Structural insights into auxin recognition and efflux by Arabidopsis PIN1.

Polar auxin transport is unique to plants and coordinates their growth and development1,2. The PIN-FORMED (PIN) auxin transporters exhibit highly asymmetrical localizations at the plasma membrane and drive polar auxin transport3,4; however, their structures and transport mechanisms remain largely unknown. Here, we report three inward-facing conformation structures of Arabidopsis thaliana PIN1: the apo state, bound to the natural auxin indole-3-acetic acid (IAA), and in complex with the polar auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). The transmembrane domain of PIN1 shares a conserved NhaA fold5. In the substrate-bound structure, IAA is coordinated by both hydrophobic stacking and hydrogen bonding. NPA competes with IAA for the same site at the intracellular pocket, but with a much higher affinity. These findings inform our understanding of the substrate recognition and transport mechanisms of PINs and set up a framework for future research on directional auxin transport, one of the most crucial processes underlying plant development.

A method for structure determination of GPCRs in various states.

G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by various ligands has been one of the primary goals in the field. Here we developed an effective universal method for GPCR cryo-electron microscopy structure determination without the need to prepare GPCR-signaling protein complexes. Using this method, we successfully solved the structures of the ß2-adrenergic receptor (ß2AR) bound to antagonistic and agonistic ligands and the adhesion GPCR ADGRL3 in the apo state. For ß2AR, an intermediate state stabilized by the partial agonist was captured. For ADGRL3, the structure revealed that inactive ADGRL3 adopts a compact fold and that large unusual conformational changes on both the extracellular and intracellular sides are required for activation of adhesion GPCRs. We anticipate that this method will open a new avenue for understanding GPCR structure‒function relationships and drug development.

Tissue distribution of metabolites in Cordyceps cicadae determined by DESI-MSI analysis.

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.

Effects of straw returning combined with blended controlled-release urea fertilizer on crop yields, greenhouse gas emissions, and net ecosystem economic benefits: A nine-year field trial.

Although straw returning combined with blended controlled-release urea fertilizer (BUFS) has been shown to improve wheat-maize rotation system productivity, their effects on greenhouse gas (GHG) emissions, carbon footprints (CF), and net ecosystem economic benefits (NEEB) are still unknown. Life cycle assessment was used to investigate a long-term (2013-2022) wheat-maize rotation experiment that included straw combined with two N fertilizer types [BUFS and (conventional urea fertilizer) CUFS] and straw-free treatments (BUF and CUF). The results showed that BUFS and CUFS treatments increased the annual yield by 13.8% and 11.5%, respectively, compared to BUF and CUF treatments. The BUFS treatment increased the yearly yield by 13.8% compared to the CUFS treatment. Since BUFS and CUFS treatments increased soil organic carbon (SOC) sink sequestration by 25.0% and 27.0% compared to BUF and CUF treatments, they reduced annual GHG emissions by 7.1% and 4.7% and CF per unit of yield (CFY) by 13.7% and 9.6%, respectively. BUFS treatment also increased SOC sink sequestration by 20.3%, reduced GHG emissions by 10.7% and CFY by 23.0% compared to CUFS treatment. It is worth noting that the BUFS and CUFS treatments increased the annual ecological costs by 41.6%, 26.9%, and health costs by 70.1% and 46.7% compared to the BUF and CUF treatments, but also increased the net yield benefits by 9.8%, 6.8%, and the soil nutrient cycling values by 29.2%, 27.3%, and finally improved the NEEB by 10.1%, 7.3%, respectively. Similar results were obtained for the BUFS treatment compared to the CUFS treatment, ultimately improving the NEEB by 23.1%. Based on assessing yield, GHG emissions, CF, and NEEB indicators, the BUFS treatment is recommended as an ideal agricultural fertilization model to promote sustainable and clean production in the wheat-maize rotation system and to protect the agroecological environment.

Photoactive and Intrinsically Fuel Sensing Metal-Organic Framework Motors for Tailoring Collective Behaviors of Active-Passive Colloids.

