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1.
Transplant Proc ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31918969

RESUMO

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the effects of granulocyte colony-stimulating factor (G-CSF) on the proliferation and apoptosis of bone marrow (BM) B cells from healthy donors and its mechanism. MATERIALS AND METHODS: The proliferation ability and apoptosis of BM cells from healthy donors before and after in vivo G-CSF application were determined by multiparameter flow cytometry. The gene expression of B cells was detected by RNA-Seq. In vitro experiments were performed to investigate the effects of G-CSF on the proliferation and apoptosis of BM B cells through which gene. RESULTS: Treating healthy donors with G-CSF significantly decreased proliferation and increased apoptosis of BM B cells. The proliferation of CD19+CD27- B cell subgroup and CD19+CD24hiCD38hi B cell subset were also decreased. G-CSF also significantly altered proapoptotic genes, cell cycle arrest genes, and DNA replication and cell cycle genes, especially significantly increased SOCS1 expression of BM B cells. In vitro experiments showed that SOCS1 overexpression did not affect B cell proliferation ability and apoptosis. CONCLUSIONS: Our results suggest that extensive effects of G-CSF on BM B cells, such as inhibiting proliferation, inducing apoptosis, and altering a series of gene expression.

2.
J Am Chem Soc ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31905287

RESUMO

Supramolecular polymers based on host-guest molecular recognition have emerged as promising platforms for the development of smart materials. However, the studies on them are primarily conducted in solution and/or in the gel state. In contrast, little is known about dynamic properties and applications of supramolecular polymers in bulk. Herein, we present a self-crosslinking supramolecular polymer network (SPN) as a model system to understand the bulk properties controlled by noncovalent interactions. Specifically, the SPN monomer is composed of two benzo-21-crown-7 (B21C7) host units and two dialkylammonium salt guest moieties on a four-arm core, wherein complementary host-guest complexation drives the formation of the SPN with [2]pseudorotaxane linkages between B21C7 and ammonium motifs. The dynamic and reversible behaviors of the linkages are evaluated by measurement of viscoelasticity. The results indicate that the host-guest molecular recognition becomes highly dynamic at elevated temperature. Moreover, the relatively high activation energy of the SPN manifests itself as a new type of thermo-plastic material with network topology freezing glass transition. Finally, we demonstrate how these findings provide insights into the malleability and processability of the SPN by simple demos. The fundamental understanding gained from the research on this SPN in bulk will facilitate the advancement and application of supramolecular materials.

3.
BMJ Open ; 10(1): e029653, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31915156

RESUMO

OBJECTIVE: To search for evidence of the relationship between occupational silica exposure and heart disease. DESIGN: A systematic review and meta-analysis. BACKGROUND: Growing evidence suggests a relationship between occupational silica exposure and heart disease; however, the link between them is less clear. DATA SOURCES: PubMed, ScienceDirect, Springer and EMBASE were searched for articles published between 1 January 1995 and 20 June 2019. Articles that investigated the effects of occupational silica exposure on the risk of heart disease were considered. STUDY SELECTION: We included cohort studies, including prospective, retrospective and retroprospective studies. DATA EXTRACTION AND SYNTHESIS: We extracted data using a piloted data collection form and conducted random-effects meta-analysis and exposure-response analysis. The meta-relative risk (meta-RR), a measure of the average ratio of heart disease rates in those with and without silica exposure, was used as an inverse variance-weighted average of relative risks from the individual studies. The Newcastle-Ottawa Quality Assessment Scale for cohort studies was used for study quality assessment. OUTCOME MEASURE: We calculated the risk of heart diseases such as pulmonary heart disease, ischaemic heart disease and others. RESULTS: Twenty cohort studies were included. The results suggest a significant increase in the risk of overall heart disease (meta-RR=1.08, 95% CI 1.03 to 1.13). Stronger evidence of association with pulmonary heart disease was found in the risk estimate of both categories of heart disease (meta-RR=1.24, 95% CI 1.08 to 1.43) and in the exposure-response analysis (meta-RR=1.39, 95% CI 1.19 to 1.62). Our subgroup analyses also revealed that the statistical heterogeneity among studies could be attributed mainly to the diversity in reference group, occupation and study quality score. CONCLUSIONS: Silica-exposed workers are at an increased risk for overall heart disease, especially pulmonary heart disease. Further research is needed to better clarify the relationship between occupational silica exposure and ischaemic heart disease. PROSPERO REGISTRATION NUMBER: CRD42019124673.

