Structural insights into the diversity and DNA cleavage mechanism of Fanzor.

Fanzor (Fz) is an ωRNA-guided endonuclease extensively found throughout the eukaryotic domain with unique gene editing potential. Here, we describe the structures of Fzs from three different organisms. We find that Fzs share a common ωRNA interaction interface, regardless of the length of the ωRNA, which varies considerably across species. The analysis also reveals Fz's mode of DNA recognition and unwinding capabilities as well as the presence of a non-canonical catalytic site. The structures demonstrate how protein conformations of Fz shift to allow the binding of double-stranded DNA to the active site within the R-loop. Mechanistically, examination of structures in different states shows that the conformation of the lid loop on the RuvC domain is controlled by the formation of the guide/DNA heteroduplex, regulating the activation of nuclease and DNA double-stranded displacement at the single cleavage site. Our findings clarify the mechanism of Fz, establishing a foundation for engineering efforts.

Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex.

Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the human CB2-Gi signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals the binding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonists from antagonists, which are supported by a pair of rationally designed agonist and antagonist. Further structural analyses with computational docking results uncover the differences between CB2 and CB1 in receptor activation, ligand recognition, and Gi coupling. These findings are expected to facilitate rational structure-based discovery of drugs targeting the cannabinoid system.

Structure-based insights into fluorogenic RNA aptamers.

Fluorogenic RNA aptamers are in vitro-selected RNA molecules capable of binding to specific fluorophores, significantly increasing their intrinsic fluorescence. Over the past decade, the color palette of fluorescent RNA aptamers has greatly expanded. The emergence and development of these fluorogenic RNA aptamers has introduced a powerful approach for visualizing RNA localization and transport with high spatiotemporal resolution in live cells. To date, a variety of tertiary structures of fluorogenic RNA aptamers have been determined using X-ray crystallography or NMR spectroscopy. Many of these fluorogenic RNA aptamers feature base quadruples or base triples in their fluorophore-binding sites. This review summarizes the structure-based investigations of fluorogenic RNA aptamers, with a focus on their overall folds, ligand-binding pockets and fluorescence activation mechanisms. Additionally, the exploration of how structures guide rational optimization to enhance RNA visualization techniques is discussed.

Research Progress on the Degradation of Organic Pollutants in Wastewater via Ultrasound/Periodate Systems: A Review.

In recent years, the efficient removal of organic pollutants from wastewater has emerged as a critical area of global research interest. Against this backdrop, an array of innovative technologies for wastewater treatment has been developed. Among numerous advanced oxidation processes (AOPs), periodate (PI), an emerging oxidizing agent in AOPs, has garnered significant attention from researchers. Particularly, the integration of ultrasound (US)-activated PI systems has been recognized as an exceptionally promising approach for the synergistic degradation of organic pollutants in wastewater. In this paper, we conducted a thorough analysis of the mechanisms underlying the degradation of organic pollutants using the US/PI system. Furthermore, we comprehensively delineated the effects of ultrasonic power, periodate concentration, temperature, pH, coexisting inorganic ions, and dissolved organic matter on the removal efficiency of organic pollutants and summarized application cases of the US/PI system for the degradation of different pollutants. Finally, we also offered prospective discussions on the future trajectories of US/PI technology development.

A simple yet multifaceted 90 years old, evergreen enzyme: Carbonic anhydrase, its inhibition and activation.

Advances in the carbonic anhydrase (CA, EC 4.2.1.1) research over the last three decades are presented, with an emphasis on the deciphering of the activation mechanism, the development of isoform-selective inhibitors/ activators by the tail approach and their applications in the management of obesity, hypoxic tumors, neurological conditions, and as antiinfectives.

Sulfate radicals-based advanced oxidation processes for the degradation of pharmaceuticals and personal care products: A review on relevant activation mechanisms, performance, and perspectives.

