Search

Introduction: Granulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. Methods: G-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in GMDSCs were analyzed via RNA sequencing to investigate functional transitions. Results: G-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. Conclusion: Our findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD. [ABSTRACT FROM AUTHOR]

During the last decade, the underlying pathogenic mechanisms of acute myeloid leukemia (AML) have been the subject of extensive study which has considerably increased our understanding of the disease. However, both resistance to chemotherapy and disease relapse remain the principal obstacles to successful treatment. Because of acute and chronic undesirable effects frequently associated with conventional cytotoxic chemotherapy, consolidation chemotherapy is not feasible, especially for elderly patients, which has attracted a growing body of research to attempt to tackle this problem. Immunotherapies for acute myeloid leukemia, including immune checkpoint inhibitors, monoclonal antibodies, dendritic cell (DC) vaccines, together with T-cell therapy based on engineered antigen receptor have been developed recently. Our review presents the recent progress in immunotherapy for the treatment of AML and discusses effective therapies that have the most potential and major challenges. [ABSTRACT FROM AUTHOR]

Objective: To clarify the mechanism of triptolide (TP) in alleviating the conditions underlying SLE. Methods: Eight-week-old MRL/lpr mice were randomly divided into a model group (n = 5), low-doseTP (TP-L) group (n = 5), and high-doseTP (TP-H) group (n = 5). Mice in these groups were gavaged with normal saline, low-dose TP solution, and high-dose TP solution for 8 weeks, respectively. The expression levels of anti-dsDNA, IgG, IgM, IgA, C3, C4, and CREA, BUN, ALT, AST, ALB, and ALP indexes in the serum of mice were detected. The proportion of CD19+CD138+B220- cells in the spleen and the pathological changes of kidney tissue in the mice were also evaluated. The possible signaling pathways and microRNA (miRNA) targets of TP in the treatment of SLE were analyzed using network pharmacology. The expressions of TLR7 mRNA and miR-146a in Raji cells (a B lymphocyte line) were detected using qPCR before and after intervention with a miR-146a inhibitor. The protein expression levels of TLR7, MyD88, p-IRAK1, and p-NF-κBp65 were detected using western blot analysis. Results: TP could significantly decrease the levels of ds-DNA and IgG, alleviate pathological injury in renal tissue, and upregulate miR-146a expression in the B cells of MRL/lpr mice without obvious liver and kidney toxicity. Network pharmacology analysis showed that TP could mainly regulate the Toll-like receptor signaling pathway, and NF-κB signaling pathway, among others. miRNA target prediction suggested that TP could regulate miRNAs such as miR-146a. In vitro cell experiments further confirmed that TP could significantly upregulate miR-146a expression and downregulate the expression of TLR7 mRNA and protein levels TLR7, MyD88, p-IRAK1, and p-NF-κBp65. After intervention with a miR-146a inhibitor, TP had no obvious inhibitory effects on TLR7, MyD88, p-IRAK1, and p-NF-κBp65 expression. Conclusion: TP may exert therapeutic effects on SLE by regulating miR-146a expression, inhibiting the TLR7/NF-KB signaling pathway, and affecting B cell activation. [ABSTRACT FROM AUTHOR]

This paper presents a new energy management system based on equivalent consumption minimization strategy (ECMS) for hybrid electric vehicles. The aim is to enhance fuel economy and impose state of charge (SoC) charge-sustainability. First, the relationship between the equivalent factor (EF) of ECMS and the co-state of pontryagin's minimum principle (PMP) is derived. Second, a new method of implementing the adaptation law using fuzzy proportional plus integral (PI) controller is developed to adjust EF for ECMS in real-time. This adaptation law is more robust than one with constant EF due to the variation of EF as well as driving cycle. Finally, simulations for two driving cycles using ECMS are conducted as opposed to the commonly used rule-based (RB) control strategy, indicating that the proposed adaptation law can provide a promising blend in terms of fuel economy and charge-sustainability. The results confirm that ECMS with Fuzzy PI adaptation law is more robust than ECMS with constant EF as well as PI adaptation law and it achieves significant improvements compared with RB in terms of fuel economy, which is enhanced by 4.44% and 14.7% for china city bus cycle and economic commission of Europe (ECE) cycle, respectively. [ABSTRACT FROM AUTHOR]