4.
Gigascience ; 9(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895412

RESUMO

BACKGROUND: Seasonal migration is one of the most spectacular events in nature; however, the molecular mechanisms related to this phenomenon have not been investigated in detail. The Chinese tapertail, or Japanese grenadier anchovy, Coilia nasus, is a valuable migratory fish of high economic importance and special migratory dimorphism (with certain individuals as non-migratory residents). RESULTS: In this study, an 870.0-Mb high-quality genome was assembled by the combination of Illumina and Pacific Biosciences sequencing. Approximately 812.1 Mb of scaffolds were linked to 24 chromosomes using a high-density genetic map from a family of 104 full siblings and their parents. In addition, population sequencing of 96 representative individuals from diverse areas along the putative migration path identified 150 candidate genes, which are mainly enriched in 3 Ca2+-related pathways. Based on integrative genomic and transcriptomic analyses, we determined that the 3 Ca2+-related pathways are critical for promotion of migratory adaption. A large number of molecular markers were also identified, which distinguished migratory individuals and non-migratory freshwater residents. CONCLUSIONS: We assembled a chromosome-level genome for the Chinese tapertail anchovy. The genome provided a valuable genetic resource for understanding of migratory adaption and population genetics and will benefit the aquaculture and management of this economically important fish.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31880904

RESUMO

Solid-state ionic approaches for modifying ion distributions in getter/oxide heterostructures offer exciting potentials to control material properties. Here, we report a simple, scalable approach allowing for manipulation of the superconducting transition in optimally doped YBa2Cu3O7-δ (YBCO) films via a chemically driven ionic migration mechanism. Using a thin Gd capping layer of up to 20 nm deposited onto 100 nm thick epitaxial YBCO films, oxygen is found to leach from deep within the YBCO. Progressive reduction of the superconducting transition is observed, with complete suppression possible for a sufficiently thick Gd layer. These effects arise from the combined impact of redox-driven electron doping and modification of the YBCO microstructure due to oxygen migration and depletion. This work demonstrates an effective step toward total ionic tuning of superconductivity in oxides, an interface-induced effect that goes well into the quasi-bulk regime, opening-up possibilities for electric field manipulation.

6.
Proc Natl Acad Sci U S A ; 117(1): 238-242, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31852824

RESUMO

With the recent discovery of the quantum anomalous Hall insulator (QAHI), which exhibits the conductive quantum Hall edge states without external magnetic field, it becomes possible to create a topological superconductor (SC) by introducing superconductivity into these edge states. In this case, 2 distinct topological superconducting phases with 1 or 2 chiral Majorana edge modes were theoretically predicted, characterized by Chern numbers (N) of 1 and 2, respectively. We present spectroscopic evidence from Andreev reflection experiments for the presence of chiral Majorana modes in an Nb/(Cr0.12Bi0.26Sb0.62)2Te3 heterostructure with distinct signatures attributed to 2 different topological superconducting phases. The results are in qualitatively good agreement with the theoretical predictions.

7.
Ying Yong Sheng Tai Xue Bao ; 30(12): 4259-4266, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31840472

RESUMO

Beak is one of the most hard tissues in cephalopods, which is important in the study of fishery ecology. We analyzed the morphological growth characteristics of 268 beaks of Gonatopsis borealis collected in the Northwest Pacific Ocean from September to November of 2018 by Chinese jigging fishing fleets. Results from the principal component analysis showed that the upper hood length (UHL), upper crest length (UCL), upper rostrum length (URL), lower hood length (LHL), lower crest length (LCL) and lower rostrum length (LRL) could be used as the morphological characteristic parameters to study the morphological growth of beak. Results from the analysis of covariance (ANCOVA) showed that there was no significant difference both in the relationships between the morphological characteristic parameters versus mantle length (ML) or body weight (BW) for males and females. The relationships between ML and UHL, LHL were best described by power functions but by logarithm function for UCL, URL, LCL, and linear function for LRL respectively. The relationships between BW and UHL, UCL, URL, LCL, LRL were best described by logarithm functions but power function for LHL based on the result of the Akaike's information criterion. The results of growth models for the morphological parameters in this study provided scientific basis for the stock assessment in further research.

