high energy density. However, AZBs still face challenges such as anode dendrite formation that reduces cycling stability and limited cathode capacity. Recently, low-dimensional metal-organic frameworks (LD MOFs) and their derivatives have emerged as promising candidates for improving the electrochemical performance of AZBs owing to their unique morphologies, high structure tunability, high surface areas, and high porosity. However, clear guidelines for developing LD MOF-based materials for high-performance AZBs are scarce. In this review, the recent progress of LD MOF-based materials for AZBs is critically examined. The typical synthesis methods and structural design strategies for improving the electrochemical performance of LD MOF-based materials for AZBs are first introduced. The recent noteworthy research achievements are systematically discussed and categorized based on their applications in different AZB components, including cathodes, anodes, separators, and electrolytes. Finally, the limitations are addressed and the future perspectives are outlined for LD MOFs and their derivatives in AZB applications. This review provides clear guidance for designing high-performance LD MOF-based materials for advanced AZBs.

Advanced Applications of Porous Materials in Triboelectric Nanogenerator Self-Powered Sensors.

Porous materials possess advantages such as rich pore structures, a large surface area, low relative density, high specific strength, and good breathability. They have broad prospects in the development of a high-performance Triboelectric Nanogenerator (TENG) and self-powered sensing fields. This paper elaborates on the structural forms and construction methods of porous materials in existing TENG, including aerogels, foam sponges, electrospinning, 3D printing, and fabric structures. The research progress of porous materials in improving TENG performance is systematically summarized, with a focus on discussing design strategies of porous structures to enhance the TENG mechanical performance, frictional electrical performance, and environmental tolerance. The current applications of porous-material-based TENG in self-powered sensing such as pressure sensing, health monitoring, and human-machine interactions are introduced, and future development directions and challenges are discussed.

Synthetic microbial communities: Novel strategies to enhance the quality of traditional fermented foods.

Consumers are attracted to traditional fermented foods due to their unique flavor and nutritional value. However, the traditional fermentation technique can no longer accommodate the requirements of the food industry. Traditional fermented foods produce hazardous compounds, off-odor, and anti-nutritional factors, reducing product stability. The microbial system complexity of traditional fermented foods resulting from the open fermentation process has made it challenging to regulate these problems by modifying microbial behaviors. Synthetic microbial communities (SynComs) have been shown to simplify complex microbial communities and allow for the targeted design of microbial communities, which has been applied in processing traditional fermented foods. Herein, we describe the theoretical information of SynComs, particularly microbial physiological processes and their interactions. This paper discusses current approaches to creating SynComs, including designing, building, testing, and learning, with typical applications and fundamental techniques. Based on various traditional fermented food innovation demands, the potential and application of SynComs in enhancing the quality of traditional fermented foods are highlighted. SynComs showed superior performance in regulating the quality of traditional fermented foods using the interaction of core microorganisms to reduce the hazardous compounds of traditional fermented foods and improve flavor. Additionally, we presented the current status and future perspectives of SynComs for improving the quality of traditional fermented foods.

Recent Advances in Co-Based Electrocatalysts for Hydrogen Evolution Reaction.

Water splitting is a promising technique in the sustainable "green hydrogen" generation to meet energy demands of modern society. Its industrial application is heavily dependent on the development of novel catalysts with high performance and low cost for hydrogen evolution reaction (HER). As a typical non-precious metal, cobalt-based catalysts have gained tremendous attention in recent years and shown a great prospect of commercialization. However, the complexity of the composition and structure of newly-developed Co-based catalysts make it urgent to comprehensively retrospect and summarize their advance and design strategies. Hence, in this review, the reaction mechanism of HER is first introduced and the possible role of the Co component during electrocatalysis is discussed. Then, various design strategies that could effectively enhance the intrinsic activity are summarized, including surface vacancy engineering, heteroatom doping, phase engineering, facet regulation, heterostructure construction, and the support effect. The recent progress of the advanced Co-based HER electrocatalysts is discussed, emphasizing that the application of the above design strategies can significantly improve performance by regulating the electronic structure and optimizing the binding energy to the crucial intermediates. At last, the prospects and challenges of Co-based catalysts are shown according to the viewpoint from fundamental explorations to industrial applications.

