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Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the most threatening infectious diseases worldwide. A series of challenges still exist for TB prevention, diagnosis and treatment, which therefore require more attempts to clarify the pathological and immunological mechanisms in the development and progression of TB. Circular RNAs (circRNAs) are a large class of non-coding RNA, mostly expressed in eukaryotic cells, which are generated by the spliceosome through the back-splicing of linear RNAs. Accumulating studies have identified that circRNAs are widely involved in a variety of physiological and pathological processes, acting as the sponges or decoys for microRNAs and proteins, scaffold platforms for proteins, modulators for transcription and special templates for translation. Due to the stable and widely spread characteristics of circRNAs, they are expected to serve as promising prognostic/diagnostic biomarkers and therapeutic targets for diseases. In this review, we briefly describe the biogenesis, classification, detection technology and functions of circRNAs, and, in particular, outline the dynamic, and sometimes aberrant changes of circRNAs in TB. Moreover, we further summarize the recent progress of research linking circRNAs to TB-related pathogenetic processes, as well as the potential roles of circRNAs as diagnostic biomarkers and miRNAs sponges in the case of Mtb infection, which is expected to enhance our understanding of TB and provide some novel ideas about how to overcome the challenges associated TB in the future. [ABSTRACT FROM AUTHOR]

Living materials combine a material scaffold, that is often porous, with engineered cells that perform sensing, computing, and biosynthetic tasks. Designing such systems is difficult because little is known regarding signaling transport parameters in the material. Here, the development of a porous microplate is presented. Hydrogel barriers between wells have a porosity of 60% and a tortuosity factor of 1.6, allowing molecular diffusion between wells. The permeability of dyes, antibiotics, inducers, and quorum signals between wells were characterized. A "sentinel" strain was constructed by introducing orthogonal sensors into the genome of Escherichia coli MG1655 for IPTG, anhydrotetracycline, L‐arabinose, and four quorum signals. The strain's response to inducer diffusion through the wells was quantified up to 14 mm, and quorum and antibacterial signaling were measured over 16 h. Signaling distance is dictated by hydrogel adsorption, quantified using a linear finite element model that yields adsorption coefficients from 0 to 0.1 mol m−3. Parameters derived herein will aid the design of living materials for pathogen remediation, computation, and self‐organizing biofilms. Synopsis: Microbes interact by chemical diffusion through materials, a concept that inspires "engineered living materials". To parameterize signaling through materials, a porous culture microplate is fabricated to measure chemical signaling between isolated wells of engineered E. coli. A porous microplate is fabricated by soft lithography of the co‐polymer hydroxyethyl methacrylate‐co‐ethylene glycol dimethacrylate.Four homoserine lactone quorum sensors are evolved to minimize cross‐talk via directed evolution.Seven total orthogonal sensors are encoded into the genome of E. coli MG1655, which serves as a "sentinel strain."The biological response of the sentinel strain to inducer, quorum, and antibiotic signaling between isolated wells of the microplate are experimentally measured.A quantitative model is developed that explains the difference in transport kinetics of the various biological signals by differential absorption of the molecules to the hydrogel matrix. [ABSTRACT FROM AUTHOR]

[Display omitted] • The in-situ gel of SPE ensures interface compatibility and scalable preparation. • InPc was conducive to improving ionic conductivity and suppressing shuttle effect. • InPc induces a protective layer on the surface of the lithium. • The resulting pouch Li-S cell delivered an energy density of 325.5 Wh kg−1. Lithium-sulfur batteries (LSBs) are currently being investigated as a potential candidate for high-energy–density rechargeable batteries. However, the notorious shuttle effect and uncontrolled dendrite growth posed problems for the practical applications of LSBs. Here, a new solid polymer electrolyte (SPE) was developed by in-situ polymerization of 1,3-dioxolane (DOL) in the presence of a multifunctional indium phthalocyanine (PDOL@InPc). The InPc endows the SPE with improved ionic conductivity and merit inhibition of the shuttle effect, in addition to being an effective additive for inducing uniform Li deposition by reconstructing the electric field at the interface. The characteristics of ionic migration in PDOL@InPc were quantified, and agreement between experiment and simulation established a relationship between macroscopic characteristics and molecular-level processes. The interfacial side reaction was controlled by the PDOL@InPc electrolyte, which also improved the distribution of the Li+ flux for dense Li deposition. Li symmetrical batteries designed with PDOL@lnPc can withstand a current density of up to 0.5 mA cm−2 and cycle reliably for 1500 h. The PDOL@InPc electrolyte displayed a high ionic conductivity at room temperature of 3.7 mS cm−1 and a significant Li+ transference number of 0.63. The resulting Li-S battery (Li|PDOL@lnPc|Sulfur) delivered a significant 325.5 Wh kg−1 of energy density at 0.2 C (1 C = 1000 mA g−1) at the level of the multilayer-pouch cell under an extremely low electrolyte of 3.5 g g−1 Sulfur and high loading of 8.0 mg cm−2. This work provides a feasible strategy for the widespread implementation of LSBs with increased safety and a longer lifetime. [ABSTRACT FROM AUTHOR]

DNA based synthetic molecular walkers are reminiscent of biological protein motors. They are powered by hybridization with fuel strands, environment induced conformational transitions, and covalent chemistry of oligonucleotides. Recent developments in experimental techniques enable direct observation of individual walkers with high temporal and spatial resolution. The functionalities of state-of-the-art DNA walker systems can thus be analyzed for various applications. Herein we review recent progress on DNA walker principles and characterization methods, and evaluate various aspects of their functions for future applications. [ABSTRACT FROM AUTHOR]