CD8+ Trms against malaria liver-stage: prospects and challenges

Attenuated sporozoites provide a valuable model for exploring protective immunity against the malarial liver stage, guiding the design of highly efficient vaccines to prevent malaria infection. Liver tissue-resident CD8+ T cells (CD8+ Trm cells) are considered the host front-line defense against malaria and are crucial to developing prime-trap/target strategies for pre-erythrocytic stage vaccine immunization. However, the spatiotemporal regulatory mechanism of the generation of liver CD8+ Trm cells and their responses to sporozoite challenge, as well as the protective antigens they recognize remain largely unknown. Here, we discuss the knowledge gap regarding liver CD8+ Trm cell formation and the potential strategies to identify predominant protective antigens expressed in the exoerythrocytic stage, which is essential for high-efficacy malaria subunit pre-erythrocytic vaccine designation

The pharmacokinetic and residue depletion study of eugenol in carp (Cyprinus carpio)

IntroductionThe pharmacokinetic profile and residue depletion of eugenol in carp (Cyprinus carpio) tissues and plasma were performed by a convenient and reliable high-performance liquid chromatography (HPLC) method.MethodsThe eugenol in carp tissues and plasma was extracted with a mixed solution of acetonitrile and methanol. N-hexane was used to remove lipid impurities. The method was successfully applied to the pharmacokinetic and residue elimination of eugenol in carp after the carp was administered a medicated bath.ResultsThe average recoveries of eugenol in tissues and plasma fortified with four concentration levels were 69.0–106.6% and 80.0–86.7%, respectively. The relative standard deviations were < 8.9%. The limit of detection (LOD) was 0.01 μg/g in tissue and 0.008 μg/ml in plasma, respectively. The pharmacokinetic parameter of Cmax for eugenol in plasma at the concentrations of 20, 35, and 75 mg/L were 10.86, 17.21, and 37.32 mg/L, respectively. The t1/2 values were 3.68, 4.22, and 9.31 h. After the investigation of the anesthetic effect, 35 mg/L of eugenol was the optimal concentration for anesthesia. The highest accumulation concentration of eugenol in carp is in the liver and the lowest is in the muscle. In addition, the eugenol in tissue was eliminated rapidly and at a lower level than the LOD at 48 h. According to the residue elimination, the withdrawal time of eugenol was suggested at 5.2 days.DiscussionThese results indicate that the developed method had good linearity and accuracy, and is sensitive enough for the monitoring of eugenol residue in carp. The half-life of eugenol decreased with the increase in drug concentration and the eugenol was eliminated rapidly in carp tissues. 35 mg/L eugenol was recommended as an anesthetic in carp due to its favorable anesthetic effect and no mortality. This study will contribute to the establishment of MRL regulation and setting a withdrawal period

Optimal Sr-Doped Free TiO2@SrTiO3 Heterostructured Nanowire Arrays for High-Efficiency Self-Powered Photoelectrochemical UV Photodetector Applications

Due to their high performance, photoelectrochemical ultraviolet (UV) photodetectors have attracted much attention, but the recombination of photogenerated electrons at the interface of photoanode/electrolyte limited further improvement of photoelectrochemical UV photodetectors (PEC UVPDs). Modification of TiO2 photoanode by SrTiO3 could improve the performance of UVPD, because the energy barrier that is established at the TiO2–SrTiO3 interface could accelerate the separation of the photogenerated electrons-holes pair. However, the recombination center that is caused by the preparation of TiO2@SrTiO3 core-shell heterostructured nanostructure decreases the performance of PEC UVPDs, which is still an important problem that hindered its application in PEC UVPDs. In this paper, we presented a Sr-doped free TiO2@SrTiO3 core-shell heterostructured nanowire arrays as a photoanode for the self-powered PEC UVPD. This will not only accelerate the separation of the photogenerated electrons-holes pair, but it will also reduce the recombination of photogenerated electron-hole pairs in the photoanode. The intrinsic effect of SrTiO3 reaction time on the J variations of UVPDs is investigated in detail. An impressive responsivity of 0.358 A·W−1 was achieved at 360 nm for the UVPD based on TiO2@SrTiO3 core-shell heterostructured nanowire arrays, which heretofore is a considerably high photoresponsivity for self-powered photoelectrochemical UVPDs. Additionally, this UVPD also exhibits a high on/off ratio, fast response time, excellent visible-blind characteristic, and linear optical signal response

