An integrated interval-valued intuitionistic fuzzy technique for resumption risk assessment amid COVID-19 prevention.

Currently, China has achieved a remarkable achievement on the containment of COVID-19, which creates a favorable condition for the gradual resumption of normal life. However, COVID-19 infections continue to rise in many nations and some sporadic cases occur from time to time in China, which still poses some risks to the resumption. Hence, it is imperative to develop some reasonable techniques to assess the resumption risk. This paper aims to investigate an integrated interval-valued intuitionistic fuzzy (IVIF) technique to adroitly assess the resumption risk based on DEMATEL (decision making trial and evaluation laboratory), BWM (best-worst method) and SPA (set pair analysis). This integrated technique is called IVIF-DBWM-SPA, where the IVIF-DBWM (combined by the IVIF-DEMATEL and IVIF-BWM) is used to determine the global criteria weights and the IVIF-SPA is employed to generate the ranking order of the alternatives. The IVIF-DEMATEL and IVIF-BWM are used to determine the weights of dimensions and the weights of criteria under each dimension, respectively. In this IVIF-BWM, two bi-objective programming models are constructed by regarding experts' pessimistic and optimistic attitudes, respectively. Combined experts' intrapersonal and interpersonal uncertainties simultaneously, a bi-objective programming model is proposed to derive the dynamic weights of experts. Based on the determined weights of experts and criteria, an IVIF-SPA is developed to assess the risk levels of all alternatives. The validity of the proposed technique is demonstrated with a real case of college resumption risk assessment amid COVID-19. Some sensitivity and comparison analyses are provided to show the merits of the proposed technique.

[Effect of Acute Myeloid Leukemia Cells on the Proliferation and Apoptosis of Bone Marrow-Derived Mesenchymal Stromal Cells].

OBJECTIVE: To investigate the effect of acute myeloid leukemia cells in leukemia-microenvironment on proliferation and apoptosis of bone marrow-derived mesenchymal stromal cells (BM-MSC). METHODS: Acute myeloid leukemia (AML) murine models overexpressing MLL-AF9 were established. The number of BM-MSC of wild type (WT) and AML-derived mice were analyzed by flow cytometry. Morphology and growth differences between WT and AML-derived BM-MSC were analyzed by inverted fluorescence microscope. Proliferation and apoptosis of BM-MSC between these two groups were detected by Brdu and Annexin V/PI. RESULTS: Compared with WT-derived BM-MSC, the number and proliferation rate of AML-derived BM-MSC significantly increased (P<0.01, P<0.001), while apoptosis rate decreased (P<0.05). When cultured in vitro, BM-MSC grew faster under conditional medium. CONCLUSION: AML cells can promote proliferation and inhibit apoptosis of BM-MSC.

[Research Advances on the Role of Bone Marrow Stromal Cell in Acute Lymphoblastic Leukemia --Review].

Acute lymphoblastic leukemia (ALL) is a kind of the most common hematopoietic malignancy, its recurrence and drug resistance are closely related to the bone marrow microenvironment. Bone marrow stromal cell (BMSC) is an important part of the bone marrow microenvironment and their interaction with leukemia cells cannot be ignored. BMSC participates in and regulate signaling pathways related to proliferation or apoptosis of ALL cells by secretes cytokines or extracellular matrix proteins, thus affecting the survival of ALL cells. In this review, the research advance of several signaling pathways of the interaction between BMSC and ALL cells was summarized briefly.

An efficiency-based interval type-2 fuzzy multi-criteria group decision making for makeshift hospital selection.

