Heat Shock Transcription Factor CgHSF1 Is Required for Melanin Biosynthesis, Appressorium Formation, and Pathogenicity in <i>Colletotrichum gloeosporioides</i>

Heat shock transcription factors (HSFs) are a family of transcription regulators. Although HSFs’ functions in controlling the transcription of the molecular chaperone heat shock proteins and resistance to stresses are well established, their effects on the pathogenicity of plant pathogenic fungi remain unknown. In this study, we analyze the role of CgHSF1 in the pathogenicity of Colletotrichum gloeosporioides and investigate the underlying mechanism. Failure to generate the Cghsf1 knock-out mutant suggested that the gene is essential for the viability of the fungus. Then, genetic depletion of the Cghsf1 was achieved by inserting the repressive promoter of nitrite reductase gene (PniiA) before its coding sequence. The mutant showed significantly decrease in the pathogenicity repression of appressorium formation, and severe defects in melanin biosynthesis. Moreover, four melanin synthetic genes were identified as direct targets of CgHSF1. Taken together, this work highlights the role of CgHSF1 in fungal pathogenicity via the transcriptional activation of melanin biosynthesis. Our study extends the understanding of fungal HSF1 proteins, especially their involvement in pathogenicity

Predicting the Impact of Climate Change on the Distribution of a Neglected Arboviruses Vector (Armigeres&nbsp;subalbatus) in China

The geographic boundaries of arboviruses continue to expand, posing a major health threat to millions of people around the world. This expansion is related to the availability of effective vectors and suitable habitats. Armigeres&nbsp;subalbatus (Coquillett, 1898), a common and neglected species, is of increasing interest given its potential vector capacity for Zika virus. However, potential distribution patterns and the underlying driving factors of Ar. subalbatus remain unknown. In the current study, detailed maps of their potential distributions were developed under both the current as well as future climate change scenarios (SSP126 and SSP585) based on CMIP6 data, employing the MaxEnt model. The results showed that the distribution of the Ar. subalbatus was mainly affected by temperature. Mean diurnal range was the strongest predictor in shaping the distribution of Ar. subalbatus, with an 85.2% contribution rate. By the 2050s and 2070s, Ar. subalbatus will have a broader potential distribution across China. There are two suitable expansion types under climate change in the 2050s and 2070s. The first type is continuous distribution expansion, and the second type is sporadic distribution expansion. Our comprehensive analysis of Ar. subalbatus&rsquo;s suitable distribution areas shifts under climate change and provides useful and insightful information for developing management strategies for future arboviruses

A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy

Abstract As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice

Additional file 1 of Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T1-weighted magnetic resonance imaging contrast agent