Modification of TiO₂ Nanowire Arrays with Sn Doping as Photoanode for Highly Efficient Dye-Sensitized Solar Cells

The dye-sensitized solar cell (DSSC) is one candidate among the third-generation solar cells. The performance of most DSSCs based on TiO2 photoanode was limited by the low electron mobility within TiO2. To produce a much higher power conversion efficiency, Sn-doped TiO2 nanowire arrays were successfully prepared using a simple hydrothermal process. It was found that Sn doping augments electron mobility well and raises the flat band potential to improve the performance of DSSCs. The power conversion efficiency (η) of a DSSC based on the reasonable Sn-doped TiO2, N719 dye, platinized counter electrode and iodide/triiodide electrolyte reaches 8.75%. Furthermore, with an anatase TiO2 light scattering layer, a DSSC based on the Sn-doped TiO2 NWAs exhibits a remarkable power conversion efficiency of 9.43%, which is especially useful in weak light conditions

Determination of benefits of cochlear implantation in children with auditory neuropathy.

Auditory neuropathy (AN) is a recently recognized hearing disorder characterized by intact outer hair cell function, disrupted auditory nerve synchronization and poor speech perception and recognition. Cochlear implants (CIs) are currently the most promising intervention for improving hearing and speech in individuals with AN. Although previous studies have shown optimistic results, there was large variability concerning benefits of CIs among individuals with AN. The data indicate that different criteria are needed to evaluate the benefit of CIs in these children compared to those with sensorineural hearing loss. We hypothesized that a hierarchic assessment would be more appropriate to evaluate the benefits of cochlear implantation in AN individuals.Eight prelingual children with AN who received unilateral CIs were included in this study. Hearing sensitivity and speech recognition were evaluated pre- and postoperatively within each subject. The efficacy of cochlear implantation was assessed using a stepwise hierarchic evaluation for achieving: (1) effective audibility, (2) improved speech recognition, (3) effective speech, and (4) effective communication.The postoperative hearing and speech performance varied among the subjects. According to the hierarchic assessment, all eight subjects approached the primary level of effective audibility, with an average implanted hearing threshold of 43.8 ± 10.2 dB HL. Five subjects (62.5%) attained the level of improved speech recognition, one (12.5%) reached the level of effective speech, and none of the subjects (0.0%) achieved effective communication.CIs benefit prelingual children with AN to varying extents. A hierarchic evaluation provides a more suitable method to determine the benefits that AN individuals will likely receive from cochlear implantation

Loading MiR-210 in Endothelial Progenitor Cells Derived Exosomes Boosts Their Beneficial Effects on Hypoxia/Reoxygeneation-Injured Human Endothelial Cells via Protecting Mitochondrial Function

Background/Aims: Stem cell-derived exosomes (EXs) offer protective effects on various cells via their carried microRNAs (miRs). Meanwhile, miR-210 has been shown to reduce mitochondrial reactive oxygen species (ROS) overproduction. In this study, we determined the potential effects of endothelial progenitor cell-derived EXs (EPC-EXs) on hypoxia/ reoxygenation (H/R) injured endothelial cells (ECs) and investigated whether these effects could be boosted by miR-210 loading. Methods: Human EPCs were used to generate EPC-EXs, or transfected with scrambler control or miR-210 mimics to generate EPC-EXssc and EPC-EXsmiR-210. H/R-injured human ECs were used as a model for functional analysis of EXs on apoptosis, viability, ROS production and angiogenic ability (migration and tube formation) by flow cytometry, MTT, dihydroethidium and angiogenesis assay kits, respectively. For mechanism analysis, the mitochondrion morphology, membrane potential (MMP), ATP level and the expression of fission/fusion proteins (dynamin-related protein 1: drp1 and mitofusin-2: mfn2) were assessed by using JC-1 staining, ELISA and western blot, respectively. Results: 1) Transfection of miR-210 mimics into EPCs induced increase of miR-210 in EPC-EXsmiR-210 without change of average size; 2) EPC-EXsmiR-210, but not EPC-EXs or EPC-EXssc, significantly elevated miR-210 level in ECs; 3) EPC-EXsmiR-210 were more effective than EPC-EXs and EPC-EXssc in reducing H/R-induced EC apoptosis, ROS overproduction and angiogenic dysfunction; 4) EPC-EXs decreased mitochondrial fragmentation, elevated MMP and ATP level, as well as improved mitochondrial mfn2 and drp1 dysregulation, which were more effective in EPC-EXsmiR-210. Conclusion: Our results suggest that EPC-EXs protect ECs against H/R injury via improving mitochondrial function and miR-210 enrichment could boost their effects