Jurassic to Cretaceous clastic rocks of the South Turgay Basin were deposited in the typical Mesozoic rift basin formed during the late Triassic collision between the Kazakstan and Siberia plates. In this study, we used more than 140 wells and 2400 km2 of 3D seismic data in the northern Aryskum Depression to produce a detailed sequence stratigraphic interpretation of the South Turgay Basin. Guided by sequence stratigraphy, sedimentology, and structural geology, lower Jurassic-lower Cretaceous strata of the northern Aryskum Depression in the South Turgay Basin, Kazakhstan were subdivided into 10 third-order sequences based on geological and geophysical data. Combined with tectonic evolution characteristics, sequence developments in the basin can be divided into four stages: early rift stage (SQ1-SQ3), late rift stage (SQ4-SQ6), fault to depression transition stage (SQ7-SQ8), and depression stage (SQ9-SQ10). Through comprehensive analysis of seismic sequence configuration, sequence stacking pattern, and depositional filling characteristics, we established the depositional model of the Aryskum Depression in the South Turgay Basin. It is indicated that there are differences in depositional compositions of sequences formed in different stages. Four stages can be clearly identified: filling stage of fan delta facies-lacustrine facies (Stage I) corresponding to the rapid filling in the early rift stage, filling stage of fan delta facies-lacustrine facies-normal delta facies (Stage II) corresponding to trichotomous characteristics of internal systems tracts in the late rift stage, filling stage of braided river delta facies-normal delta facies-lacustrine facies (Stage III) corresponding to the development of high-stand systems tracts in the fault to depression transition stage, and filling stage of fluvial facies-normal delta facies-lacustrine facies (Stage IV) corresponding to binary characteristics of internal systems tracts in the depression stage. Finally, optimization of favorable exploration strata and prospects in the Aryskum Depression are proposed. [ABSTRACT FROM AUTHOR]

Determining the spatio-temporal distribution of the deformation tied to the India-Eurasian convergence and the impact of pre-existing weaknesses on the Cenozoic crustal deformation is significant for understanding how the convergence between India and Eurasia contributed to the development of the Tibetan Plateau. The exhumation history of the northeastern Tibetan Plateau was addressed in this research using a new apatite fission track (AFT) study in the North Qaidam thrust belt (NQTB). Three granite samples collected from the Qaidam Shan pluton in the north tied to the Qaidam Shan thrust, with AFT ages clustering in the Eocene to Miocene. The other thirteen samples obtained from the Luliang Shan and Yuka plutons in the south related to the Luliang Shan thrust and they have showed predominantly the Cretaceous AFT ages. Related thermal history modeling based on grain ages and track lengths indicates rapid cooling events during the Eocene-early Oligocene and since late Miocene within the Qaidam Shan, in contrast to those in the Cretaceous and since the Oligocene-Miocene in the Luliang Shan and Yuka region. The results, combined with published the Cretaceous thermochronological ages in the Qaidam Shan region, suggest that the NQTB had undergo rapid exhumation during the accretions along the southern Asian Andean-type margin prior to the India-Eurasian collision. The Cenozoic deformation initially took place in the North Qaidam thrust belt by the Eocene, which is consistent with the recent claim that the deformation of the northeastern Tibetan Plateau initiated in the Eocene as a response to continental collision between India and Eurasia. The immediate deformation responding to the collision is tentatively attributed to the pre-existing weaknesses of the lithosphere, and therefore the deformation of the northeastern Tibetan Plateau should be regarded as a boundary-condition-dependent process. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the effects of thymidylate synthase (TYMS) and excision repair cross-complementing 1 (ERCC1) polymorphisms on chemotherapeutic efficacy in patients with gastrointestinal tumors using peripheral venous blood. Preoperative peripheral venous blood and tumor tissue samples of 43 patients with gastric cancer and the peripheral venous blood samples of 76 patients with cancer who underwent chemotherapy were studied. The 3R/3R and 2R/2R or 2R/3R genotypes of TYMS were identi- fied in 72.09 and 27.91%, respectively (P<0.01), of untreated patients, and the C/C and T/T or C/T genotypes of ERCC1 were present in 81.39 and 18.61%, respectively (P<0.01), of patients. The 3R/3R and 2R/2R or 2R/3R genotypes of TYMS were identified in 65.79 and 34.21%, respectively, of chemotherapy- treated patients. The overall response rates (ORRs) for the two aforementioned genotypes were 18.00 and 57.69%, respectively (P<0.01), and those for the C/C and T/T or C/T genotypes of ERCC1 were 63.16 and 36.84%, respectively. The ORRs were 47.91 and 3.57%, respectively (P<0.01). In conclusion, peripheral blood samples may be used to replace tumor tissue for detecting TYMS and ERCC1 polymorphisms, and may be used to evaluate the efficacy of 5-fluorouracil and platinum drugs. [ABSTRACT FROM AUTHOR]