Additional file 1: Table S1. Synthesis conditions and characterization results of Gd-HPMAs. Table S2. Synthesis conditions and characterization results of Gd-HPMAs. Table S3. Large scale synthesis conditions and characterization results of Gd-HPMAs. Table S4. Specifications, dosages, and physicochemical properties for commercial contrast agents. Table S5. Physicochemical properties and characterization results for the Gd-HPMA30 formulation with adjuvants after high-temperature sterilization. Table S6. Acute systemic toxicity of the Gd-HPMA30 formulation after i.v. administration. Fig. S1. T1 relaxation rate plotted as a function of CGd for aqueous solutions of Gd-HPMA1-9 at 25 ℃ measured at 3.0 T. Fig. S2. T2 relaxation rate plotted as a function of CGd for aqueous solutions of Gd-HPMA1-9 at 25 ℃ measured at 3.0 T. Fig. S3. Influence of the Gd/HPMA molar ratio A or the pH value B on the r1 value and r2/r1 ratio. Mean ± SD, n = 3. Fig. S4. T1-weighted MR images of Gd-HPMA1-9 with various CGd (0 ~ 200 μM) observed by a 3.0 T clinical MRI system. Fig. S5. T1 A–D or T2 relaxation rate E–H plotted as a function of CGd for Gd-HPMA10-13 at 3.0 T. Fig. S6. T1 A–D or T2 relaxation rate E–H plotted as a function of CGd for Gd-HPMA10-13 at 7.0 T. Fig. S7. Zeta potential of Gd-HPMA12. Fig. S8. MRI of cancer cells in vitro. Fig. S9. Viabilities of 4T1 cells treated with Gd-HPMA12 compared with Gadavist® in a Gd concentration range of 0–250 µg/mL. Mean ± SD, n = 3. Fig. S10. Hemolysis ratio induced by Gd-HPMA12 in a Gd concentration range of 0-500 µg/mL compared with pure water and PBS. Mean ± SD, n = 3. Fig. S11. Blood routine analyses of heathy mice at day 1.0, 7.0, or 21 post-injection (i.v.) of PBS, or Gd-HPMA12 (Gd dosage = 5.0 mg/kg). Mean ± SD, n = 3. The blood routine analyses include the following indicators: hematocrit (HCT), hemoglobin (HGB), lymphocyte count (Lymph#), mean corpusular hemoglobin (MCH), mean corpusular hemoglobin concerntration (MCHC), mean corpusular volume (MCV), mean platelet volume (MPV), platelet count (PLT), neutrophil ratio (Gran#), red blood cell (RBC), and white blood cell (WBC). Fig. S12. Excreted Gd content in urine or feces of healthy SD mice within 24 h after i.v. injection of Gd-HPMA12. Gd dosage = 5.0 mg/kg. Mean ± SD, n = 3. Fig. S13. Blood clearance profiles of Gd-HPMA12 in healthy Balb/c mice by tracking the Gd concentration in blood at different time intervals after i.v. injection (n = 3). Fig. S14. Biodistribution of Gd level in 4T1 tumor-bearing mice at 1.0 or 12 h post-injection of Gd-HPMA12 via tail vein. Gd dosage = 5.0 mg/kg. Mean ± SD, n = 3. Fig. S15. Histological analyses of main organs (H and E staining) obtained from healthy mice at day 2.0 post-injection (i.v.) of PBS, or Gd-HPMA12. Fig. S16. 1/T1 or 1/T2 relaxation rate plotted as a function of CGd for Gd-HPMA14-29 at 7.0 T. Fig. S17. The black and white images of T1-weighted MR images of Gd-HPMA14-29 with various CGd (0 ~ 200 μM) observed by a 7.0 T clinical MRI system. Fig. S18. The pseudo-color images of T1-weighted MR images for Gd-HPMA14-29 with various CGd (0 ~ 200 μM) observed by a 7.0 T MRI scanner. Fig. S19. 1/T1 or 1/T2 relaxation rate plotted as a function of CGd for Gd-HPMA30. Magnetic field = 7.0 T. Fig. S20. The black and white and corresponding pseudo-color images of T1-weighted MR images for Gd-HPMA30 macrochelate with various CGd (0 ~ 200 μM) observed by a 7.0 T MRI scanner

Additional file 1 of A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy

Supplementary Material

Mating harassment may boost the effectiveness of the sterile insect technique for Aedes mosquitoes

Abstract The sterile insect technique is based on the overflooding of a target population with released sterile males inducing sterility in the wild female population. It has proven to be effective against several insect pest species of agricultural and veterinary importance and is under development for Aedes mosquitoes. Here, we show that the release of sterile males at high sterile male to wild female ratios may also impact the target female population through mating harassment. Under laboratory conditions, male to female ratios above 50 to 1 reduce the longevity of female Aedes mosquitoes by reducing their feeding success. Under controlled conditions, blood uptake of females from an artificial host or from a mouse and biting rates on humans are also reduced. Finally, in a field trial conducted in a 1.17 ha area in China, the female biting rate is reduced by 80%, concurrent to a reduction of female mosquito density of 40% due to the swarming of males around humans attempting to mate with the female mosquitoes. This suggests that the sterile insect technique does not only suppress mosquito vector populations through the induction of sterility, but may also reduce disease transmission due to increased female mortality and lower host contact