Owing to the rapid development of modern industry, a greater number of organic pollutants are discharged into the water matrices. In recent decades, research efforts have focused on developing more effective technologies for the remediation of water containing pharmaceuticals and personal care products (PPCPs). Recently, sulfate radicals-based advanced oxidation processes (SR-AOPs) have been extensively used due to their high oxidizing potential, and effectiveness compared with other AOPs in PPCPs remediation. The present review provides a comprehensive assessment of the different methods such as heat, ultraviolet (UV) light, photo-generated electrons, ultrasound (US), electrochemical, carbon nanomaterials, homogeneous, and heterogeneous catalysts for activating peroxymonosulfate (PMS) and peroxydisulfate (PDS). In addition, possible activation mechanisms from the point of radical and non-radical pathways are discussed. Then, biodegradability enhancement and toxicity reduction are highlighted. Comparison with other AOPs and treatment of PPCPs by the integrated process are evaluated as well. Lastly, conclusions and future perspectives on this research topic are elaborated.

Polyethylene-Derived Activated Carbon Materials for Commercially Available Supercapacitor in an Organic Electrolyte System.

High-performance supercapacitors based on activated carbons (AC) derived from polyethylene (PE), which is one of the most abundant plastic materials worldwide, are fabricated. First, PE carbons (PEC) are prepared via sulfonation, which is a reported solution for successful carbonization of innately non-carbonizable PE. Then, the physico-electrical changes of PECs upon a chemical activation process are explored. Interestingly, upon the chemical activation, PECs are converted ACs with a large surface area and high crystallinity at the same time. Subsequently, PE-derived ACs (PEAC) are exploited as electrode materials for supercapacitors. Resultant supercapacitors based on PEACs exhibit impressive performance. When compared to supercapacitors based on YP50f, representative commercial ACs, devices using PEACs presented considerably good capacitance, low resistance, and great rate capability. Specifically, the retention rate of devices using PEACs is significantly higher than that of YP50f-based devices. At the high rate of charge-discharge situation reaching 7 A g-1 , the capacitance of supercapacitors using PEACs is ≈70% higher than that of YP50f-based devices. It is assumed that the carbon structure accompanying both large surface area and high conductivity endows a great electrochemical performance at the high current operating conditions. Therefore, it is envisioned that PE may be a viable candidate electrode material for commercially available supercapacitors.

Structural and Functional Analysis of Sodium Channels Viewed from an Evolutionary Perspective.

Voltage-gated sodium channels initiate and propagate action potentials in excitable cells. They respond to membrane depolarization through opening, followed by fast inactivation that terminates the sodium current. This ON-OFF behavior of voltage-gated sodium channels underlays the coding of information and its transmission from one location in the nervous system to another. In this review, we explore and compare structural and functional data from prokaryotic and eukaryotic channels to infer the effects of evolution on sodium channel structure and function.

Sensory irritation of vapours of formic, acetic, propionic and butyric acid.

In mice, inhalation of formic, acetic, propionic and butyric acid caused a rapid decrease in the respiratory rate, which decreased to a stable level during the remaining part of the 30 min exposure period; this was due to sensory irritation. The concentration decreasing the respiratory rate (RD) by 50% (RD50) was 438, 308, 386 and 285 ppm, respectively, which allowed an adequate prediction of the Threshold Limit Values. In mice inhaling through a tracheal cannula, bypassing the trigeminal nerves, caused a slower decrease in respiratory rate due to pulmonary irritation. In the low concentration range, the pulmonary irritation response was less pronounced than the sensory irritation response. As the response in the normal (non-cannulated) mice was not influenced by pulmonary irritation, sensory irritation is the key effect, presumably due to the scrubbing effect of the upper airways, preventing access to the lungs. The activated receptors were in a non-lipophilic (hydrophilic) environment, from where the receptors may be activated by means of liberated protons. At the RD0, formic acid may, at least partly, activates ASIC, TRPV1 and TRPA1 receptors, whereas acetic, propionic and butyric acid may activate ASIC and TRPA1 receptors, based on the estimated pH in the mucus layer.