Loading MiR-210 in Endothelial Progenitor Cells Derived Exosomes Boosts Their Beneficial Effects on Hypoxia/Reoxygeneation-Injured Human Endothelial Cells via Protecting Mitochondrial Function

Background/Aims: Stem cell-derived exosomes (EXs) offer protective effects on various cells via their carried microRNAs (miRs). Meanwhile, miR-210 has been shown to reduce mitochondrial reactive oxygen species (ROS) overproduction. In this study, we determined the potential effects of endothelial progenitor cell-derived EXs (EPC-EXs) on hypoxia/ reoxygenation (H/R) injured endothelial cells (ECs) and investigated whether these effects could be boosted by miR-210 loading. Methods: Human EPCs were used to generate EPC-EXs, or transfected with scrambler control or miR-210 mimics to generate EPC-EXssc and EPC-EXsmiR-210. H/R-injured human ECs were used as a model for functional analysis of EXs on apoptosis, viability, ROS production and angiogenic ability (migration and tube formation) by flow cytometry, MTT, dihydroethidium and angiogenesis assay kits, respectively. For mechanism analysis, the mitochondrion morphology, membrane potential (MMP), ATP level and the expression of fission/fusion proteins (dynamin-related protein 1: drp1 and mitofusin-2: mfn2) were assessed by using JC-1 staining, ELISA and western blot, respectively. Results: 1) Transfection of miR-210 mimics into EPCs induced increase of miR-210 in EPC-EXsmiR-210 without change of average size; 2) EPC-EXsmiR-210, but not EPC-EXs or EPC-EXssc, significantly elevated miR-210 level in ECs; 3) EPC-EXsmiR-210 were more effective than EPC-EXs and EPC-EXssc in reducing H/R-induced EC apoptosis, ROS overproduction and angiogenic dysfunction; 4) EPC-EXs decreased mitochondrial fragmentation, elevated MMP and ATP level, as well as improved mitochondrial mfn2 and drp1 dysregulation, which were more effective in EPC-EXsmiR-210. Conclusion: Our results suggest that EPC-EXs protect ECs against H/R injury via improving mitochondrial function and miR-210 enrichment could boost their effects

Expansion of C4 plants in South China and evolution of East Asian monsoon since 35 Ma: Black carbon records in the northern South China Sea

International audienceThe emergence and expansion of terrestrial C4 vegetation represent the most striking evolutionary adaptation of ecosystems to climate change during the Cenozoic. However, the long-term history of terrestrial C4 ecosystem expansion in East Asia remains poorly documented, and its links to tectonic and/or climate changes remain unclear due to the complexity of its forcing factors. Here, we reconstruct the long-term evolution of terrestrial C3–C4 plants biomass in South China since the late Eocene using continuous records of the stable carbon isotopic compositions (δ13C) of black carbon extracted from sediments at International Ocean Discovery Program (IODP) Site U1501 in the northern South China Sea (SCS). This study reveals remarkable stepwise expansions of C4 plants in South China at ∼20 Ma and 15 Ma with a gradual expansion trend at 7–4 Ma. We demonstrate that stepwise drying (long-term weakening of the East Asian summer monsoon and simultaneous strengthening of the East Asian winter monsoon), as well as the enhanced seasonality of precipitation, is responsible for the ecological evolution in South China since the early Miocene. Our black carbon records, combined with previous studies, indicate a coupled evolution of East Asian drying, vegetation shifts and global cooling. We suggest that the major Asian topography framework was established before the middle Miocene, and global cooling overwhelmed tectonic controls of the long-term evolution of the East Asian monsoon thereafter. This study highlights that both Tibetan uplift and global cooling have played a significant role in the long-term evolution of regional climate and vegetation