Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Protective effect of carbon dots as antioxidants on intestinal inflammation by regulating oxidative stress and gut microbiota in nematodes and mouse models.

Inflammatory bowel disease (IBD) is a recurrent chronic colitis disease with increasing incidence and prevalence year by year. The single efficacy and significant side effects of traditional IBD treatment drugs have promoted the flourishing development of new drugs. Inspired by many health benefits of carbon dots (CDs) based nanomedicine in biomedical applications, a metal-free carbon dots (CP-CDs) was synthesized from citric acid and polyethylene polyamine to treat colitis. Oxidative stress tests at the cellular and nematode levels demonstrated CP-CDs have good antioxidant effects, while the toxicity of CP-CDs to cells and nematodes is low. CP-CDs were further applied to dextran sodium sulfate (DSS)-induced colitis in mice models, and it was found that CP-CDs can reduce the disease activity index (DAI) score of colon tissue and restore the intestinal barrier. Further, the anti-colitis mechanisms of CP-CDs were explored, one of which is to regulate intestinal oxidative stress in inflammatory mice, further reducing the expression of inflammatory cytokines, and thus alleviating colitis. Notably, 16S rRNA sequence analysis showed that the abundance of beneficial bacteria (Ligilactobacillus and Enterorhabdus) in the intestinal tract increased, while that of harmful bacteria (unclassified_Clostridia_UCG_014) decreased after CP-CDs treatment, indicating that CP-CDs rebalancing the gut microbiota destroyed by DSS is another important mechanism. In short, these non-toxic carbon dots not only have the potential for multi-factor combined relief of colitis but also offer an alternative therapy medicine for patients suffering from IBD.

Dual-emission carbon dots for ratiometric fluorescence sensing of thiabendazole in fruits.

Quantitative determination of pesticides in fruits and vegetables is essential for human healths. Herein, a new dual-emission carbon dots with high fluorescence stability at a pH range of 4-10 and a temperature range of 0-60 °C was synthesized. And a novel ratiometric fluorescence probe was proposed to detect thiabendazole (TBZ) residue with a wide linear range (0-1000 µM) and low detection limit (0.15 µM). The emission at 512 nm exhibited a special "turn-off" fluorescence sensing of TBZ due to internal filter effect, while that at 361 nm barely changed and worked as reference. Furthermore, the ratiometric fluorescence strategy was successfully applied for determining TBZ in fruits with good recoveries (96.73%-111.17 %, 93.29%-120.78 % and 96.28%-100.57 %, respectively). Notably, the constructed ratiometric fluorescence probe had comparable accuracy to HPLC in detecting unknown concentrations of TBZ in pear juice, demonstrating dual-emission carbon dots possess wide and promising applicability for fluorescence sensing pesticides in the future.

Simulating immunosuppressive mechanism of Microplitis bicoloratus bracovirus coordinately fights Spodoptera frugiperda.

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.

Synthesis, properties and mechanism of carbon dots-based nano-antibacterial materials.

Antibiotics play an important role in the treatment of diseases, but bacterial resistance caused by their widespread and unreasonable use has become an urgent problem in clinical treatment. With the rapid advancement of nanoscience and nanotechnology, the development of nanomedicine has been transformed into a new approach to the problem of bacterial resistance. As a new type of carbon-based nanomaterial, carbon dots (CDs) have attracted the interest of antibacterial researchers due to their ease of preparation, amphiphilicity, facile surface functionalization, and excellent optical properties, among other properties. This article reviewed the synthesis methods and properties of various CDs and their composites in order to highlight the advancements in the field of CDs-based antibacterial agents. Then we focused on the relationship between the principal properties of CDs and the antibacterial mechanism, including the following: (1) the physical damage caused by the small size, amphiphilicity, and surface charge of CDs. (2) Photogenerated electron transfer characteristics of CDs that produce reactive oxygen species (ROS) in themselves or in other compounds. The ability of ROS to oxidize can lead to the lipid peroxidation of cell membranes, as well as damage proteins and DNA. (3) The nano-enzyme properties of CDs can catalyze reactions that generate ROS. (4) Synergistic antibacterial effect of CDs and antibiotics or other nanocomposites. Finally, we look forward to the challenges that CDs-based nanocomposites face in practical antibacterial applications and propose corresponding solutions to further expand the application potential of nanomaterials in the treatment of infectious diseases, particularly drug-resistant bacterial infections.

NAP1L1 is a novel microtubule-associated protein.

Microtubule-associated proteins (MAPs) regulate assembly and stability of microtubules (MTs) during cell cytokinesis, cell migration, neuronal growth, axon guidance, and synapse formation. Using data mining of the Human Protein Atlas database and experimental screening, we identified nucleosome assembly protein 1 like 1 (NAP1L1) as a new MAP. The Human Protein Atlas and PubMed database screening identified 99 potential new MAPs. Twenty candidate proteins that highly co-localized with MTs were exogenously expressed with green fluorescent protein (GFP) or hemagglutinin (HA) tags in tissue culture cells and MTs were co-stained for immunofluorescent microscopy. We found that NAP1L1 is mainly localized in the cytosol with MTs during interphase. Using bacterially expressed recombinant NAP1L1 fragments and purified MTs, we biochemically mapped the MT-binding site on the N-terminal region (1-72aa) and the central region (164-269aa) of NAP1L1. NAP1L1 dimerizes through the long helix region (73-163aa), and full-length NAP1L1 induces the formation of thick MTs, indicating that NAP1L1 has the ability to bundle MTs in cells. Analysis of publicly available RNA-seq data of NAP1L1 depleted cells suggested that NAP1L1 is involved in cell adhesion and migration in agreement with the function of NAP1L1 as a MAP.

Microtubule-associated proteins and enzymes modifying tubulin.

Microtubules (MTs) are essential for many cellular processes including establishment of cell shape and polarity, chromosome segregation, vesicle transport, and nuclear positioning. Human cells express 22 tubulin isoforms that have both overlapping and distinctive functions. Tubulins reversely polymerize to form cylindrical MTs, while MT-associated proteins (MAPs), posttranslational modifications (PTMs), and mechanical forces regulate their functions. To help both tubulin researchers and medicinal chemists, this review article lists 489 MAPs, 43 known enzymes that mediate PTMs, and 306 drugs that influence the functions of MTs and MAPs and discusses recent microtubule research. Readers are able to sort the list based on name, size, functions, related human diseases, and date of discovery. The list also contains links to Uniprot and Protein Atlas databases to access further details such as protein structure, associated proteins, subcellular localization, expression levels in cells and tissues, mutations, and pathology. Because the microtubule cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target on MT and MAPs hold potential to treat these diseases and are also listed.

Bracovirus Sneaks Into Apoptotic Bodies Transmitting Immunosuppressive Signaling Driven by Integration-Mediated eIF5A Hypusination.

A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression.