A modified perioperative regimen for deceased donor kidney transplantation in presensitized recipients without prior desensitization therapy

BackgroundRenal transplantation in HLA-presensitized recipients entails an increased risk of antibody-mediated rejection (AMR) and graft loss. There is currently no accepted standard treatment protocol that can help transplant surgeons safely perform deceased donor (DD) kidney transplantation in presensitized patients without pretransplant desensitization.MethodsFifty-one panel-reactive antibody (PRA)-positive recipients and 62 PRA-negative retransplant recipients (control) who received DD renal transplantation were included. Patients in the presensitized group (donor-specific antibody [DSA]-positive, n=25; DSA-negative, n=26) without desensitization received a modified perioperative treatment starting on day 0 or -1 with rituximab, thymoglobulin, and low daily doses of intravenous immunoglobulin (IVIG, 10-20 g/d, for 14 days). Plasmapheresis was performed once before surgery in DSA-positive recipients.ResultsThe median follow-up time was 51 months in the presensitized group and 41 months in the control group. The incidence of early acute rejection (AR) and AMR (including mixed rejection) was 35.3% and 13.7% in the presensitized group, respectively, significantly higher than in the control group (14.5% and 1.6%, respectively). Within the presensitized group, the DSA-positive subgroup had more AMR than the DSA-negative subgroup (24.0% vs. 3.8%), but the incidence of T cell-mediated rejection was comparable (20.0% vs. 23.4%). In the presensitized group, all rejections were successfully reversed, and graft function remained stable during follow-up. The 1-year and 3-year survival rates of the grafts and recipients in this group were 98.0%.ConclusionWith a modified IVIG-based perioperative regimen, excellent intermediate-term graft and recipient survival outcomes can be achieved in presensitized patients who received DD kidney transplantation without prior desensitization

Dielectric Breakdown in Chemical Vapor Deposited Hexagonal Boron Nitride

Insulating films are essential in multiple electronic devices because they can provide essential functionalities, such as capacitance effects and electrical fields. Two-dimensional (2D) layered materials have superb electronic, physical, chemical, thermal, and optical properties, and they can be effectively used to provide additional performances, such as flexibility and transparency. 2D layered insulators are called to be essential in future electronic devices, but their reliability, degradation kinetics, and dielectric breakdown (BD) process are still not understood. In this work, the dielectric breakdown process of multilayer hexagonal boron nitride (h-BN) is analyzed on the nanoscale and on the device level, and the experimental results are studied via theoretical models. It is found that under electrical stress, local charge accumulation and charge trapping/detrapping are the onset mechanisms for dielectric BD formation. By means of conductive atomic force microscopy, the BD event was triggered at several locations on the surface of different dielectrics (SiO2, HfO2, Al2O3, multilayer h-BN, and monolayer h-BN); BD-induced hillocks rapidly appeared on the surface of all of them when the BD was reached, except in monolayer h-BN. The high thermal conductivity of h-BN combined with the one-atom-thick nature are genuine factors contributing to heat dissipation at the BD spot, which avoids self-accelerated and thermally driven catastrophic BD. These results point to monolayer h-BN as a sublime dielectric in terms of reliability, which may have important implications in future digital electronic devices.Fil: Jiang, Lanlan. Soochow University; ChinaFil: Shi, Yuanyuan. Soochow University; China. University of Stanford; Estados UnidosFil: Hui, Fei. Soochow University; China. Massachusetts Institute of Technology; Estados UnidosFil: Tang, Kechao. University of Stanford; Estados UnidosFil: Wu, Qian. Soochow University; ChinaFil: Pan, Chengbin. Soochow University; ChinaFil: Jing, Xu. Soochow University; China. University of Texas at Austin; Estados UnidosFil: Uppal, Hasan. University of Manchester; Reino UnidoFil: Palumbo, Félix Roberto Mario. Comisión Nacional de Energía Atómica; Argentina. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lu, Guangyuan. Chinese Academy of Sciences; República de ChinaFil: Wu, Tianru. Chinese Academy of Sciences; República de ChinaFil: Wang, Haomin. Chinese Academy of Sciences; República de ChinaFil: Villena, Marco A.. Soochow University; ChinaFil: Xie, Xiaoming. Chinese Academy of Sciences; República de China. ShanghaiTech University; ChinaFil: McIntyre, Paul C.. University of Stanford; Estados UnidosFil: Lanza, Mario. Soochow University; Chin

A Brassica napus Reductase Gene Dissected by Associative Transcriptomics Enhances Plant Adaption to Freezing Stress

Cold treatment (vernalization) is required for winter crops such as rapeseed (Brassica napus L.). However, excessive exposure to low temperature (LT) in winter is also a stress for the semi-winter, early-flowering rapeseed varieties widely cultivated in China. Photosynthetic efficiency is one of the key determinants, and thus a good indicator for LT tolerance in plants. So far, the genetic basis underlying photosynthetic efficiency is poorly understood in rapeseed. Here the current study used Associative Transcriptomics to identify genetic loci controlling photosynthetic gas exchange parameters in a diversity panel comprising 123 accessions. A total of 201 significant Single Nucleotide Polymorphisms (SNPs) and 147 Gene Expression Markers (GEMs) were detected, leading to the identification of 22 candidate genes. Of these, Cab026133.1, an ortholog of the Arabidopsis gene AT2G29300.2 encoding a tropinone reductase (BnTR1), was further confirmed to be closely linked to transpiration rate. Ectopic expressing BnTR1 in Arabidopsis plants significantly increased the transpiration rate and enhanced LT tolerance under freezing conditions. Also, a much higher level of alkaloids content was observed in the transgenic Arabidopsis plants, which could help protect against LT stress. Together, the current study showed that AT is an effective approach for dissecting LT tolerance trait in rapeseed and that BnTR1 is a good target gene for the genetic improvement of LT tolerance in plant

Comparison of the Distinct, Host-Specific Response of Three Solanaceae Hosts Induced by <i>Phytophthora infestans</i>

Three Solanaceae hosts (TSHs), S. tuberosum, N. benthamiana and S. lycopersicum, represent the three major phylogenetic clades of Solanaceae plants infected by Phytophthora infestans, which causes late blight, one of the most devastating diseases seriously affecting crop production. However, details regarding how different Solanaceae hosts respond to P. infestans are lacking. Here, we conducted RNA-seq to analyze the transcriptomic data from the TSHs at 12 and 24 h post P. infestans inoculation to capture early expression effects. Macroscopic and microscopic observations showed faster infection processes in S. tuberosum than in N. benthamiana and S. lycopersicum under the same conditions. Analysis of the number of genes and their level of expression indicated that distinct response models were adopted by the TSHs in response to P. infestans. The host-specific infection process led to overlapping but distinct in GO terms and KEGG pathways enriched for differentially expressed genes; many were tightly linked to the immune response in the TSHs. S. tuberosum showed the fastest response and strongest accumulation of reactive oxygen species compared with N. benthamiana and S. lycopersicum, which also had similarities and differences in hormone regulation. Collectively, our study provides an important reference for a better understanding of late blight response mechanisms of different Solanaceae host interactions

Involvement of Actin-Regulating Factor Cofilin in the Inclusion Body Formation and RNA Synthesis of Human Parainfluenza Virus Type 3 via Interaction With the Nucleoprotein

Human parainfluenza virus type 3 (HPIV3) is one of the primary pathogens that causing severe respiratory tract diseases in newborns and infants. It could induce inclusion bodies (IBs) in infected cells. Comprised of viral nucleoprotein (N) and phosphoprotein (P), as well as some cellular factors, HPIV3 IBs are unique platform for efficient viral synthesis. Although several studies have demonstrated the formation of IBs, little is known about cellular proteins involved in HPIV3 IBs formation. By quantitative real-time PCR assays after cytochalasin D treatment, we found actin microfilaments of the cytoskeleton were indispensible for HPIV3 RNA synthesis. Using co-immunoprecipitation and immunofluorescence assays, an actin-modulating protein, cofilin was found to involve in the IBs formation through interaction with the N protein in N–P induced IBs complex. Viral IBs formation reduced upon RNA interference knockdown of cellular cofilin, thus viral RNA synthesis and protein expression level were also suppressed. What’s more, the inactive form of cofilin, p-cofilin was increased after HPIV3 infection, and phosphorylation of cofilin was required for interacting with N–P complex and IBs formation. We further identified that the regions in cofilin interacting with N protein lies in the C-terminus. Our findings for the first time to state that cellular cofilin involves in HPIV3 IBs and interaction with N is critical for cofilin to aid IBs formation and enhancing viral RNA synthesis

Single femoral artery access is safe and feasible during transcatheter aortic valve replacement: a propensity score matched analysis

BackgroundTranscatheter aortic valve replacement (TAVR) potentially may be significantly simplified by using the single artery access (SA) technique, which does not require a secondary artery access. Nevertheless, the safety and efficacy of this technique remains unclear. Our goal was to determine if single artery access TAVR (without upgrading the sheath size) is a feasible, minimally invasive procedure.MethodsPatients with symptomatic severe aortic stenosis who underwent TAVR via the femoral artery were consecutively enrolled in this study. Eligible individuals were divided into 2 groups: the SA group and the dual artery access (DA) group. The primary end point was device success (defined by the valve academic research consortium 3, VARC 3). A 6-month follow-up and propensity score matching analyses were performed.ResultsAfter propensity score matching analysis, a total of 130 patients were included: 65 in the SA group and 65 in the DA group. The SA procedure achieved similar device success (95.4% vs. 87.7%; P = 0.115) compared with the DA procedure. The SA procedure shortened the operating time (102 min vs. 125 min; P = 0.001) but did not increase the x-ray time or dose. Both a 20 Fr and a 22 Fr sheath (without upgrading the sheath size) could be used for the SA procedure. There was no major vascular complication occurred in both groups. The incidence of minor main vascular and access complications in the SA group was comparable to those of the DA procedure (0.0% vs. 3.1%; P = 0.156).ConclusionsThe SA access procedure is a promising minimally invasive TAVR technique with a low incidence of vascular complications and a high incidence of device success. It is safe and possibly applicable in all TAVR procedures

Upregulation of Heme Oxygenase-1 Endues Immature Dendritic Cells With More Potent and Durable Immunoregulatory Properties and Promotes Engraftment in a Stringent Mouse Cardiac Allotransplant Model

Heme oxygenase-1 (HO-1) is critical for the ability of immature dendritic cells (imDCs) to suppress T-cell responses. Induction of high HO-1 expression may markedly improve the tolerogenic capacity of imDCs. Here, we generated bone marrow-derived DCs (BMDCs) from BALB/c mice with low doses of GM-CSF and IL-4. The adherent BMDCs were obtained as imDCs. Upregulation of HO-1 in imDCs (HO-1hi-imDCs) was achieved by cobalt protoporphyrin treatment. HO-1hi-imDCs proved to be more maturation-resistant than conventional imDCs, with an enhanced ability to inhibit allogeneic T-cell proliferation stimulated by anti-CD3/CD28 antibodies. When donor-derived DC adoptive transfer was performed in a stringent mouse cardiac allotransplant model, the extent of graft prolongation observed with HO-1hi imDCs was superior to that obtained with conventional imDCs. T-cell activation and proliferation in cardiac allograft recipients was more strongly suppressed in the HO-1hi imDC transfusion group than that in the untreated imDC group. Furthermore, donor HO-1hi imDCs were able to maintain a status of high HO-1 expression and survived longer in the recipient spleens than did untreated imDCs after adoptive transfer. In vitro-generated HO-1hi imDCs had an enhanced tolerogenic capacity to modulate alloimmune responses both in vitro and in vivo, and thus may offer a novel antigen-specific and cost-effective strategy to induce transplant tolerance

Preferential Growth of Semiconducting Single-Walled Carbon Nanotubes on Substrate by Europium Oxide

In this paper, we have demonstrated that europium oxide (Eu2O3) is a new type of active catalyst for single-walled carbon nanotubes (SWNTs) growth under suitable conditions. Both random SWNT networks and horizontally aligned SWNT arrays are efficiently grown on silicon wafers. The density of the SWNT arrays can be altered by the CVD conditions. This result further provides the experimental evidence that the efficient catalyst for SWNT growth is more size dependent than the catalysts themselves. Furthermore, the SWNTs from europium sesquioxides have compatibly higher quality than that from Fe/Mo catalyst. More importantly, over 80% of the nanotubes from Eu2O3 are semiconducting SWNTs (s-SWNTs), indicating the preferential growth of s-SWNTs from Eu2O3. This new finding could open a way for selective growth of s-SWNTs, which can be used as high-current nanoFETs and sensors. Moreover, the successful growth of SWNTs by Eu2O3 catalyst provides new experimental information for understanding the preferential growth of s-SWNTs from Eu2O3, which may be helpful for their controllable synthesis