Application of DNA barcodes in the genetic diversity of hard ticks (Acari: Ixodidae) in Kazakhstan.

Forty-five tick species have been recorded in Kazakhstan. However, their genetic diversity and evolutionary relationships, particularly when compared to ticks in neighbouring countries, remain unclear. In the present study, 148 mitochondrial cytochrome c oxidase subunit I (COI) sequence data from our laboratory and NCBI (National Center for Biotechnology Information; https://www.ncbi.nlm.nih.gov/ ) data were used to address this knowledge gap. Phylogenetic analyses showed that i) Hyalomma anatolicum anatolicum (Koch, 1844) ticks from Jambyl Oblast (southeastern Kazakhstan) and Gansu Province (northwestern China) constituted a newly deviated clade; and ii) Dermacentor reticulatus (Fabricius, 1974) ticks from South Kazakhstan Oblast were closer to those in Romania and Turkey. The network diagram of haplotypes showed that i) the H-1 and H-2 haplotypes of Dermacentor marginatus (Sulzer, 1776) ticks from Zhetisu and Almaty were all newly evolved; and ii) the H-3 haplotypes of Haemaphysalis erinacei (Pavesi, 1884) from Almaty Oblast and Xinjiang Uygur Autonomous Region (northwestern China) were evolved from the H-1 haplotype from Italy. In the future, more COI data from different tick species, especially from Kazakhstan and neighbouring countries, should be employed in the field of tick DNA barcoding.

Knowledge Graph Alignment Under Scarce Supervision: A General Framework With Active Cross-View Contrastive Learning.

Over recent years, a number of knowledge graphs (KGs) have emerged. Nevertheless, a KG can never reach full completeness. A viable approach to increase the coverage of a KG is KG alignment (KGA). The majority of previous efforts merely focus on the matching between entities, while largely neglect relations. Besides, they heavily rely on labeled data, which are difficult to obtain in practice. To address these issues, in this work, we put forward a general framework to simultaneously align entities and relations under scarce supervision. Our proposal consists of two main components, relation-enhanced active instance selection (RAS), and cross-view contrastive learning (CCL). RAS aims to select the most valuable instances to be labeled with the guidance of relations, while CCL contrasts cross-view representations to augment scarce supervision signals. Our proposal is agnostic to the underlying entity and relation alignment models, and can be used to improve their performance under limited supervision. We conduct experiments on a wide range of popular KG pairs, and the results demonstrate that our proposed model and its components can consistently boost the alignment performance under scarce supervision.

Effect of Different Glucose Monitoring Methods on Bold Glucose Control: A Systematic Review and Meta-Analysis.

Objective: To evaluate the effectiveness of different glucose monitoring methods on blood glucose control and the incidence of adverse events among patients with type 1 diabetes mellitus. Methods: Using the method of literature review, the databases PubMed, Cochrane, and Embase were retrieved to obtain relevant research literature, and the selected studies were analyzed and evaluated. This study used Cochrane software RevMan5.4 to statistically analyze all the data. Results: A total of 15 studies were included in this study, including 10 randomized controlled trials and 5 crossover design trials, with a total of 2071 patients. Meta-analysis results showed that continuous blood glucose monitoring (CGM) could significantly reduce the HbA1c level of patients, weighted mean difference (WMD) = -2.69, 95% confidence interval (CI) (-4.25, -1.14), and P < 0.001 compared with self-monitoring of blood glucose (SMBG). Meanwhile, the incidence of severe hypoglycemia in the CGM group was significantly decreased, risk ratio (RR) = 0.52, 95% CI 0.35-0.77, and P = 0.001. However, there was no statistical difference in the probability of diabetic ketoacidosis between CGM and SMBG groups, RR = 1.34, 95% CI 0.57-3.15, and P = 0.5. Conclusion: Continuous blood glucose monitoring is associated with lower blood glucose levels than the traditional blood glucose self-test method.