A critical review of persulfate-based electrochemical advanced oxidation processes for the degradation of emerging contaminants: From mechanisms and electrode materials to applications.

The persulfate-based electrochemical advanced oxidation processes (PS-EAOPs) exhibit distinctive advantages in the degradation of emerging contaminants (ECs) and have garnered significant attention among researchers, leading to a consistent surge in related research publications over the past decade. Regrettably, there is still a lack of a critical review gaining deep into understanding of ECs degradation by PS-EAOPs. To address the knowledge gaps, in this review, the mechanism of electro-activated PS at the interface of the electrodes (anode, cathode and particle electrodes) is elaborated. The correlation between these electrode materials and the activation mechanism of PS is systematically discussed. The strategies for improving the performance of electrode material that determining the efficiency of PS-EAOPs are also summarized. Then, the applications of PS-EAOPs for the degradation of ECs are described. Finally, the challenges and outlook of PS-EAOPs are discussed. In summary, this review offers valuable guidance for the degradation of ECs by PS-EAOPs.

Atomically dispersed cobalt activator with nitrogen and sulfur co-coordination for high-efficiency Fenton-like catalysis: Insights into density-dependent activity and mechanisms.

Atomically dispersed metal activators (ADMAs) have demonstrated unique advantages in environmental remediation, but how to controllably regulate the active site density and electronic structure of ADMAs to further enhance activation efficiency remains challenging. Here, we introduce a sulfur-atom-doping approach that allows the fine-tuning of atomic Co site content and electronic structure, enabling exploration of density-dependent activation performance of ADMAs for peroxymonosulfate (PMS)-based Fenton-like catalysis. Our investigation reveals a direct correlation between activation capacity and single-Co-site density. The optimal SNC@CoSA-0.05 activator with densely populated Co-N3S1 sites (10.1 wt%) displays exceptional efficacy in eliminating Rhodamine B, with specific activity of 31.0 min-1 g-1 L, outperforming most previously published activators. Moreover, SNC@CoSA-0.05 showed a remarkedly reduced metal leaching (47.4 µg L-1) than its nanocluster counterpart (194 µg L-1) at pH 3.2. Experimental and theoretical analyses unveiled that coordinated sulfur actively modulates the electronic structure of the central Co atom, enhancing the adsorption and activation of PMS, thereby improving decontamination efficiency. Mechanistic studies further elucidate the predominant electron-transfer regime involved in oxidizing micropollutants by SNC@CoSA-0.05/PMS, with Co(IV)=O, •OH, and SO4•- being the auxiliary oxidizing species. This study not only offers a method for concurrent adjustment of active site density and electronic structure in ADMAs but also sheds light on the activation mechanisms of atomic metal sites.

The role of water and sodium ions in the activation of the µ-opioid receptor.

Dual effect of sodium ions: The activation of G-protein-coupled receptors depends on the presence of water molecules inside the receptor and also on allosteric interactions. The binding of sodium ions to the allosteric site of the µ opioid receptor was studied by microsecond molecular dynamics simulations and their seemingly contradictory roles in preventing ligand binding and facilitating receptor activation were explained.

Self-cementation of gold tailings activated by nonthermal plasma irradiated calcium (hydro)oxide.