8.
Adv Mater ; : e1906360, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805206

RESUMO

Protein-based structural biomaterials are of great interest for various applications because the sequence flexibility within the proteins may result in their improved mechanical and structural integrity and tunability. As the two representative examples, protein-based adhesives and fibers have attracted tremendous attention. The typical protein adhesives, which are secreted by mussels, sandcastle worms, barnacles, and caddisfly larvae, exhibit robust underwater adhesion performance. In order to mimic the adhesion performance of these marine organisms, two main biological adhesives are presented, including genetically engineered protein-based adhesives and biomimetic chemically synthetized adhesives. Moreover, various protein-based fibers inspired by spider and silkworm proteins, collagen, elastin, and resilin are studied extensively. The achievements in synthesis and fabrication of structural biomaterials by DNA recombinant technology and chemical regeneration certainly will accelerate the explorations and applications of protein-based adhesives and fibers in wound healing, tissue regeneration, drug delivery, biosensors, and other high-tech applications. However, the mechanical properties of the biological structural materials still do not match those of natural systems. More efforts need to be devoted to the study of the interplay of the protein structure, cohesion and adhesion effects, fiber processing, and mechanical performance.

9.
Int J Mol Sci ; 20(23)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31816902

RESUMO

Copper is a mineral element essential for the normal growth and development of plants; however, excessive levels can severely affect plant growth and development. Oryza sativa L. multiple stress-responsive gene 3 (OsMSR3) is a small, low-molecular-weight heat shock protein (HSP) gene. A previous study has shown that OsMSR3 expression improves the tolerance of Arabidopsis to cadmium stress. However, the role of OsMSR3 in the Cu stress response of plants remains unclear, and, thus, this study aimed to elucidate this phenomenon in Arabidopsis thaliana, to further understand the role of small HSPs (sHSPs) in heavy metal resistance in plants. Under Cu stress, transgenic A. thaliana expressing OsMSR3 showed higher tolerance to Cu, longer roots, higher survival rates, biomass, and relative water content, and accumulated more Cu, abscisic acid (ABA), hydrogen peroxide, chlorophyll, carotenoid, superoxide dismutase, and peroxidase than wild-type plants did. Moreover, OsMSR3 expression in A. thaliana increased the expression of antioxidant-related and ABA-responsive genes. Collectively, our findings suggest that OsMSR3 played an important role in regulating Cu tolerance in plants and improved their tolerance to Cu stress through enhanced activation of antioxidative defense mechanisms and positive regulation of ABA-responsive gene expression.

10.
Sci Total Environ ; : 135884, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31818573

RESUMO

Microbial communities play a key role in maintaining agroecosystem functioning and sustainability, but their response to excessive animal manure application and relevant mechanisms have not been thoroughly elucidated to date. This study investigated the responses of soil bacterial and fungal communities to pig manure (PM) amendment in red paddy soils. High-throughput sequencing revealed that PM amendment significantly reduced the relative abundance of Acidobacteria yet increased that of Bacteroidetes, Ignavibacteriae, Firmicutes, and Rozellomycota. The Cu and available phosphorus were the primary impact factors influencing bacterial and fungal diversity, respectively. Bacterial alpha-diversity tended to sharply decrease when the content of soil Cu was >30.70 mg kg-1, while fungal alpha-diversity did not continuously increase when the content of soil available phosphorus was >82.84 mg kg-1. Bacterial communities with a wider niche breadth showed significantly lower structural variation, whereas fungal communities with a narrower niche breadth showed greater variation in community structure. Soil heavy metals, primarily Cu and Zn, were the primary factors that affected bacterial communities, whereas soil fungal communities were mainly influenced by soil phosphorus. Bacterial and fungal communities showed distinct co-occurrence patterns, with bacterial communities showing a higher degree, a clustering coefficient, and betweenness centrality, but a lower closeness centrality. The findings highlighted that bacteria and fungi responded differently to PM amendment because of their discrepant niche breadth, interspecific relationships, and different tolerance to heavy metal and soil nutrient.