Novel Streptococcus uberis sequence types causing bovine subclinical mastitis in Hainan, China.

AIM: To determine the molecular epidemiology, genotypes and phenotypes of the major species of Streptococcus associated with bovine subclinical mastitis in Hainan, China. METHODS AND RESULTS: In total, 150 subclinical mastitis milk samples were collected from two large dairy farms in Hainan. On the basis of biochemical tests and 16S rDNA sequencing, 39 samples were Streptococcus positive and the most frequently isolated species was Streptococcus uberis (n = 29, 74.4%). According to multilocus sequence typing (MLST), and assays of biofilm formation, antimicrobial susceptibility, resistance and virulence genes, the S. uberis isolates were clustered into nine new sequence types (STs; ST986-ST994) but were not merged into a clonal group (except for ST991 [CC143]). All isolates produced biofilm, but most weakly. The dominant virulence pattern was hasABC + sua + gapC + oppF + pauA + mtuA + cfu (27/29, 91.1%), based on the 11 virulence genes tested. The majority of isolates (88.46%) carried at least one resistance gene, and more than half (58.62%) were multidrug-resistant. The main resistance genes were linB (65.5%), ermB (37.9%) and tetS (34.5%), among the six antibiotic resistance genes and 11 antimicrobials tested. CONCLUSION: Environmental S. uberis is important in bovine subclinical mastitis in Hainan. SIGNIFICANCE AND IMPACT OF THE STUDY: Streptococcus uberis isolates in Hainan, China, show distinct MLST, virulence and antibiotic resistance characteristics.

A Retrospective Study on the Use of Chinese Patent Medicine in 24 Medical Institutions for COVID-19 in China.

Objective: This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20-22, February 16-18, March 01-03, April 01-03, 2020), and explore its contribution to combating the disease. Methods: 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ2 test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software. Results: 1) The heat-clearing medicine was the main use category nationwide during January 20-22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16-18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions (p < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01-03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01-03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01). Conclusion: Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation.

Association between a microRNA binding site polymorphism in SLCO1A2 and the risk of delayed methotrexate elimination in Chinese children with acute lymphoblastic leukemia.

Organic anion-transporting polypeptide 1A2 (OATP1A2) is involved in the cellular uptake of methotrexate (MTX). Genetic variation in solute carrier organic anion transporter family member 1A2 (SLCO1A2, the coding gene of OATP1A2) has important implications for the elimination of MTX. We investigated the association between a microRNA (miRNA) binding site polymorphism (rs4149009 G > A) in the 3'-untranslated region (3'-UTR) of SLCO1A2 with the serum MTX concentrations in Chinese children with acute lymphoblastic leukemia (ALL). Genotyping for SLCO1A2 rs4149009 G > A in 141 children with ALL was performed using the Sequenom MassARRAY system. Serum MTX concentrations were determined by fluorescence polarization immunoassay. The percentages of MTX level ≥1 µmol/L at 42 h were compared among the AA, GA, and GG genotypes. The minor allele frequency observed in this study (33.0%) was significantly lower than that in the African samples reported in the 1000 Genomes Project (57.4%, P = 0.00). The incidence rate of delayed MTX elimination was significantly higher in patients with the GG genotype (23.1%) compared with the AA genotype (0.0%, P = 0.03). Bioinformatics tools predicted that the rs4149009 A allele would disrupt the putative binding sites of hsa-miR-324-3p and hsa-miR-1913. These results indicate that the rs4149009 G > A polymorphism might affect MTX pharmacokinetics by interfering with the function of miRNAs.