Emerging Materials and Strategies for Passive Daytime Radiative Cooling.

In recent decades, the growing demands for energy saving and accompanying heat mitigation concerns, together with the vital goal for carbon neutrality, have drawn human attention to the zero-energy-consumption cooling technique. Recent breakthroughs in passive daytime radiative cooling (PDRC) might be a potent approach to combat the energy crisis and environmental challenges by directly dissipating ambient heat from the Earth to the cold outer space instead of only moving the heat across the Earth's surface. Despite significant progress in cooling mechanisms, materials design, and application exploration, PDRC faces potential functionalization, durability, and commercialization challenges. Herein, emerging materials and rational strategies for PDRC devices are reviewed. First, the fundamental physics and thermodynamic concepts of PDRC are examined, followed by a discussion on several categories of PDRC devices developed to date according to their implementation mechanism and material properties. Emerging strategies for performance enhancement and specific functions of PDRC are discussed in detail. Potential applications and possible directions for designing next-generation high-efficiency PDRC are also discussed. It is hoped that this review will contribute to exciting advances in PDRC and aid its potential applications in various fields.

Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.

Human society is facing the threat of various viruses. Proteases are promising targets for the treatment of viral infections. In this study, we collected and profiled 170 protease sequences from 125 viruses that infect humans. Approximately 73 of them are viral 3-chymotrypsin-like proteases (3CLpro), and 11 are pepsin-like aspartic proteases (PAPs). Their sequences, structures, and substrate characteristics were carefully analyzed to identify their conserved nature for proposing a pan-3CLpro or pan-PAPs inhibitor design strategy. To achieve this, we used computational prediction and modeling methods to predict the binding complex structures for those 73 3CLpro with 4 protease inhibitors of SARS-CoV-2 and 11 protease inhibitors of HCV. Similarly, the complex structures for the 11 viral PAPs with 9 protease inhibitors of HIV were also obtained. The binding affinities between these compounds and proteins were also evaluated to assess their pan-protease inhibition via MM-GBSA. Based on the drugs targeting viral 3CLpro and PAPs, repositioning of the active compounds identified several potential uses for these drug molecules. As a result, Compounds 1-2, modified based on the structures of Ray1216 and Asunaprevir, indicate potential inhibition of DENV protease according to our computational simulation results. These studies offer ideas and insights for future research in the design of broad-spectrum antiviral drugs.

Peripheralization Strategies Applied to Morphinans and Implications for Improved Treatment of Pain.

Opioids are considered the most effective analgesics for the treatment of moderate to severe acute and chronic pain. However, the inadequate benefit/risk ratio of currently available opioids, together with the current 'opioid crisis', warrant consideration on new opioid analgesic discovery strategies. Targeting peripheral opioid receptors as effective means of treating pain and avoiding the centrally mediated side effects represents a research area of substantial and continuous attention. Among clinically used analgesics, opioids from the class of morphinans (i.e., morphine and structurally related analogues) are of utmost clinical importance as analgesic drugs activating the mu-opioid receptor. In this review, we focus on peripheralization strategies applied to N-methylmorphinans to limit their ability to cross the blood-brain barrier, thus minimizing central exposure and the associated undesired side effects. Chemical modifications to the morphinan scaffold to increase hydrophilicity of known and new opioids, and nanocarrier-based approaches to selectively deliver opioids, such as morphine, to the peripheral tissue are discussed. The preclinical and clinical research activities have allowed for the characterization of a variety of compounds that show low central nervous system penetration, and therefore an improved side effect profile, yet maintaining the desired opioid-related antinociceptive activity. Such peripheral opioid analgesics may represent alternatives to presently available drugs for an efficient and safer pain therapy.

Interior designers' strategies for creating social office space.