Since makeshift hospitals have strong ability in blocking the spread of the virus, how to design some methods to select the reasonable sites of makeshift hospitals is vitally important for containing COVID-19. This paper investigates an efficiency-based multi-criteria group decision making (MCGDM) method by combining the best-worst method (BWM) and data envelopment analysis (DEA) in trapezoidal interval type-2 fuzzy (TrIT2F) environment. This MCGDM method is called TrIT2F-BWM-DEA, where the TrIT2F-BWM is used to determine the weights of criteria and decision-makers, and the TrIT2F-DEA is employed to rank alternatives by measuring their overall efficiencies. Based on cut set theory, the expectation and average expectation (AE) of TrIT2FSs are successively defined. To solve three key issues in the development of the TrIT2F-BWM, this paper proposes a flexible ranking relation of TrIT2FSs to transform the TrIT2F constraints, initiates an efficient theorem to normalize the TrIT2F weights, and designs an input-based consistency ratio to check the reliability of the determined weights. A fully TrIT2F-DEA model is originally built to measure the TrIT2F efficiencies of alternatives. The alternatives are finally ranked according to the AEs of alternatives' TrIT2F efficiencies. A site selection case of Fangcang hospitals and some comparative analyses are provided to confirm the validity and merits of the proposed TrIT2F-BWM-DEA.

Whole-genome sequence analysis unveils different origins of European and Asiatic mouflon and domestication-related genes in sheep.

The domestication and subsequent development of sheep are crucial events in the history of human civilization and the agricultural revolution. However, the impact of interspecific introgression on the genomic regions under domestication and subsequent selection remains unclear. Here, we analyze the whole genomes of domestic sheep and their wild relative species. We found introgression from wild sheep such as the snow sheep and its American relatives (bighorn and thinhorn sheep) into urial, Asiatic and European mouflons. We observed independent events of adaptive introgression from wild sheep into the Asiatic and European mouflons, as well as shared introgressed regions from both snow sheep and argali into Asiatic mouflon before or during the domestication process. We revealed European mouflons might arise through hybridization events between a now extinct sheep in Europe and feral domesticated sheep around 6000-5000 years BP. We also unveiled later introgressions from wild sheep to their sympatric domestic sheep after domestication. Several of the introgression events contain loci with candidate domestication genes (e.g., PAPPA2, NR6A1, SH3GL3, RFX3 and CAMK4), associated with morphological, immune, reproduction or production traits (wool/meat/milk). We also detected introgression events that introduced genes related to nervous response (NEURL1), neurogenesis (PRUNE2), hearing ability (USH2A), and placental viability (PAG11 and PAG3) into domestic sheep and their ancestral wild species from other wild species.

Antibody-powered DNA switches to initiate the hybridization chain reaction for the amplified fluorescence immunoassay.

Designing antibody-powered DNA nanodevice switches is crucial and fascinating to perform a variety of functions in response to specific antibodies as regulatory inputs, achieving highly sensitive detection by integration with simple amplified methods. In this work, we report a unique DNA-based conformational switch, powered by a targeted anti-digoxin mouse monoclonal antibody (anti-Dig) as a model, to rationally initiate the hybridization chain reaction (HCR) for enzyme-free signal amplification. As a proof-of-concept, both a fluorophore Cy3-labeled reporter hairpin (RH) in the 3' terminus and a single-stranded helper DNA (HS) were individually hybridized with a recognition single-stranded DNA (RS) modified with Dig hapten, while the unpaired loop of RH was hybridized with the exposed 3'-toehold of HS, isothermally self-assembling an intermediate metastable DNA structure. The introduction of target anti-Dig drove the concurrent conjugation with two tethered Dig haptens, powering the directional switch of this DNA structure into a stable conformation. In this case, the unlocked 3'-stem of RH was implemented to unfold the 5'-stem of the BHQ-2-labeled quench hairpin (QH), rationally initiating the HCR between them by the overlapping complementary hybridization. As a result, numerous pairs of Cy3 and BHQ-2 in the formed long double helix were located in spatial proximity. In response to this, the significant quenching of the fluorescence intensity of Cy3 by BHQ-2 was dependent on the variable concentration of anti-Dig, achieving a highly sensitive quantification down to the picomolar level based on a simplified protocol integrated with enzyme-free amplification.

Genome-Wide Detection of Copy Number Variations and Their Association With Distinct Phenotypes in the World's Sheep.

Copy number variations (CNVs) are a major source of structural variation in mammalian genomes. Here, we characterized the genome-wide CNV in 2059 sheep from 67 populations all over the world using the Ovine Infinium HD (600K) SNP BeadChip. We tested their associations with distinct phenotypic traits by conducting multiple independent genome-wide tests. In total, we detected 7547 unique CNVs and 18,152 CNV events in 1217 non-redundant CNV regions (CNVRs), covering 245 Mb (∼10%) of the whole sheep genome. We identified seven CNVRs with frequencies correlating to geographical origins and 107 CNVRs overlapping 53 known quantitative trait loci (QTLs). Gene ontology and pathway enrichment analyses of CNV-overlapping genes revealed their common involvement in energy metabolism, endocrine regulation, nervous system development, cell proliferation, immune, and reproduction. For the phenotypic traits, we detected significantly associated (adjusted P < 0.05) CNVRs harboring functional candidate genes, such as SBNO2 for polycerate; PPP1R11 and GABBR1 for tail weight; AKT1 for supernumerary nipple; CSRP1, WNT7B, HMX1, and FGFR3 for ear size; and NOS3 and FILIP1 in Wadi sheep; SNRPD3, KHDRBS2, and SDCCAG3 in Hu sheep; NOS3, BMP1, and SLC19A1 in Icelandic; CDK2 in Finnsheep; MICA in Romanov; and REEP4 in Texel sheep for litter size. These CNVs and associated genes are important markers for molecular breeding of sheep and other livestock species.

[Clinical Analysis of B-Cell Non-Hodgkin Lymphoma Treated with Modified Conditioning Regimen].

OBJECTIVE: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma. METHODS: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis. RESULTS: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis. CONCLUSION: The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.

Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep.

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

[Reaserch Advances in Immunotherapy for Acute Myeloid Leukemia--Review].

Acute myeloid leukemia (AML) is a malignant tumor with abnormal myelocyte differentiation. With the development of immunological technology, great importance has been attached to the immunotherapy of AML patients, which may become an effective treatment strategy for AML, and providing a new means for the prognosis and survival. In this review, the advanced research of immunotherapy for AML, such as antibody-dependent drugs, chimeric antigen receptor T cell therapy, and checkpoint inhibitors, the bastest reaserch advanves of clinical experiment for immunotherapy was summarized briefly.

Paternal Origins and Migratory Episodes of Domestic Sheep.

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.

System Prediction and Validation of TCM for Chronic Myeloid Leukemia Treatment from the Perspective of Low-Toxicity Chemotherapy: A Stilbene α-Viniferin Has a Proapoptotic Effect on K562 Cells via the Mitochondrial Pathway.

OBJECTIVE: In traditional Chinese medicine (TCM), chronic myeloid leukemia (CML) has been attributed to "poisoned bone marrow," which is viewed as a loss of Qi or blood, a deficiency in Yin or Yang that causes a complex imbalance between cell growth and death. Malignant myeloid progenitor cells display excessive growth that is difficult to control without toxicity. More than 60 herbs in TCM have shown efficacy against CML. However, the key molecules and mechanisms involved in the holistic-level characterization, as well as the effective target associations, are still unknown. METHODS: The present study employed a computational approach with filtering potential compounds via admetSAR, systems biology-based functional data prediction, and biochemical and molecular biological validation. RESULTS: We generated 118 bioactive compounds from 11 herbs within four dialectical therapy groups that are most commonly used to treat CML and predicted 141 potential targets. The stilbene resveratrol and its derivatives were found to be highly related to these targets. Among them, α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. In vitro, experimental data showed a nonnecrotic growth limitation of K562 cells caused by α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. µg·mL-1 at 24 h. Finally, we validated the chemotherapeutic effect of α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. CONCLUSIONS: Our work sheds light on the mechanism of the efficacy of the stilbene α-viniferin in TCM for the prevention of CML. This work also predicts and validates targets in the mitochondrial signaling pathway, providing a novel strategy for CML treatment.α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies.

The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury.