11.
Neuron ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31786011

RESUMO

How adult neurons coordinate lipid metabolism to regenerate axons remains elusive. We found that depleting neuronal lipin1, a key enzyme controlling the balanced synthesis of glycerolipids through the glycerol phosphate pathway, enhanced axon regeneration after optic nerve injury. Axotomy elevated lipin1 in retinal ganglion cells, which contributed to regeneration failure in the CNS by favorably producing triglyceride (TG) storage lipids rather than phospholipid (PL) membrane lipids in neurons. Regrowth induced by lipin1 depletion required TG hydrolysis and PL synthesis. Decreasing TG synthesis by deleting neuronal diglyceride acyltransferases (DGATs) and enhancing PL synthesis through the Kennedy pathway promoted axon regeneration. In addition, peripheral neurons adopted this mechanism for their spontaneous axon regeneration. Our study reveals a critical role of lipin1 and DGATs as intrinsic regulators of glycerolipid metabolism in neurons and indicates that directing neuronal lipid synthesis away from TG synthesis and toward PL synthesis may promote axon regeneration.

12.
J Comput Phys ; 386: 248-263, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787778

RESUMO

The combination of fluid-structure interactions with stochasticity, due to thermal fluctuations, remains a challenging problem in computational fluid dynamics. We develop an efficient scheme based on the stochastic immersed boundary method, Stokeslets, and multiple timestepping. We test our method for spherical particles and filaments under purely thermal and deterministic forces and find good agreement with theoretical predictions for Brownian Motion of a particle and equilibrium thermal undulations of a semi-flexible filament. As an initial application, we simulate bio-filaments with the properties of F-actin. We specifically study the average time for two nearby parallel filaments to bundle together. Interestingly, we find a two-fold acceleration in this time between simulations that account for long-range hydrodynamics compared to those that do not, suggesting that our method will reveal significant hydrodynamic effects in biological phenomena.

13.
Oncol Rep ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31789411

RESUMO

Nicotinic acetylcholine receptor (nAChR) subunit α5 (α5­nAChR) is involved in tumor cell proliferation, inhibition of apoptosis, progression of metastasis, and induction of angiogenesis in certain solid tumors. However, the role of α5­nAChR in prostate cancer cell growth and metastasis is unclear. In the present study, the role of α5­nAChR in cell proliferation, migration, invasion and apoptosis was investigated by silencing the expression levels of α5­nAChR in the prostate cancer cell lines DU145 and PC3. A siRNA oligonucleotide targeting α5­nAChR was designed. The cell proliferation of DU145 and PC3 cell lines was analyzed by the Cell Counting Kit­8 (CCK­8) assay. Cell migratory and invasive activities were determined using wound healing and Transwell assays, respectively. Western blot analysis was used to quantify α5­nAChR, p­AKT and p­ERK1/2 levels in DU145 and PC3 cells. Knockdown of α5­nAChR was associated with decreased cell proliferation, migration, invasion and increased apoptosis. In addition, decreased phosphorylation levels of AKT and ERK1/2 were revealed following α5­nAChR knockdown in DU145 and PC3 cells compared with those observed in the scramble control samples. The expression levels of the apoptosis­related proteins were altered following silencing of α5­nAChR. In summary, the data indicated that α5­nAChR was involved in the proliferation and invasion of human prostate cancer cells.