The rise of remote working has highlighted the importance of office spaces that support employees' social well-being. However, there is a lack of explicit knowledge on how to design such spaces. In order to address this gap, this study explored the strategies employed by practitioners in designing social office spaces. In-depth interviews with fifteen experienced interior designers were analysed using means-end chain theory. This revealed the designers' common aim to encourage informal social interactions through creating attractive, spacious, recognisable, and spatially integrated breakout spaces. Additionally, communicating group identity, promoting visibility, and offering a cosy atmosphere aimed to foster a sense of connectedness among employees. These findings not only enable more deliberate design decisions but also serve as valuable insights for less experienced designers. Moreover, the framework of design components, affordances and design objectives that emerged from this study can enhance communication between designers and stakeholders involved in office projects.

Experienced interior designers were interviewed about completed office projects to understand how they design social offices. They shared five important strategies to enhance co-worker connectedness and eleven strategies to encourage informal social interactions at work. The study identified ten types of social workplace affordances along with their specific design attributes.

Toward Sustainable Metal-Iodine Batteries: Materials, Electrochemistry and Design Strategies.

Due to the natural abundance of iodine, cost-effective, and sustainability, metal-iodine batteries are competitive for the next-generation energy storage systems with high energy density, and large power density. However, the inherent properties of iodine such as electronic insulation and shuttle behavior of soluble iodine species affect negatively rate performance, cyclability, and self-discharge behavior of metal-iodine batteries, while the dendrite growth and metal corrosion on the anode side brings potential safety hazards and inferior durability. These problems of metal-iodine system still exist and need to be solved urgently. Herein, we summarize the research progress of metal-iodine batteries in the past decades. Firstly, the classification, design strategy and reaction mechanism of iodine electrode are briefly outlined. Secondly, the current development and protection strategy of conventional metal anodes in metal-iodine batteries are highlighted, and some potential anode materials and their design strategies are proposed. Thirdly, the key electrochemical parameters of state-of-art metal-iodine batteries are compared and analyzed to solve critical issues for realizing next-generation iodine-based energy storage systems. Therefore, the aim of this review is to promote the development of metal-iodine batteries and provide guidelines for their design.

Rational approaches towards inorganic and organometallic antibacterials.

The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in development are minor modifications of previously used drugs to which bacteria can easily develop resistance. The investigation of inorganic and organometallic compounds as antibiotics is an alternative approach that holds great promises due to the ability of such molecules to trigger metal-specific mechanisms of action, which results in lethal consequences for pathogens. In this review, a selection of concepts to rationally design inorganic and organometallic antibiotics is discussed, highlighting their advantages by comparing them to classical drug discovery programmes. The review concludes with a short perspective for the future of antibiotic drug development and the role metal-based compounds will play in the field.

Drug Delivery Strategies to Overcome the Blood-Brain Barrier (BBB).

The brain capillary endothelium serves both as an exchange site for gases and solutes between blood and brain and as a protective fence against neurotoxic compounds from the blood. While this "blood-brain barrier" (BBB) function protects the fragile environment in the brain, it also poses a tremendous challenge for the delivery of drug compounds to the brain parenchyma. Paracellular brain uptake of drug compounds is limited by the physical tightness of the endothelium, which is tightly sealed with junction complexes. Transcellular uptake of lipophilic drug compounds is limited by the activity of active efflux pumps in the luminal membrane. As a result, the majority of registered CNS drug compounds are small lipophilic compounds which are not efflux transporter substrates. Small molecule CNS drug development therefore focuses on identifying compounds with CNS target affinity and modifies these in order to optimize lipophilicity and decrease efflux pump interactions. Since efflux pump activity is limiting drug uptake, it has been investigated whether coadministration of drug compounds with efflux pump inhibitors could increase drug uptake. While the concept works to some extent, a lot of challenges have been encountered in terms of obtaining efficient inhibition while avoiding adverse effects.Some CNS drug compounds enter the brain via nutrient transport proteins, an example is the levodopa, a prodrug of Dopamine, which crosses the BBB via the large neutral amino acid transporter LAT1. While carrier-mediated transport of drug compounds may seem attractive, the development of drugs targeting transporters is very challenging, since the compounds should have a good fit to the binding site, while still maintaining their CNS target affinity.Receptor-mediated transport of drug compounds, especially biotherapeutics, conjugated to a receptor-binding ligand has shown some promise, although the amounts transported are rather low. This also holds true for drug-conjugation to cell-penetrating peptides. Due to the low uptake of biotherapeutics, barrier-breaching approaches such as mannitol injections and focused ultrasound have been employed with some success to patient groups with no other treatment options.