Microorganisms display nonequilibrium predator-prey behaviors, such as chasing-escaping and schooling via chemotactic interactions. Even though artificial systems have revealed such biomimetic behaviors, switching between them by control over chemotactic interactions is rare. Here, a spindle-like iron-based metal-organic framework (MOF) colloidal motor which self-propels in glucose and H2 O2 , triggered by UV light is reported. These motors display intrinsic UV light-triggered fuel-dependent chemotactic interactions, which are used to tailor the collective dynamics of active-passive colloidal mixtures. In particular, the mixtures of active MOF motors with passive colloids exhibit distinctive "chasing-escaping" or "schooling" behaviors, depending on glucose or hydrogen peroxide being used as the fuel. The transition in the collective behaviors is attributed to an alteration in the sign of ionic diffusiophoretic interactions, resulting from a change in the ionic clouds produced. This study offers a new strategy on tuning the communication between active and passive colloids, which holds substantial potentials for fundamental research in active matter and practical applications in cargo delivery, chemical sensing, and particle segregation.

Cell-Mimic Directional Cargo Transportation in a Visible-Light-Activated Colloidal Motor/Lipid Tube System.

Active tether and transportation of cargoes on cytoskeletal highway enabled by molecular motors is key for accurate delivery of vesicles and organelles in the complex intracellular environment. Here, a hybrid system composed of colloidal motors and self-assembled lipid tubes is designed to mimic the subcellular traffic system in living cells. The colloidal motors, composed of gold-coated hematite, display light-activated self-propulsion tunable by the light intensity and the concentration of hydrogen peroxide fuel. Importantly, the motors show light-switchable binding with lipid cargoes and attachment to the lipid tubes, whereby the latter act as the motor highways. Upon assembly, the colloidal motor/lipid tube system demonstrates directional delivery of lipid vesicles, emulating intracellular transportation. The assembly and function of the hybrid system are rationalized by a cooperative action of light-triggered electrophoretic and hydrodynamic effects, supported by finite element analysis. A synthetic analog of the biological protein motor/cytoskeletal filament system is realized for the manipulation and delivery of different matter at the microscale, which is expected to be a promising platform for various applications in materials science, nanotechnology, microfluidics, and synthetic biology.

Structure of the platelet glycoprotein Ib receptor in complex with a novel antithrombotic agent.

Agkisacucetin, a snake C-type lectin-like protein isolated from the venom of Deinagkistrodon acutus (formerly Agkistrodon acutus), is a novel antithrombotic drug candidate in phase 2 clinical trials. Agkisacucetin specifically recognizes the platelet surface receptor glycoprotein Ib α chain (GPIbα) to block GPIb and von Willebrand factor (VWF). In this study, we solved the crystal structure of the GPIbα N-terminal domain (residues 1-305) in complex with agkisacucetin to understand their molecular recognition mechanism. The crystal structure showed that agkisacucetin primarily contacts GPIbα at the C-terminal part of the conserved leucine-rich repeat (LRR) domain (LRR-6 to LRR-8) and the previously described "ß-switch" region through the ß chain. In addition, we found that agkisacucetin α chain contacts part of the GPIbα C-terminal peptide after the LRR domain through complementary charge interactions. This C-terminal peptide plays a key role in GPIbα and thrombin recognition. Therefore, our structure revealed that agkisacucetin can sterically block the interaction between the GPIb receptor and VWF and thrombin proteins to inhibit platelet function. Our structural work provides key molecular insights into how an antithrombotic drug candidate recognizes the GPIb receptor to modulate platelet function to inhibit thrombosis.

Active self-assembly of colloidal machines with passive rotational parts via coordination of phoresis and osmosis.

The organization of microscopic objects into specific structures with movable parts is a prerequisite for building sophisticated micromachines with complex functions, as exemplified by their macroscopic counterparts. Here we report the self-assembly of active and passive colloids into micromachinery with passive rotational parts. Depending on the attachment of the active colloid to a substrate, which varies the degrees of free freedom of the assembly, colloidal machines with rich internal rotational dynamics are realized. Energetic analysis reveals that the energy efficiency increases with the degrees of freedom of the machine. The experimental results can be rationalized by the cooperation of phoretic interaction and osmotic flow encoded in the shape of the active colloid, which site-specifically binds and exerts a torque to passive colloids, supported by finite element calculations and mesoscale simulations. Our work offers a new design principle that utilizes nonequilibrium interfacial phenomena for spontaneous construction of multiple-component reconfigurable micromachinery.

Mechanism of action of quercetin in rheumatoid arthritis models: meta-analysis and systematic review of animal studies.

Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, dose selection and the improvement of quercetin's bioavailability remain to be explored.

Inorganic-Organic Hybrid Copolymeric Colloids as Multicolor Emission, Fuel-Free, UV- and Visible-Light-Actuated Micropumps.