The alkalinity of CaO is commonly insufficient in alkali-activating raw soils or minerals for the formation of cementation or geopolymerization. In this study, nonthermal plasma (NTP) irradiation was employed to activate traditional CaO to enhance its efficacy in alkali activation and further intensify the self-cementation of gold tailings. The solidification/stabilization (S/S) of the gold tailings-based matrix activated by NTP-CaO was better than that of CaO. The NTP irradiation enhanced the surface hydroxyl groups and oxygen atoms, decreased the binding energy, formed nanoparticles, and significantly changed the morphologies of the calcium activator. The dosage of the NTP-irradiated CaO (NTP-CaO) directly affected the self-cemented solidification/stabilization of gold tailings. The Johnson-Mehl-Avrami-Kolmogorov model was appropriate for analysing the NTP-CaO-activated geopolymerization kinetics of gold tailings. Three-dimensional (3D) structural minerals covered with small pores were determined in the NTP-CaO-activated cemented samples. The employment of NTP-CaO facilitated the formation of aluminosilicate geopolymers during the self-cementation of gold tailings according to comprehensive characterization strategies. The study achieves the efficient self-remediation of gold tailings by activating calcium precursors, which further solves the contradiction between salinization and alkali activation in the field of noncalcined cementitious materials.

New insights into MAIT cells in autoimmune diseases.

Mucosal-associated invariant T (MAIT) cells are resident T cells that express semi-invariant TCR chains and are restricted by monomorphic major histocompatibility complex (MHC) class I-related molecules (MR1). MAIT cells can be activated by microbial-specific metabolites (MR1-dependent mode) or cytokines (MR1-independent mode). Activated MAIT cells produce chemokines, cytotoxic molecules (granzyme B and perforin), and proinflammatory cytokines (IFN-γ, TNF-α, and IL-17), to clear pathogens and target infected cells involved in the pro-inflammatory, migratory, and cytolytic properties of MAIT cells. MAIT cells produce pro-inflammatory cytokines in the target organs of autoimmune diseases and contribute to the development and progression of autoimmune diseases. This article reviews the biological characteristics, activation mechanism, dynamic migration, and dual functions of MAIT cells, and focuses on the mechanism and potential application of MAIT cells in the early diagnosis, disease activity monitoring, and therapeutic targets of autoimmune diseases, to lay a foundation for future research.

Common and selective signal transduction mechanisms of GPCRs.

G protein-coupled receptors (GPCRs) are coupled by four major subfamilies of G proteins. GPCR coupling is processed through a combination of common and selective activation mechanisms together. Common mechanisms are shared for a group of receptors. Recently, researchers managed to identify shared activation pathways for the GPCRs belonging to the same subfamilies. On the other hand, selective mechanisms are responsible for the variations within activation mechanisms. Selective processes can regulate subfamily-specific interactions between the receptor and the G proteins, and intermediate receptor conformations are required to couple particular G proteins through G protein-specific activation mechanisms. Moreover, G proteins can also selectively interact with RGS (regulators of G protein signaling) proteins as well. Selective processes modulate the signaling profile of the receptor and the tissue they are present. This chapter summarizes the recent research conducted on common and selective signal transduction mechanisms within GPCRs from an evolutionary perspective.

Gravity-driven layered double hydroxide nanosheet membrane activated peroxymonosulfate system for micropollutant degradation.

For the first time in this study, CoAl-layered double hydroxide nanosheet membrane (LDHm) with abundant active sites was fabricated for peroxymonosulfate (PMS) activation with the mindset to catalytically degrade micropollutants. Depending on the catalyst loading, the developed LDHm can be driven under gravity at a permeate flux of approximately 80 L/m2 h and 210 L/m2 h at LDH loading of 0.80 mg/cm2 and 0.08 mg/cm2, respectively. Notably, the LDHm (0.63 mg) exhibited excellent PMS activation efficiency as indicated by 87.8% removal of the probe chemical (ranitidine) at 0.2 mM PMS, which was higher than that (37-44%) achieved by conventional LDH (5-20 mg)/PMS (0.2 mM) system. In addition to efficient degradation of several micropollutants, LDHm/PMS performance was not inhibited by variation in solution pH (4-8) as well as during long-term (29 h) continuous-flow operation. SO4•- and 1O2 were identified as the primary reactive species in the LDHm/PMS system, while both Co and Al participated in PMS activation. This study offers a simple strategy for efficient removal of several micropollutants with significantly reduced catalyst leaching, which could be applied sustainably in water treatment.