An analysis of design strategies for circular economy through life cycle assessment.

The goal of pursuing the circular economy (CE) is spreading more and more in industry, also driven by the introduction of new regulations, considerably affecting product design. However, a quantitative and rigorous evaluation of the environmental impacts of the results obtained by different design strategies used to implementing CE is missing in the literature. Those available only evaluate certain aspects of the life cycle of few products, belonging to specific application fields, in a qualitative way or they refer only to the global warming potential. This study provides a quantitative assessment of the environmental impacts reductions arising from the application of some common design strategies for implementing different CE options (e.g. reuse, waste to energy, remanufacturing), by using some standard indicators. The results were obtained by manually analysing 156 selected case studies of comparative life cycle assessment (LCA), extracted from 136 scientific articles. In them, the environmental impacts of design solutions for CE are compared with those of other solutions were wastes are not exploited. The obtained results have been used to evaluate the different design strategies for CE and to hierarchize them based on environmental sustainability of the solutions associated with them. In addition, an economic evaluation of the strategies, based on the life cycle costing methodology and exploiting the data available in the same articles, was also provided. Among the main achievements, it was found that the hierarchy of the CE options, pursued by the design strategies, to improve environmental sustainability is different from that provided by other studies. In addition, the environmental benefits associated with the different CE options strictly depend by the applied design strategies and the considered products.

Progress in Hydrogen Production Coupled with Electrochemical Oxidation of Small Molecules.

The electrochemical oxidation of small molecules to generate value-added products has gained enormous interest in recent years because of the advantages of benign operation conditions, high conversion efficiency and selectivity, the absence of external oxidizing agents, and eco-friendliness. Coupling the electrochemical oxidation of small molecules to replace oxygen evolution reaction (OER) at the anode and the hydrogen evolution reaction (HER) at the cathode in an electrolyzer would simultaneously realize the generation of high-value chemicals or pollutant degradation and the highly efficient production of hydrogen. This Minireview presents an introduction on small-molecule choice and design strategies of electrocatalysts as well as recent breakthroughs achieved in the highly efficient production of hydrogen. Finally, challenges and future orientations are highlighted.

Polymeric Carbon Nitride-Derived Photocatalysts for Water Splitting and Nitrogen Fixation.

Photocatalysis is a promising energy conversion and environmental restoration technology. The main focus of photocatalysis is the development and manufacture of highly efficient photocatalysts. Semiconductor-based photocatalysis technology based on harnessing solar energy is considered as an attractive approach to solve the problems of global energy shortage and environmental pollution. Since 2009 pioneering work has been carried out on polymeric carbon nitride (PCN) for visible photocatalytic water splitting, thus PCN-based photocatalysis has become a hot research topic, demanding significant research attention. This article reviews the physical and chemical properties, synthesis methods, and the methods to control the morphology, heteroatom doping, and construction of heterojunctions to improve the performance of PCN-based photocatalysts in water splitting and nitrogen fixation. Through different design strategies, the photo-generated electron-hole pair separation efficiency of PCN materials can be effectively improved, thereby improving their photocatalytic performance. Finally, the challenges of PCN-based photocatalysts in water splitting and nitrogen fixation applications are discussed herein. It is strongly believed that through different design strategies, efficient PCN-based photocatalysts can be constructed for both water splitting and nitrogen reduction. These excellent modification strategies can be used as a guiding theory for photocatalytic reactions of other promising catalysts and further promote the development of photocatalysis.

Correlating Catalyst Design and Discharged Product to Reduce Overpotential in Li-CO2 Batteries.