Light-actuated micromachines are of enormous interest due to their ability to harvest light for triggering catalytic reactions to acquire free energy for mechanical work. This work presents an inorganic-organic hybrid copolymeric poly(cyclotriphosphazene-co-barbituric acid) colloid, which displays multiwavelength excited emission and catalytic activities, exploiting the unique structural, chemical, and optical features of inorganic heterocyclic ring hexachlorocyclotriphosphazene and organic co-monomer barbituric acid. Specifically, this work reveals particle-resolved unusual multicolor emission under excitation with the same or different wavelengths of light using fluorescence microscopy. The result is rationalized by density functional theory studies. In this work, the authors find that emission is coincident with fluorometric measurements, and the photocatalytic properties are anticipated from the overall band structure. This work also demonstrates the use of these colloids as micropumps, which can be remotely activated by UV, blue, and green lights under fuel-free conditions, and ascribe the behavior to ionic diffusiophoresis arising from light-triggered generation of H+ and other charged species. This work offers a new class of polymeric colloids with multiple-wavelength excited emission and catalytic activities, which is expected to open new opportunities in the design of fuel-free, photo-actuated micromachines and active systems.

WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the function of p53 in suppressing metastasis.

Accumulating evidence suggests that p53 plays a suppressive role in cancer metastasis, yet the underlying mechanism remains largely unclear. Regulation of actin dynamics is essential for the control of cell migration, which is an important step in metastasis. The Arp2/3 complex is a major nucleation factor to initiate branched actin polymerization that drives cell migration. However, it is unknown whether p53 could suppress metastasis through modulating Arp2/3 function. Here, we report that WDR63 is transcriptionally upregulated by p53. We show with migration assays and mouse xenograft models that WDR63 negatively regulates cell migration, invasion, and metastasis downstream of p53. Mechanistically, WDR63 interacts with the Arp2/3 complex and inhibits Arp2/3-mediated actin polymerization. Furthermore, WDR63 overexpression is sufficient to dampen the increase in cell migration, invasion, and metastasis induced by p53 depletion. Together, these findings suggest that WDR63 is an important player in the regulation of Arp2/3 function and also implicate WDR63 as a critical mediator of p53 in suppressing metastasis.

Reply to the 'Comment on "Can bulk nanobubbles be stabilized by electrostatic interaction?"' by S. Koshoridze and Y. Levin, Phys. Chem. Chem. Phys., 2022, 24, DOI: 10.1039/D1CP04406K.

We investigated the effect of the adsorbed ions on the stability of nanobubbles suspended in the liquid in a recent article published in Physical Chemistry Chemical Physics. We calculated the electrostatic pressure using the classical electrical double layer (EDL) theory and pointed out that the electrostatic pressure is overestimated in previous theories due to the overlook of the stress in the diffusive double layer. Recently, S. I. Koshoridze and Yu. K. Levin questioned our calculations and results based on their intuition that diffusive ions in the EDL will drift and, therefore, not contribute to hydrostatic pressure. In this reply, we explain why mobile ions can also produce hydrostatic pressure from a hydrodynamic perspective.

A Low-Latency RDP-CORDIC Algorithm for Real-Time Signal Processing of Edge Computing Devices in Smart Grid Cyber-Physical Systems.

Smart grids are being expanded in scale with the increasing complexity of the equipment. Edge computing is gradually replacing conventional cloud computing due to its low latency, low power consumption, and high reliability. The CORDIC algorithm has the characteristics of high-speed real-time processing and is very suitable for hardware accelerators in edge computing devices. The iterative calculation method of the CORDIC algorithm yet leads to problems such as complex structure and high consumption of hardware resource. In this paper, we propose an RDP-CORDIC algorithm which pre-computes all micro-rotation directions and transforms the conventional single-stage iterative structure into a three-stage and multi-stage combined iterative structure, thereby enabling it to solve the problems of the conventional CORDIC algorithm with many iterations and high consumption. An accuracy compensation algorithm for the direction prediction constant is also proposed to solve the problem of high ROM consumption in the high precision implementation of the RDP-CORDIC algorithm. The experimental results showed that the RDP-CORDIC algorithm had faster computation speed and lower resource consumption with higher guaranteed accuracy than other CORDIC algorithms. Therefore, the RDP-CORDIC algorithm proposed in this paper may effectively increase computation performance while reducing the power and resource consumption of edge computing devices in smart grid systems.