14.
ACS Nano ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789497

RESUMO

Structural asymmetry of materials plays a crucial role in developing multipurpose devices. Layered metallic transition metal dichalcogenides (MTMDCs) have been proposed as promising materials in electronics. However, they are still subject to native surface oxidation, limiting their practical applications. Combination of surface protection and native surface oxidation of MTMDCs will create asymmetric structures for devices but has yet to be explored. Here, we report a bifunctional NbS2-based vertical heterostructure derived from epitaxially grown NbS2 on MoS2 followed by a natural oxidation (MoS2-NbS2-NbOx), which simultaneously exhibits both high-efficiency tunneling conductive and memristive surfaces. With the tunneling conductive surface, the heterostructure functions as nearly ohmic contact electrodes with a two-dimensional (2D) channel in lateral transistors, delivering an enhanced mobility ∼140 times higher than that of the exfoliated NbS2-contacted device. With the memristive surface, the heterostructure can be used to build high-performance lateral or vertical memristors with low working voltages and synaptic functions. By combining both types of surfaces, a memristor array for nonvolatile memory is further developed. Moreover, the memristors show a good endurance for 2000 cycles of bending as flexible devices. The bifunctional heterostructure based on NbS2 offers a strategy toward the future applications of layered metallic materials.

15.
Gene ; : 144275, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31809843

RESUMO

Major latex protein/ripening-related proteins (MLP/RRP) subfamily are a class of proteins that play crucial roles in response to defense and stress response. However, their biological function is still not clear, the identification and characterization will provide essential information for understanding their roles. Here, we carried out a genome-wide evolutionary characteristics and gene expression analysis of the MLP family in apple (Malus domestica, Borkh.). A total of 36 MdMLP genes were screened in apple genome. They were uneven located on 5 chromosomes, where were mainly arranged in tandem clusters, and the phylogenetic analysis put forward further views on the evolutionary relationship and putative functions among the genes. The conserved motifs showed that the MLP proteins which contained motif 1 had the potential function, and tissue-specific expression analysis showed that apple MLP members had diverse biological roles. Furthermore, the results showed seven of the MdMLPs that harbored cis-acting regulatory elements in response to defense and stress, and our expression data proved that they were involved in biotic stresses. The present study provides new views to the evolution and regulation of MdMLP genes, which represent objectives of future research and incorporate in resistance-related molecular breeding projects.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31873970

RESUMO

Typical proteins for the formation of light weight and mechanically strong biological fibers are composed of folded rigid and un-folded flexible units. In stark contrast to fibrous proteins, globular proteins are generally not regarded as a good candidate for fiber production due to their intrinsic structure defects. Thus, it is challenging to develop an efficient strategy for the construction of mechanically strong fibers by spherical proteins. Here, we demonstrate a new type of robust protein fiber by microfluidic technique, in which globular bovine serum albumin (BSA) is spun efficiently. Remarkably, the toughness of the fibers was up to 143 MJ/m 3 , and after post-stretching treatment, their breaking strength increased almost to 300 MPa due to the induced long-range ordered structure in the fibers. The performance is comparable or even higher than that of many recombinant spider silks or regenerated silkworm fibers. Thus, this work opens a new way for making biological fibers with high performance.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31874219

RESUMO

Acute pancreatitis (AP) has been recognized as an uncommon yet potentially lethal complication following hematopoietic stem cell transplantation. This retrospective, nested, case-control study reviewed data from 5284 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2009 and 2018 at a single center, identifying 40 patients (0.76%) with AP following allo-HSCT. The diagnosis and severity of AP were established and classified according to the existing criteria. Younger age (P = .008), grade II-IV aGVHD (P = .010), a history of DLI (P = .033) and pre-existing gallstones (P = .003) are independent risk factors of AP after allo-HSCT. Post-transplant AP had a trend to negatively influence overall survival (OS) and nonrelapse mortality (NRM) (P = .063) for allo-HSCT recipients, but no significant difference was found. Patients with moderately severe and severe AP had significantly lower OS (P =.002) and higher NRM (P = .000) than other patients. Based on these findings, a risk score model is also established to predict the occurrence of AP. Our risk score model performed well in terms of discrimination when applied to the derivation samples. The patients were classified into a low-risk group (0-1 point), a medium-risk group (2-3 points) and a high-risk group (4 points or more). Significant difference was observed in AP incidence among the 3 groups. The predictive tool explored by our study might contribute to target high-risk patients and guide personalized AP prevention in allo-HSCT recipients.