Li-CO2 batteries with dual efficacy for greenhouse gas CO2 sequestration and high energy output have been regarded as a promising electrochemical energy storage technology. However, battery feasibility has been hampered by inferior electrochemical performance due to large overpotentials and low cyclability primarily caused by the difficult decomposition of ultra-stable Li2 CO3 during charge. The use of cathode catalysts has been highlighted as a promising solution and catalyst properties, as well as the nature of discharge products, are closely correlated with electrochemical performance. Here, the catalyst design strategies that include active site enrichment, electrical transport enhancement, and mass transfer improvement are summarized. Catalyst effects on product decomposition are then subsequently introduced, while product geometry and chemical composition will be explored, with an emphasis on the formation/decomposition of Li2 C2 O4 instead of Li2 CO3 . Building on previous research, future directions that facilitate improvements in catalyst design are put forward to reinforce the fundamental development of Li-CO2 batteries.

miPrimer: an empirical-based qPCR primer design method for small noncoding microRNA.

MicroRNAs (miRNAs) are 18-25 nucleotides (nt) of highly conserved, noncoding RNAs involved in gene regulation. Because of miRNAs' short length, the design of miRNA primers for PCR amplification remains a significant challenge. Adding to the challenge are miRNAs similar in sequence and miRNA family members that often only differ in sequences by 1 nt. Here, we describe a novel empirical-based method, miPrimer, which greatly reduces primer dimerization and increases primer specificity by factoring various intrinsic primer properties and employing four primer design strategies. The resulting primer pairs displayed an acceptable qPCR efficiency of between 90% and 110%. When tested on miRNA families, miPrimer-designed primers are capable of discriminating among members of miRNA families, as validated by qPCR assays using Quark Biosciences' platform. Of the 120 miRNA primer pairs tested, 95.6% and 93.3% were successful in amplifying specifically non-family and family miRNA members, respectively, after only one design trial. In summary, miPrimer provides a cost-effective and valuable tool for designing miRNA primers.

A painful lesson from the COVID-19 pandemic: the need for broad-spectrum, host-directed antivirals.

While the COVID-19 pandemic has spurred intense research and collaborative discovery worldwide, the development of a safe, effective, and targeted antiviral from the ground up is time intensive. Therefore, most antiviral discovery efforts are focused on the re-purposing of clinical stage or approved drugs. While emerging data on drugs undergoing COVID-19 repurpose are intriguing, there is an undeniable need to develop broad-spectrum antivirals to prevent future viral pandemics of unknown origin. The ideal drug to curtail rapid viral spread would be a broad-acting agent with activity against a wide range of viruses. Such a drug would work by modulating host-proteins that are often shared by multiple virus families thereby enabling preemptive drug development and therefore rapid deployment at the onset of an outbreak. Targeting host-pathways and cellular proteins that are hijacked by viruses can potentially offer broad-spectrum targets for the development of future antiviral drugs. Such host-directed antivirals are also likely to offer a higher barrier to the development and selection of drug resistant mutations. Given that most approved antivirals do not target host-proteins, we reinforce the need for the development of such antivirals that can be used in pre- and post-exposure populations.

Design of High-Performance Co-Based Alloy Nanocatalysts for the Oxygen Reduction Reaction.

Co-based nanoalloys show potential applications as nanocatalysts for the oxygen reduction reaction (ORR), but improving their activity is still a great challenge. In this paper, a strategy is proposed to design efficient Co-M (M=Au, Ag, Pd, Pt, Ir, and Rh) nanoalloys as ORR catalysts by using density functional theory (DFT) calculations. Through the Sabatier analysis, the overpotential as a function of ΔGOH * is identified as a quantitative descriptor for analyzing the effect of dopants and atomic structures on the activity of the Co-based nanoalloys. By adopting the suitable dopants and atomic structures, ΔGOH * accompanied by overpotential could be adjusted to the optimal range to enhance the activity of the Co-based nanoalloys. With this strategy, the core-shell structured Ag42 Co13 nanoalloy is predicted to have the highest catalytic activity for ORR among these Co-based nanoalloys. To give a deeper insight into the properties of Ag-Co nanoalloys, the structure, thermal stability, and reaction mechanism of Ag-Co nanoalloys with different compositions are also studied by using molecular simulations and DFT calculations. It is found that core-shell Ag42 Co13 exhibits the highest structural and thermal stability among these Ag-Co nanoalloys. In addition, the core-shell Ag42 Co13 shows the lowest ORR reaction energy barriers among these Ag-Co nanoalloys. It is expected that this kind of strategy could provide a viable way to design highly efficient heterogeneous catalysts in extensive applications.