Effect of Wuzi Yanzong prescription on oligoasthenozoospermia rats based on UPLC-Q-TOF-MS metabolomics.

CONTEXT: Wuzi Yanzong Prescription (WYP) has long been used to treat male infertility, with convincing clinical evidence. However, its mechanism of action is not clear. OBJECTIVE: WYP chemical components were quantified by HPLC, and the effect on oligoasthenozoospermia rats was explored based on UPLC-Q-TOF-MS metabonomics technology. MATERIALS AND METHODS: The solution was extracted by alcohol and water; the content of eight components in the extracting solution was determined by HPLC. Twenty-four Sprague-Dawley rats were randomly divided into control (CG), model (MG) and administration (PG) groups. Oligoasthenozoospermia was induced for 30 days in all, but the CG with daily oral doses of 20 mg/kg Tripterysium glycosides (TG). PG was given daily oral doses of WYP solution (1.08 g/kg), CG and MG received the same volume of distilled water, all administered for 30 days. After the last administration, the serum samples were collected and detected by UPLC-Q-TOF-MS. RESULTS: An HPLC method for simultaneous determination of chlorogenic acid (0.081%), ellagic acid (0.021%), hyperoside (0.032%), verbascoside (0.011%), isoquercitrin (0.041%), astragalin (0.026%), kaempferol (0.009%) and schisandrin (0.014%) was established. Moreover, the 74 potential biomarkers and eight metabolic pathways related to oligoasthenozoospermia were identified by multivariate analysis and metabolite profiling. WYP can regulate 36 markers, mainly involving amino acid metabolism, lipid metabolism and nucleotide metabolism. DISCUSSION AND CONCLUSIONS: This is a simple and accurate method for quality control of WYP. It further enriches the potential mechanism of WYP in the treatment of oligoasthenozoospermia. It can provide a theoretical basis for the rational application of WYP.

Ionic Effects in Ionic Diffusiophoresis in Chemically Driven Active Colloids.

We study experimentally the effect of added salt in the phoretic motion of chemically driven colloidal particles. We show that the response of passive colloids to a fixed active colloid, be it attractive or repulsive, depends on the ionic strength, the ζ potential, and the size of the passive colloids. We further report that the direction of self-propulsion of Janus colloids can be reversed by decreasing their ζ potential below a critical value. By constructing an effective model that treats the colloid and ions as a whole subjected to the concentration field of generated ions and takes into account the joint effect of both generated and background ions in determining the Debye length, we demonstrate that the response of the passive colloids and the velocity of the Janus colloids can be quantitatively captured by this model under the ionic diffusiophoresis theory beyond the infinitely-thin-double-layer limit.

Magnetic Manipulation and Assembly of Nonmagnetic Colloidal Rods in a Ferrofluid.

We investigated experimentally and theoretically the interactions and assembly of rodlike colloids in a ferrofluid confined at solid/liquid interface by the gravity under external magnetic fields. We first derived analytical expressions for the interaction energy of a single rod with the external magnetic field and the interaction between two rods using classical electromagnetism. The theory well captured the experimentally observed alignment of a single rod along the field direction under an in-plane field and switching between the horizontal and the vertical configurations in an out-of-plane field due to the competition between the magnetic energy and the gravitational energy. The theory can also predict the symmetric position fluctuations of a free rod on a fixed one at 90° and the gradual bias toward the end of the fixed rod as the angle was reduced to 0°, favoring the tip-toe arrangement. Finally, we showed that this anisotropic interaction led to the formation of chain-like structures, whose growth kinetics followed a simple scaling behavior with time. This work provides a theoretical framework for understanding the behaviors of rodlike colloids in ferrofluids and highlights the importance of shape anisotropy in manipulating colloids and their self-assembly.

Collective Dynamics of Bulk Nanobubbles with Size-Dependent Surface Tension.

It has been suggested that irreversible adsorption at the gas/liquid interface of bulk nanobubbles will reduce the Laplace pressure, leading to their stability. However, most previous studies have focused on the stability of individual nanobubbles. Bulk nanobubbles are polydispersed suspensions, and gas molecules can diffuse between bubbles, leading to their collective dynamics, which may be crucial to understanding their formation process and stability. In this study, we proposed a mean-field theory for computing the evolution of the size-distribution function of bulk nanobubbles with size-dependent surface tension. We applied this theory to investigate the evolution of bulk nanobubbles with insoluble surfactants pinned at their gas/water interface. The results show that Ostwald ripening can be suppressed when enough surfactants are adsorbed. Bulk nanobubbles can be produced by the shrinkage of microbubbles in an air-saturated solution. The mean stable size is controlled by the amount of surfactants and the initial microbubble concentration; these predictions are qualitatively consistent with the experimental results of micro/nanobubbles produced using the microfluidic method.