18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(6): 916-923, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31875364

RESUMO

The clinical manifestations of patients with schizophrenia and patients with depression not only have a certain similarity, but also change with the patient's mood, and thus lead to misdiagnosis in clinical diagnosis. Electroencephalogram (EEG) analysis provides an important reference and objective basis for accurate differentiation and diagnosis between patients with schizophrenia and patients with depression. In order to solve the problem of misdiagnosis between patients with schizophrenia and patients with depression, and to improve the accuracy of the classification and diagnosis of these two diseases, in this study we extracted the resting-state EEG features from 100 patients with depression and 100 patients with schizophrenia, including information entropy, sample entropy and approximate entropy, statistical properties feature and relative power spectral density (rPSD) of each EEG rhythm (δ, θ, α, ß). Then feature vectors were formed to classify these two types of patients using the support vector machine (SVM) and the naive Bayes (NB) classifier. Experimental results indicate that: ① The rPSD feature vector P performs the best in classification, achieving an average accuracy of 84.2% and a highest accuracy of 86.3%; ② The accuracy of SVM is obviously better than that of NB; ③ For the rPSD of each rhythm, the ß rhythm performs the best with the highest accuracy of 76%; ④ Electrodes with large feature weight are mainly concentrated in the frontal lobe and parietal lobe. The results of this study indicate that the rPSD feature vector P in conjunction with SVM can effectively distinguish depression and schizophrenia, and can also play an auxiliary role in the relevant clinical diagnosis.

19.
Medicine (Baltimore) ; 98(52): e18566, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876759

RESUMO

OBJECTIVES: Helicobacter pylori (Hp) is an identified carcinogenic pathogen of human gastric cancer. China is not only one of the countries with high incidence and mortality of gastric cancer, but also a high infection area of Hp. As a multi-ethnic country, China may have a diverse prevalence of Hp infection among ethnics. This meta-analysis tends to compare the prevalence of Hp infection between Tibetan and Han ethnics, the results may provide evidence for targeted screening and eradication of Hp in China. METHODS: The following databases will be searched: PubMed, Web of Science, Technology Periodical Database (VIP), China National Knowledge infrastructure (CNKI), and WanFang databases. Studies which reported the prevalence of Hp infection between Tibetans and Hans in China are eligible. Two reviewers will independently screen studies, extract data and assess the risk of bias of included studies. The prevalence of Hp infection between Tibetan and Han ethnics will be compared by meta-analysis. Heterogeneity tests and meta-analyses will be conducted using RevMan 5.3 and Stata 12.0 softwares. Meanwhile, subgroup analysis, publication bias and sensitivity analysis evaluation will be performed where applicable. RESULTS: This study will be reported in compliance with the PRISMA statement.This systematic review will not be submitted for any ethical approval since no privacy health information will be included. The findings will be published through peer-reviewed publications or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42019121192. CONCLUSIONS: Our study will provide us evidence for tailored strategy and robustness of Hp screening and eradication among Tibetans.

20.
Blood Adv ; 3(24): 4312-4325, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31869417

RESUMO

The rate and extent of natural killer (NK)-cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand. NK-cell responsiveness was tuned commensurate with the number of inhibitory receptors from the donor. When both donor and host expressed the 3 major KIR ligands (HLA-C1, HLA-C2, and HLA-Bw4), NK cells expressing 3 inhibitory receptors (KIR2DL1/2DL3/3DL1) reached the maximum responsiveness against K562 cells compared with those NK cells expressing only 1 or 2 inhibitory receptors. When donor and host HLA both expressed all ligands for donor inhibitory KIRs, patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) showed the lowest recurrence rate after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In conclusion, this study demonstrates that when both donors and hosts present all the KIR ligands for donor KIRs, reconstituted NK cells achieve better functional education and contribute to least relapse among patients. This observation study was registered at www.clinicaltrials.gov as #NCT02978274.

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