Oxidative stress is an important mechanism in acute lung injury (ALI) induced by paraquat (PQ), one of the most widely used herbicides in developing countries. In clinical prophylaxis and treatment, licorice is a widely used herbal medicine in China due to its strong alexipharmic characteristics. However, the corresponding biochemical mechanism of antioxidation and detoxification enzymes induced by licorice's ingredients is still not fully demonstrated. In this study, the detoxification effect of licorice was evaluated in vivo and in vitro. The detoxification and antioxidation effect of its active ingredients involved in the treatment was screened systematically according to Absorption, Distribution, Metabolism, and Excretion (ADME): predictions and evidence-based literature mining methods in silico approach. Data shows that licorice alleviate pulmonary edema and fibrosis, decrease Malondialdehyde (MDA) contents and increase Superoxide Dismutase (SOD) activity in PQ-induced ALI mice, protect the morphologic appearance of lung tissues, induce cytochrome 3A4 (CYA3A4) and Nuclear factor erythroid 2-related factor 2 (Nrf2) expression to active detoxification pathways, reduce the accumulation of PQ in vivo, protect or improve the liver and renal function of mice, and increase the survival rate. The 104 genes of PPI network contained all targets of licorice ingredients and PQ, which displayed the two redox regulatory enzymatic group modules cytochrome P450 (CYP450) and Nrf2 via a score-related graphic theoretic clustering algorithm in silico. According to ADME properties, glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A were employed due to their oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.1, and being highly associated with CYP450 and Nrf2 pathways, as potential activators to halt PQ-induced cells death in vitro. Both 3A4 inhibitor and silenced Nrf2 gene decreased the alexipharmic effects of those ingredients significantly. All these disclosed the detoxification and antioxidation effects of licorice on acute lung injury induced by PQ, and glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A upregulated CYP450 and Nrf2 pathways underlying the alexipharmic mechanisms of licorice.

Comparative mRNA and miRNA expression in European mouflon (Ovis musimon) and sheep (Ovis aries) provides novel insights into the genetic mechanisms for female reproductive success.

Prolific breeds of domestic sheep (Ovis aries) are important genetic resources due to their reproductive performance, which is characterized by multiple lambs per birth and out-of-season breeding. However, the lack of a comprehensive understanding of the genetic mechanisms underlying the important reproductive traits, particularly from the evolutionary genomics perspective, has impeded the efficient advancement of sheep breeding. Here, for the first time, by performing RNA-sequencing we built a de novo transcriptome assembly of ovarian and endometrial tissues in European mouflon (Ovis musimon) and performed an mRNA-miRNA integrated expression profiling analysis of the wild species and a highly prolific domestic sheep breed, the Finnsheep. We identified several novel genes with differentially expressed mRNAs (e.g., EREG, INHBA, SPP1, AMH, TDRD5, and ZP2) between the wild and domestic sheep, which are functionally involved in oocyte and follicle development and fertilization, and are significantly (adjusted P-value < 0.05) enriched in the Gene Ontology (GO) terms of various reproductive process, including the regulation of fertilization, oogenesis, ovarian follicle development, and sperm-egg recognition. Additionally, we characterized 58 differentially expressed miRNAs and 210 associated target genes that are essential for the regulation of female reproduction cycles through specific regulatory networks [e.g., (miR-136, miR-374a, miR-9-5p)-(EREG, INHBA)]. Furthermore, our integrated mRNA and miRNA expression profiling analysis elucidated novel direct and indirect miRNA/mRNA causal regulatory relationships related to the reproductive traits of the Ovis species. This study provides in-depth insights into the genomic evolution underlying the reproductive traits of the Ovis species and valuable resources for ovine genomics.

Contrasting Patterns of Genomic Diversity Reveal Accelerated Genetic Drift but Reduced Directional Selection on X-Chromosome in Wild and Domestic Sheep Species.