Can bulk nanobubbles be stabilized by electrostatic interaction?

It has been suggested that electrostatic stress arising from charges accumulated at the surface of nanobubbles might balance Laplace pressure leading to their stability. This mechanism has been widely discussed in the nanobubble field for the past decade. However, the stress in the diffusive double layer was overlooked when calculating the electrostatic effect in previous theories. In this communication, we recalculated this effect using the classical double layer theory. Combined with experimentally measured zeta potential, we find that the ratio of electrostatic pressure to Laplace pressure is much less than 10-2, which suggests that electrostatic interaction may not be the main factor for stabilizing bulk nanobubbles.

Guizhi-Shaoyao-Zhimu decoction attenuates bone erosion in rats that have collagen-induced arthritis via modulating NF-κB signalling to suppress osteoclastogenesis.

CONTEXT: Guizhi-Shaoyao-Zhimu decoction (GSZD) is commonly used to treat rheumatoid arthritis (RA), but its mechanism is unclear. OBJECTIVE: To investigate the effect of GSZD on bone erosion in type II collagen (CII)-induced arthritis (CIA) in rats and to identify the underlying mechanism. MATERIALS AND METHODS: The CIA model was prepared in male Wistar rats by two subcutaneous injections of CII, 1 mg/mL. Fifty CIA rats were randomized equally into the control group given saline daily, the positive group given saline daily and methotrexate 0.75 mg/kg once a week, and three GSZD-treated groups gavaged daily with 800, 1600 and 3200 mg/kg of GSZD for 21 days. GSZD effects were assessed by paw volume, arthritic severity index and histopathology. Cytokine levels were determined by ELISA. The effects of GSZD on RAW264.7 cells were evaluated by receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption assay. Expression of IκB-α and p65 was measured by Western blotting. Major components of GSZD were identified by HPLC. RESULTS: Arthritis index score, paw volume and bone destruction score showed that GSZD improved inflammatory symptoms and reduced joint tissue erosion (p < 0.01). GSZD decreased RANKL, and the number of osteoclasts (OCs) in joint tissues (p < 0.01) and increased osteoprotegerin levels (p < 0.01). GSZD inhibited RANKL-induced RAW264.7 differentiation and reduced bone resorption by OCs. GSZD upregulated IκB (p < 0.01) and p65 (p < 0.01) in the cytoplasm and downregulated p65 (p < 0.01) in the cell nucleus. CONCLUSIONS: Guizhi-Shaoyao-Zhimu decoction has an anti-RA effect, suggesting its possible use as a supplement and alternative drug therapy for RA.

Research progress on inflammatory mechanism of primary Sjögren syndrome.

Primary Sjögren syndrome is an autoimmune disease, in which a large number of lymphocytes infiltrate the exocrine glands and cause gland dysfunction. Its pathogenesis is related to the chronic inflammation of the exocrine glands caused by genetic factors, immunodeficiency or viral infection. Long-term inflammation leads to accelerated apoptosis of epithelial cells, disordered gland structure, increased expression of proinflammatory cytokine such as CXC subfamily ligand (CXCL) 12, CXCL13, B cell-activating factor (BAF), interleukin (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α in submandibular gland. With the action of antigen-presenting cells such as dendritic cells and macrophages, lymphocytes (mainly B cells) are induced to mature in secondary lymphoid organs and migrate to the submandibular gland to promotes the formation of germinal centers and the synthesis of autoantibodies. Meanwhile, innate lymphocytes, vascular endothelial cells and mucosa-associated constant T cells as important immune cells, also participated in the inflammatory response of the submandibular gland in primary Sjögren syndrome through different mechanisms. This process involves the activation of multiple signal pathways such as JAK/STAT, MAPK/ERK, PI3K/AKT/mTOR, PD-1/PD-L1, TLR/MyD88/NF-κB, BAF/BAF-R and IFN. These signaling pathways interact with each other and are intricately complex, causing lymphocytes to continuously activate and invade the submandibular glands. This article reviews the latest literature to clarify the mechanism of submandibular gland inflammation in primary Sjögren syndrome, and to provide insights for further research.