Large scale syntheses of uniform metal nanoparticles with hollow porous structure have attracted much attention owning to their high surface area, abundant active sites and relatively efficient catalytic activity. Herein, we report a general method to synthesize hollow porous Pd nanospheres (Pd HPNSs) by templating sacrificial SiO2 nanoparticles with the assistance of polyallylamine hydrochloride (PAH) through layer-by-layer self-assembly. The chemically inert PAH is acting as an efficient stabilizer and complex agent to control the synthesis of Pd HPNSs, probably accounting for its long aliphatic alkyl chains, excellent coordination capability and good hydrophilic property. The physicochemical properties of Pd HPNSs are thoroughly characterized by various techniques, such as transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy. The growth mechanism of Pd HPNSs is studied based on the analysis of diverse experimental observations. The as-prepared Pd HPNSs exhibit clearly enhanced electrocatalytic activity and durability for the formic oxidation reaction (FAOR) in acid medium compared with commercial Pd black. [ABSTRACT FROM AUTHOR]

Background Plant disease resistance (R) genes with the nucleotide binding site (NBS) play an important role in offering resistance to pathogens. The availability of complete genome sequences of Brassica oleracea and Brassica rapa provides an important opportunity for researchers to identify and characterize NBS-encoding R genes in Brassica species and to compare with analogues in Arabidopsis thaliana based on a comparative genomics approach. However, little is known about the evolutionary fate of NBS-encoding genes in the Brassica lineage after split from A. thaliana. Results Here we present genome-wide analysis of NBS-encoding genes in B. oleracea, B. rapa and A. thaliana. Through the employment of HMM search and manual curation, we identified 157, 206 and 167 NBS-encoding genes in B. oleracea, B. rapa and A. thaliana genomes, respectively. Phylogenetic analysis among 3 species classified NBS-encoding genes into 6 subgroups. Tandem duplication and whole genome triplication (WGT) analyses revealed that after WGT of the Brassica ancestor, NBS-encoding homologous gene pairs on triplicated regions in Brassica ancestor were deleted or lost quickly, but NBS-encoding genes in Brassica species experienced species-specific gene amplification by tandem duplication after divergence of B. rapa and B. oleracea. Expression profiling of NBS-encoding orthologous gene pairs indicated the differential expression pattern of retained orthologous gene copies in B. oleracea and B. rapa. Furthermore, evolutionary analysis of CNL type NBS-encoding orthologous gene pairs among 3 species suggested that orthologous genes in B. rapa species have undergone stronger negative selection than those in B .oleracea species. But for TNL type, there are no significant differences in the orthologous gene pairs between the two species. Conclusion This study is first identification and characterization of NBS-encoding genes in B. rapa and B. oleracea based on whole genome sequences. Through tandem duplication and whole genome triplication analysis in B. oleracea, B. rapa and A. thaliana genomes, our study provides insight into the evolutionary history of NBS-encoding genes after divergence of A. thaliana and the Brassica lineage. These results together with expression pattern analysis of NBS-encoding orthologous genes provide useful resource for functional characterization of these genes and genetic improvement of relevant crops. [ABSTRACT FROM AUTHOR]

In our previous studies, we have proved that neutron irradiation can decrease the single event latch-up (SEL) sensitivity of CMOS SRAM. And one of the key contributions to the multiple cell upset (MCU) is the parasitic bipolar amplification, it bring us to study the impact of neutron irradiation on the SRAM’s MCU sensitivity. After the neutron experiment, we test the devices’ function and electrical parameters. Then, we use the heavy ion fluence to examine the changes on the devices’ MCU sensitivity pre- and post-neutron-irradiation. Unfortunately, neutron irradiation makes the MCU phenomenon worse. Finally, we use the electric static discharge (ESD) testing technology to deduce the experimental results and find that the changes on the WPM region take the lead rather than the changes on the parasitic bipolar amplification for the 90 nm process. [ABSTRACT FROM AUTHOR]

The pattern dependence in synergistic effects was studied in a 0.18 μm static random access memory (SRAM) circuit. Experiments were performed under two SEU test environments: 3 MeV protons and heavy ions. Measured results show different trends. In heavy ion SEU test, the degradation in the peripheral circuitry also existed because the measured SEU cross section decreased regardless of the patterns written to the SRAM array. TCAD simulation was performed. TID-induced degradation in nMOSFETs mainly induced the imprint effect in the SRAM cell, which is consistent with the measured results under the proton environment, but cannot explain the phenomena observed under heavy ion environment. A possible explanation could be the contribution from the radiation-induced GIDL in pMOSFETs. [ABSTRACT FROM AUTHOR]