Analyses of genomic diversity along the X chromosome and of its correlation with autosomal diversity can facilitate understanding of evolutionary forces in shaping sex-linked genomic architecture. Strong selective sweeps and accelerated genetic drift on the X-chromosome have been inferred in primates and other model species, but no such insight has yet been gained in domestic animals compared with their wild relatives. Here, we analyzed X-chromosome variability in a large ovine data set, including a BeadChip array for 943 ewes from the world's sheep populations and 110 whole genomes of wild and domestic sheep. Analyzing whole-genome sequences, we observed a substantially reduced X-to-autosome diversity ratio (∼0.6) compared with the value expected under a neutral model (0.75). In particular, one large X-linked segment (43.05-79.25 Mb) was found to show extremely low diversity, most likely due to a high density of coding genes, featuring highly conserved regions. In general, we observed higher nucleotide diversity on the autosomes, but a flat diversity gradient in X-linked segments, as a function of increasing distance from the nearest genes, leading to a decreased X: autosome (X/A) diversity ratio and contrasting to the positive correlation detected in primates and other model animals. Our evidence suggests that accelerated genetic drift but reduced directional selection on X chromosome, as well as sex-biased demographic events, explain low X-chromosome diversity in sheep species. The distinct patterns of X-linked and X/A diversity we observed between Middle Eastern and non-Middle Eastern sheep populations can be explained by multiple migrations, selection, and admixture during the domestic sheep's recent postdomestication demographic expansion, coupled with natural selection for adaptation to new environments. In addition, we identify important novel genes involved in abnormal behavioral phenotypes, metabolism, and immunity, under selection on the sheep X-chromosome.

A genome-wide association study identifies a genomic region for the polycerate phenotype in sheep (Ovis aries).

Horns are a cranial appendage found exclusively in Bovidae, and play important roles in accessing resources and mates. In sheep (Ovies aries), horns vary from polled to six-horned, and human have been selecting polled animals in farming and breeding. Here, we conducted a genome-wide association study on 24 two-horned versus 22 four-horned phenotypes in a native Chinese breed of Sishui Fur sheep. Together with linkage disequilibrium (LD) analyses and haplotype-based association tests, we identified a genomic region comprising 132.0-133.1 Mb on chromosome 2 that contained the top 10 SNPs (including 4 significant SNPs) and 5 most significant haplotypes associated with the polycerate phenotype. In humans and mice, this genomic region contains the HOXD gene cluster and adjacent functional genes EVX2 and KIAA1715, which have a close association with the formation of limbs and genital buds. Our results provide new insights into the genetic basis underlying variable numbers of horns and represent a new resource for use in sheep genetics and breeding.

[Application study on multicolor combinational probe coding real-time PCR in detection of foodborne pathogens].

OBJECTIVE: To investigate the detection limit of multicolor combinational probe coding real-time PCR (MCPC-PCR) in detection of Salmonella and Staphylococcus aureus suspended in the food samples, and to apply MCPC-PCR to detect the samples of food poisoning. METHODS: Series concentration of bacterium suspension (10(1) - 10(9) CFU/ml) was prepared by using 22 simulated samples including fresh meat and cakes and then MCPC-PCR was applied to detect Salmonella and Staphylococcus aureus in 22 samples. Enrichment broth of 101 frozen samples and 5 early patients' anal swabs in food poisoning cases were detected after the DNA samples were extracted. RESULTS: The limits of MCPC-PCR assay in detecting Salmonella and Staphylococcus aureus were about 10(2) copies/test; 101 frozen enrichment broth of samples in food poisoning cases were detected by MCPC-PCR assay, of 23 positive samples, 18 were confirmed by bacteriology techniques; 96 samples detected by MCPC-PCR and bacteriology techniques had the same results, and the coincidence rate was 95.05%. Anal swabs, collected from 5 of early patients in a food poisoning case gave a clue to be Vibrio parahaemolyticus by MCPC-PCR assay and then were perfectly consistent with bacteriology assay. CONCLUSION: As a method of high sensitivity and good specificity, MCPC-PCR assay can quickly and conveniently detect multiple pathogens existing in food samples, therefore we recommend it to be used in rapidly screening or simultaneous detection of food-borne diseases.