Ultrafast degradation of contaminants in a trace cobalt(II) activated peroxymonosulfate process triggered through borate: Indispensable role of intermediate complex.

Among all homogeneous catalysts, cobalt ions show the highest catalytic performance for the activation of peroxymonosulfate (PMS). Herein, we report a Co2+/PMS/H3BO3 system that can effectively generate reactive oxygen species (ROS) with ultra-low Co2+ dosage (5 µg/L). Co2+/PMS/H3BO3 system showed ultrafast reactivity and wide applicability for various pollutants. Sulfamethoxazole (SMX, 2 mg/L) could be completely removed within 5 min, and the corresponding kobs reached up to 1.1239 min-1. The introduction of H3BO3 significantly promoted the generation of ROS. The turnover frequency (TOF) calculated through dividing kobs by the cobalt ions concentration is as high as 224.78 min-1, which is much higher than most of the current research. Through a series of theoretical and experimental analyses, the complex of H2BO3--MS (HSO5B(OH)3-) was inferred to be the key substance that led to the excellent performance of the system. This work provides new insights into the Co2+/PMS system in the presence of borate buffer.

Recent advances in cobalt-activated sulfate radical-based advanced oxidation processes for water remediation: A review.

Sulfate radical-based advanced oxidation processes (SR-AOPs) have attracted increasing attention for the degradation of organic contaminants in water. The oxidants of SR-AOPs could be activated to generate different kinds of reactive oxygen species (ROS, e.g., hydroxyl radicals (OH), sulfate radicals (SO4-), singlet oxygen (1O2), and superoxide radicals (O2-)) by various catalysts. As one of the promising catalysts, cobalt-based catalysts have been extensively investigated in catalytic activity and stability during water remediation. This article mainly summarizes recent advances in preparation and applications of cobalt-based catalysts on peroxydisulfate (PDS)/peroxymonosulfate (PMS) activation since 2016. The review covers the development of homogeneous cobalt ions, cobalt oxides, supported cobalt composites, and cobalt-based mixed metal oxides for PDS/PMS activation, especially for the latest nanocomposites such as cobalt-based metal-organic frameworks and single-atom catalysts. This article also discussed the activation mechanisms and the influencing factors of different cobalt-based catalysts for activating PDS/PMS. Finally, the future perspectives on the challenges and applications of cobalt-based catalysts are presented at the end of this paper.

Growth Factor-Dependent and -Independent Activation of mTORC2.

The target of rapamycin complex 2 (TORC2) was discovered in 2002 in budding yeast. Its mammalian counterpart, mTORC2, was first described in 2004. Soon thereafter it was demonstrated that mTORC2 directly phosphorylates Akt on Ser473, ending a long search for the elusive 'second' insulin-responsive Akt kinase. In this review we discuss key evidence pertaining to the subcellular localization of mTORC2, highlighting a spatial heterogeneity that relates to mTORC2 activation. We summarize current models for how growth factors (GFs), such as insulin, trigger mTORC2 activation, and we provide a comprehensive discussion focusing on a new exciting frontier, the molecular mechanisms underpinning GF-independent activation of mTORC2.

Diverse effects of aqueous polar co-solvents on Candida antarctica lipase B.

Biocatalysis in mixtures of water and co-solvents represents an opportunity to expand the application of enzymes. However, in the presence of organic solvents, enzymes can undergo reversible inhibition, inactivation, or aggregation. In this work, we studied the effects of three co-solvents (methanol, acetone, and dimethyl sulfoxide - DMSO) on the function and structure of the recombinant Candida antarctica lipase B (rCALB), a widely used enzyme in biotechnological applications. The effects of co-solvents on rCALB were investigated by steady-state kinetics experiments, biophysical assays and by molecular dynamics simulations in the presence and upon incubation with the three co-solvents. Methanol and acetone were found to act as competitive inhibitors of rCALB and to promote its aggregation, whereas DMSO is a non-essential activator of rCALB.