Association between MTHFR microRNA binding site polymorphisms and methotrexate concentrations in Chinese pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: The pharmacokinetics and therapeutic response to methotrexate (MTX) display large variability in the treatment of acute lymphoblastic leukemia (ALL). The aim of the present study was to investigate the association of two microRNA (miRNA) binding site polymorphisms (rs3737966 G > A and rs35134728 DEL/TTC) in the 3'-untranslated region of MTHFR with serum MTX concentrations, in a Chinese pediatric population with ALL. METHODS: Genotyping for MTHFR rs3737966 and rs35134728 in 144 children with ALL was performed using the Sequenom MassArray system (Sequenom, San Diego, CA, USA). Serum MTX concentrations were measured by a fluorescence polarization immunoassay 24 h (C24h ) and 42 h (C42h ) after administration. The effects of the polymorphisms on concentration-to-dose (C/D) ratios of MTX were assessed. RESULTS: Complete linkage disequilibrium between rs3737966 and rs35134728 polymorphisms (r2  = 1) was found in the study population. The minor allele frequency observed in the present study (17.4%) was significantly lower than those in European and African samples reported in the 1000 Genomes Project (42.9% and 63.9%, respectively; p < 0.01). The C/D ratios of MTX at 24 and 42 h for the TTC/TTC-A/A haplotype carriers (11.74 and 0.07 µmol/l per g/m2 , respectively) were significantly lower than those in DEL/DEL-G/G or DEL/TTC-G/G haplotype carriers (12.49 and 0.09 µmol/l per g/m2 , respectively; p < 0.05). Computational predictions suggested that the two polymorphisms overlapped with putative binding sites of several miRNAs. CONCLUSIONS: The rs3737966 and rs35134728 polymorphisms in MTHFR were associated with serum MTX concentrations. The findings of the present study indicate that miRNAs might be involved in the post-transcriptional regulation of MTHFR.

Pygopus 2 promotes kidney cancer OS-RC-2 cells proliferation and invasion in vitro and in vivo.

OBJECTIVE: Human Pygopus 2 (Pygo2) was recently discovered to be a component of the Wnt signaling pathway required for ß-catenin/Tcf-mediated transcription. But the role of Pygo2 in malignant cell proliferation and invasion has not yet been determined. METHODS: Lentivirus-mediated small interfering RNA (siRNA) and vector-based overexpression were used to study the function of Pygo2 in OS-RC-2 cells. The resulted cells were subject to Western blotting assay, MTT assay, colony formation and cell invasion assays. Furthermore, renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells. Immunohistochemistry (IHC) staining of matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) was performed in tumor tissue. RESULTS: Pygo2 gene was successful knocked down and overexpressed in RCC OS-RC-2 cells by using an shRNA and overexpressing vector, respectively. Overexpression of Pygo2 effectively promoted cell proliferation, colony formation and invasion in vitro. Knockdown of Pygo2 obviously inhibited xenograft tumor growth in nude mice. In addition, overexpression of Pygo2 increased the levels of MMP-7, MMP-9 and VEGF in the xenograft tumors. CONCLUSION: Pygo2 has a role in promoting cell proliferation, invasion and metastasis, and may regulate angiogenesis via the Wnt/ß-catenin signaling pathway.

Simultaneous Determination of Nine Active Compounds of the Traditional Chinese Medicinal Prescription Shaoyao-Gancao-Tang and Analysis of the Relationship between Therapeutical Effect and Compatibility of Medicines.

A simple and sensitive HPLC-DAD detection method was established for the simultaneous determination of nine compounds including oxypaeoniflorin, albiflorin, paeoniflorin, benzoylpaeoniflorin, glycyrrhizic acid, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in the Traditional Chinese Medicinal Prescription Shaoyao-Gancao-Tang (SGT) and we analyze the relationship between therapeutical effect and compatibility of medicines by using an Agilent extend-C18 column at a flow rate of 1 mL/min. The column temperature was maintained at 30°C and the detection wavelength was set at 230 nm for oxypaeoniflorin, albiflorin, paeoniflorin, benzoylpaeoniflorin, and glycyrrhizic acid; 276 nm for liquiritin and liquiritigenin; 360 nm for isoliquiritin and isoliquiritigenin. The total contents of the nine compounds in SGT varied from 4.65 to 20.06 mg/mL. The results of this study showed that the content of chemical compounds of Traditional Chinese Medicinal Prescription is mainly influenced by the dosage and compatibility of medicines and the therapeutical effect of Traditional Chinese Medicinal prescription is mainly influenced by the dosage and compatibility of medicines. The method could be suitable for quality control of SGT with bioactive multicompounds.

Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia.

PURPOSE: To investigate the correlation between common genetic polymorphisms of folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), and methylenetetrahydrofolate reductase (MTHFR) and serum levels of methotrexate (MTX) in Chinese children with acute lymphoblastic leukemia (ALL). METHODS: Ninety-one children with ALL who received high-dose MTX were recruited. The polymorphisms FPGS (rs1544105 G>A), GGH (rs3758149 C>T), and MTHFR (rs1801133 C>T) were genotyped through polymerase chain reaction-restriction fragment length polymorphism analysis. Serum MTX was measured by fluorescence polarization immunoassay. The association between targeted polymorphisms and MTX concentration-to-dose (C/D) ratios was assessed, and between targeted polymorphisms and the percent of MTX above the therapeutic threshold (40 µmol/L). RESULTS: The minor allele frequencies of rs1544105 G (34.1%), rs3758149 T (19.2%), and rs1801133 C (48.4%) observed in our population were significantly lower than those reported for European populations (64.2, 30.8, and 69.0%, respectively). The association between the GGH rs3758149 polymorphism and MTX C/D was gender-specific; in girls, the MTX C/D at 24 h of GGH rs3758149 CC carriers (12.09 µmol/L per g/m(2)) was significantly lower than that of CT or TT carriers (16.80 µmol/L per g/m(2)). The percent of serum MTX above the therapeutic threshold in GGH rs3758149 CC carriers (18.3%) was significantly lower than that of CT and TT carriers (38.7%). The MTX C/D ratios at 24 h and the percent of MTX >40 µmol/L for the A-T-T (three variant alleles) haplotype were significantly higher than those for other haplotypes combined (P < 0.05). CONCLUSIONS: These data indicate that FPGS rs1544105, GGH rs3758149, and MTHFR rs1801133 polymorphisms contribute to the variability of MTX pharmacokinetics, and their genotyping may be useful to reduce toxicities associated with MTX therapy.

Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia.

MicroRNAs (miRNAs) are a class of short non-coding RNA that can specially bind to the 3'-untranslated region of target mRNAs and regulate gene expression at the posttranscriptional level. This study investigated the effects of a miRNA binding site polymorphism (rs1051296) in solute carrier family 19, member 1 (SLC19A1) on serum methotrexate (MTX) concentrations in Chinese children with acute lymphoblastic leukemia (ALL). Genotyping for SLC19A1 rs1051296 G>T in 131 children with ALL was performed using the Sequenom MassArray system. A total of 131 patients received high-dose MTX treatment, and serum MTX concentrations were measured by a fluorescence polarization immunoassay 24 (MTX C24h) and 42 h (MTX C42h) after administration. The frequency of the rs1051296 T allele observed in this study (46.2 %) was significantly lower than that previously observed in a European population (60.7 %, P = 0.002). There was significant association between rs1051296 G>T and MTX C24h (29.97, 32.34, and 39.01 µmol/L for GG, GT, and TT genotypes, respectively, P = 0.04). The percentage of patients with an MTX concentration above the therapeutic threshold (40 µmol/L) was significantly lower in GG carriers compared with that in GT and TT carriers (8.6 % for GG genotype vs. 26.8 and 40.0 % for CT and TT genotypes, respectively, P = 0.02). Delayed elimination of MTX (C42h > 1 µmol/L) was less frequent in GG carriers than in GT and TT carriers. Rs1051296 G>T was associated with MTX plasma concentration, suggesting that miRNAs might be involved in the post-transcriptional regulation of SLC19A1.