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Summary: 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.

Oomycete, particularly Phytophthora species, causes the most devastating crop diseases, such as potato late blight, and threatens the sustainable crop production worldwide. Our previous studies identified Resistance to Phytophthora parasitica 1 (RTP1) as a negative regulator of Arabidopsis resistance to multiple biotrophic pathogens and RTP1 loss-of-function plants displayed rapid cell death and reactive oxygen species (ROS) production during early colonization of P. parasitica. In this study, we aim to decipher the mechanism of RTP1-mediated cell death, and identify a member of vaculoar processing enzymes (VPEs), γVPE, playing a role in rtp1-mediated resistance to P. parasitica and cell death occurrence. Our results showed up-regulation of the expression of γVPE as well as increased VPE/caspase 1-like protease activity in P. parasitica-infected rtp1 mutant plants. Besides, we found that the VPE/caspase 1-like protease activity was required for the cell death occurrence in Arabidopsis plants during the infection of P. parasitica as well as rtp1-mediated resistance to P. parasitica. Further pathogenicity assays on either Arabidopsis γvpe mutant plants or leaves of Nicotiana benthamiana with transient overexpression of γVPE demonstrated γVPE could positively affect plant resistance to P. parasitica. Together, our studies suggest that γVPE might function as an important regulator of plant defense and cell death occurrence in response to P. parasitica infection, and VPE/caspase 1-like protease activity is required for rtp1-mediated resistance to P. parasitica.

This study aims to investigate the impacts of the spring sensible heat (SH) over the Tibetan Plateau (TP) and the El Niño–Southern Oscillation (ENSO) in the preceding wintertime on midsummer (July–August) precipitation over South China under the different Pacific decadal oscillation (PDO) phases. More specifically, eight classifications are adopted at the demarcation point around 1996 when the spring SH over the TP and the midsummer precipitation in South China occurred as well as the PDO phase transition, including positive and negative SHs and ENSOs under a positive PDO phase (1979–1996) and a negative PDO phase (1997–2019), respectively, based on the Niño-3 index and the spring SH calculated from 48 stations over the central and eastern parts of the TP. The results show that both the spring SH and the ENSO in preceding wintertime have a significant impact on the midsummer precipitation over South China; that is, when the two factors are in their respective positive (negative) phase, the midsummer precipitation in South China is generally less (more). Importantly, the phase change of background field PDO can significantly enhance the effect of the SH and the ENSO on summer precipitation over South China. Moreover, compared with the preceding wintertime ENSO, the spring SH over the TP contributes more to the midsummer precipitation in South China based on analyses of their independent and synergistic effects. The main mechanism responsible for the anomalous midsummer precipitation over South China are the combined effects of the South Asian high (SAH) and the western Pacific subtropical high (WPSH), which are controlled by the spring SH anomaly over the TP and the ENSO, respectively. Deep understanding of the dominant factors of the midsummer precipitation over South China will help understand the local climate change and reduce the losses caused by drought and flood disasters.

Objective To evaluate the effect of pitavastatin on high-density lipoprotein cholesterol (HDL-C) level and cholesterol efflux and antioxidative properties of HDL in patients with dyslipidemia and stable coronary disease. Methods The study population included 60 patients with stable coronary disease and dyslipidemia. They were randomly allocated to treatment by pitavastatin 2-4 mg per day or atorvastatin 10-20 mg per day and followed up for six months. The cholesterol efflux and activities of antioxidative enzymes paraoxonase-1 (PON-1) were evaluated before and after statins treatment. Results The effect of the 6-month treatment with pitavastatin on serum HDL-C level was significantly greater than that of atorvastatin (% change: pitavastatin 9.0% vs atorvastatin 1.8%, P＜0.01). HDL induced cholesterol efflux increased significantly after the 6- month treatment with pitavastatin while it not was affected by atorvastatin treatment. However, HDL-associated PON-1 in both pitavastatin group and atovastatin group all increased. The activity of PON-1 increased by 21% with pitavastatin and 24% with atorvastatin, while the activity of arylesterase increased by 18% with pitavastatin and 17% with atorvastatin (P＜0.001). Conclusions Pitavastatin elevates the HDL-C level, enhances the cholesterol efflux and antioxidative effect of HDL. Therefore, pitavastatin increases the amount of functional HDL without attenuating HDL quality.

Glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) and overexpression of the EPSPS gene is one of the molecular mechanisms conferring glyphosate resistance in weeds. A regulatory sequence of EPSPS gene was isolated previously, and an alteration in its 5´-untranslated region (UTR) pyrimidine (Py)-rich stretch element is involved in the regulation of EPSPS expression in glyphosate-resistant (GR) Eleusine indica. However, the transcription factors involved in this regulatory sequence remain to be elucidated. In this study, we investigated the regulatory network of EPSPS overexpression associated genes in a GR E. indica population by RNA-seq. The differentially expressed transcript analyses revealed that glyphosate treatment caused an increase in the expression of 2752 unigenes and a decrease in the expression of 4025 unigenes in the GR E. indica, compared to the glyphosate-susceptible (GS) E. indica. Among them, 1373 unigenes were identified to be co-expressed with the EPSPS gene in GR E. indica. GO and KEGG pathway analyses showed that the up-regulated unigenes were mainly enriched in chloroplasts and associated with the shikimate biosynthesis pathway, chlorophy II and peroxisome metabolism processes. Notably, the expression of a Shikimate kinase which catalyzed the conversion of Shikimate to Shikimate 3-phosphate (S3P, a substrate of EPSPS), was also up-regulated. Eight transcription factors were identified as likely to be involved in the regulation of the EPSPS expression, and three of them (ARF2, ARF8 and BPC6) showed more binding sites because of a (CT)n insertion of the 5´-UTR Py-rich stretch element in GR. However, the yeast one-hybrid assay illustrated that ARF8 and BPC6 could bind to the 5´-UTR Py-rich stretch element of wild type EPSPS, but could not bind to the mutated form. Our data suggests that the transcriptional regulation of EPSPS expression is complex and was significantly altered in GR E. indica. These discoveries provide new references for further study of the EPSPS overexpression mechanism that endows glyphosate resistance.

Objective To investigate the outcomes of total knee arthroplasty (TKA) in patients with a prior femoral or tibial fracture, and identify the risk factors for surgical site complications and reoperations. Methods Seventy‐one TKAs performed in 71 patients with a prior tibial or femoral fracture between January 2005 and December 2016 were reviewed retrospectively. Forty males (40 knees) and 31 females (31 knees) were included. The mean age at the time of TKA was 59.2 (range, 29–83) years. Outcomes were assessed using the Knee Society score before surgery and at the final follow‐up visit. The patients' satisfaction rates were evaluated. Complications and reoperations were recorded by clinical and radiographic assessment. Logistic regression analysis was used to identify the risk factors for surgical site complications and reoperations. Results The median follow‐up period was 4.7 (range, 3.2–7.1) years. The median knee range of motion increased from 90° preoperatively to 110° at the latest follow‐up. The Knee Society knee score and function score improved from 35 (30, 40) and 40 (30, 50) to 90 (82, 93) and 90 (65, 100), respectively. The degree of overall satisfaction after TKA surgery was very satisfied in 41 patients, satisfied in 20 patients, neutral in four patients, dissatisfied in four patients, and very dissatisfied in two patients. The overall satisfaction (very satisfied and satisfied) rate was 85.9% (61 knees). Twelve knees (16.9%) had 19 surgical site complications. Six knees (8.3%) underwent reoperations, including one revision due to periprosthetic joint infection, one debridement and implant retention for superficial infection, two debridements for delayed wound healing, one open reduction and internal fixation for supracondylar fracture, and one re‐fixation and bone grafting for hardware failure after a combined femoral shaft osteotomy and TKA. Preoperative patella baja was diagnosed in 12 knees, and was identified as a risk factor for surgical site complications and reoperations. Conclusions TKA for post‐fracture osteoarthritis significantly relieved pain and improved function, but the incidence of surgical site complications and reoperations was high. Preoperative patella baja was a risk factor for surgical site complications and reoperations.

Introduction: Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998– 2008 require reassessment in light of changes in the current treatment landscape. Aim and methods: PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses). Results: Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR−) of 0.63 (95% confidence interval [CI], 0.43– 0.94; P=0.020) and 1.76 (95% CI, 0.97– 3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2– 12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24– 26.30), which shrunk to 2.03 (95% CI, 1.30– 9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses. Conclusion: These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings. [ABSTRACT FROM AUTHOR]