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.

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.

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.

Realignment Surgery for Malunited Ankle Fracture.

OBJECTIVE: To investigate the characteristics and the results of realignment surgery for the treatment of malunited ankle fracture. METHODS: Thirty-three patients with malunited fractures of the ankle who underwent reconstructive surgery at our hospital from January 2010 to January 2014 were reviewed. The tibial anterior surface angle (TAS), the tibiotalar tilt angle (TTA), the malleolar angle (MA), and the tibial lateral surface angle (TLS) were measured. Clinical assessment was performed with use of the American Orthopaedic Foot and Ankle Society (AOFAS) scale and visual analogue scale (VAS) scores, and the osteoarthritis stage was determined radiographically with the modified Takakura classification system. The Wilcoxon matched-pairs test was used to analyze the difference between the preoperative and the postoperative data. RESULTS: The mean follow-up was 36 months (range, 20-60 months). The mean age at the time of realignment surgery was 37.1 years (range, 18-62 years). Compared with preoperation, the TAS at the last follow-up showed a significant increase (88.50° ± 4.47° vs. 90.80° ± 3.49°, P = 0.0035); similar results were observed in TTA (1.62° ± 1.66° vs. 0.83° ± 0.90°, P < 0.01) and MA (82.30° ± 8.03° vs. 78.70° ± 4.76°, P = 0.005). At the last follow-up, the mean AOFAS score was significantly increased compared with the score at preoperation (44.5 ± 13.7 vs. 78.0 ± 8.9, P < 0.01). Significant differences in VAS scores were found at the last follow-up (6.76 ± 1.03 vs. 2.03 ± 1.21, P < 0.01). There was no significant difference in the Takakura grade between the preoperation and the last follow-up. One patient had increased talar tilt postsurgery; the postoperative talar tilt angle of this patient was 20°. One patient had progressive ankle osteoarthritis, and was treated by ankle joint distraction. CONCLUSIONS: Realignment surgery for a malunited ankle fracture can reduce pain, improve function, and delay ankle arthrodesis or total ankle replacement. Postoperative large talar tilt and advanced stages of ankle arthritis are the risk factors for the surgery.

Enantioselective and solvent-controlled diastereoselective Mannich reaction of isatin imines with hydroxyacetone: synthesis of 3-substituted 3-aminooxindoles.

The diastereoselectively switchable enantioselective Mannich reaction of isatin imines with hydroxyacetone is reported. The chiral primary amino acid catalyzed this Mannich reaction to afford both anti- and syn-Mannich adducts in high yields, good diastereoselectivities, and enantioselectivities. The reason for the solvent control of the diastereoselectivity phenomenon was investigated.