Comparative study on the quality control effectiveness of AI-PBRTQC and traditional PBRTQC model in identifying quality risks.

Introduction: We compared the quality control efficiency of artificial intelligence-patient-based real-time quality control (AI-PBRTQC) and traditional PBRTQC in laboratories to create favorable conditions for the broader application of PBRTQC in clinical laboratories. Materials and methods: In the present study, the data of patients with total thyroxine (TT4), anti-Müllerian hormone (AMH), alanine aminotransferase (ALT), total cholesterol (TC), urea, and albumin (ALB) over five months were categorized into two groups: AI-PBRTQC group and traditional PBRTQC group. The Box-Cox transformation method estimated truncation ranges in the conventional PBRTQC group. In contrast, in the AI-PBRTQC group, the PBRTQC software platform intelligently selected the truncation ranges. We developed various validation models by incorporating different weighting factors, denoted as λ. Error detection, false positive rate, false negative rate, average number of the patient sample until error detection, and area under the curve were employed to evaluate the optimal PBRTQC model in this study. This study provides evidence of the effectiveness of AI-PBRTQC in identifying quality risks by analyzing quality risk cases. Results: The optimal parameter setting scheme for PBRTQC is TT4 (78-186), λ = 0.03; AMH (0.02-2.96), λ = 0.02; ALT (10-25), λ = 0.02; TC (2.84-5.87), λ = 0.02; urea (3.5-6.6), λ = 0.02; ALB (43-52), λ = 0.05. Conclusions: The AI-PBRTQC group was more efficient in identifying quality risks than the conventional PBRTQC. AI-PBRTQC can also effectively identify quality risks in a small number of samples. AI-PBRTQC can be used to determine quality risks in both biochemistry and immunology analytes. AI-PBRTQC identifies quality risks such as reagent calibration, onboard time, and brand changes.

Associations between chronic obstructive pulmonary disease and ten common cancers: novel insights from Mendelian randomization analyses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. METHODS: We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. RESULTS: The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15-1.77, FDR = 6.37 × 10-3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03-2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7-26.1%), 36.1% (24.9-33.2%), 35.9% (25.7-34.9%), and 35.5% (26.2-34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. CONCLUSIONS: COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model.

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.

Assessment of patient based real-time quality control on comparative assays for common clinical analytes.

BACKGROUND: It is critical for laboratories to conduct multianalyzer comparisons as a part of daily routine work to strengthen the quality management of test systems. Here, we explored the application of patient-based real-time quality controls (PBRTQCs) on comparative assays to monitor the consistency among clinical laboratories. METHODS: The present study included 11 commonly tested analytes that were detected using three analyzers. PBRTQC procedures were set up with exponentially weighted moving average (EWMA) algorithms and evaluated using the AI-MA artificial intelligence platform. Comparative assays were carried out on serum samples, and patient data were collected. Patients were divided into total patient (TP), inpatient (IP), and outpatient (OP) groups. RESULTS: Optimal PBRTQC protocols were evaluated and selected with appropriate truncation limits and smoothing factors. Generally, similar comparative assay performance was achieved using both the EWMA and median methods. Good consistency between the results from patients' data and serum samples was obtained, and unacceptable bias was detected for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) when using analyzer C. Categorizing patients' data and applying specific groups for comparative assays could significantly improve the performance of PBRTQCs. When monitoring the inter- and intraanalyzer stability on a daily basis, EWMA was superior in detecting very small quality-related changes with lower false-positive alarms. CONCLUSIONS: We found that PBRTQCs have the potential to efficiently assess multianalyzer comparability. Laboratories should be aware of population variations concerning both analytes and analyzers to build more suitable PBRTQC protocols.

The Influences of COVID-19 on Patients With Chronic Kidney Disease: A Multicenter Cross-Sectional Study.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has attracted global attention. During the lockdown period of COVID-19, follow-up of many patients with chronic disease had been interrupted, which brought severe challenges to better management of their disease. This study aimed at exploring the change of illness, daily life, and psychological responses during the COVID-19 pandemic among chronic kidney disease (CKD) patients. Methods: A total of 612 patients were enrolled in this study; 282 patients were categorized into the CKD stage 1-2 group and 330 patients were categorized into the CKD stage 3-5 group. Among two groups, 168 (27.5%) and 177 (28.9%) patients were female with a median age of 42 and 45, respectively. The study was conducted by collecting the questionnaires in five nephrology centers. The questionnaire consisted of assessment of anxiety by using the Self-Rating Anxiety Scale and the influences of COVID-19, which included basic demographic data, the influences of COVID-19 on illness and daily life, as well as the patients' psychological responses during the epidemic. Results: A total of 612 patients were included and divided into two groups according to eGFR. Ninety-six patients (34%) in the CKD stage 1-2 group and 141 patients (42.7%) in the CKD stage 3-5 group had reduced their follow-up frequency (p = 0.031). More patients with CKD stages 1-2 consulted online (25.9%), p = 0.005. Besides, patients in the CKD stage 3-5 group tended to be more anxious about follow-up (p = 0.002), fearful of being infected with COVID-19 (p = 0.009), and more likely to feel symptoms getting worse (p = 0.006). The standard scores of SAS were 48.58 ± 7.082 and 51.19 ± 5.944 in the CKD stage 1-2 group and the CKD stage 3-5 group, respectively (p < 0.001). There were significant differences in the severity of anxiety (p = 0.004). Conclusion: COVID-19 had a greater impact on patients with CKD stages 3-5 than those with stages 1-2 in terms of illness, daily life, and psychological disorder. Patients with CKD stages 3-5 were more anxious during the COVID-19 pandemic.

Downregulating of hemB via synthetic antisense RNAs for improving 5-aminolevulinic acid production in Escherichia coli.

Aminolevulinic acid (ALA), a type of natural non-protein amino acid, is a key precursor for the biosynthesis of heme, and it has been broadly applied in medicine, agriculture. Several strategies have been applied to enhance ALA synthesis in bacteria. In the present study, we employed synthetic antisense RNAs (asRNAs) of hemB (encodes ALA dehydratase) to weaken metabolic flux of ALA to porphobilinogen (PBG), and investigated their effect on ALA accumulation. For this purpose, we designed and constructed vectors pET28a-hemA-asRNA and pRSFDuet-hemA-asRNA to simultaneously express 5-ALA synthase (ALAS, encoded by hemA) and PTasRNAs (2 inverted repeat DNA sequences sandwiched with the antisense sequence of hemB), selecting the region ranging from - 57 nt upstream to + 139 nt downstream of the start codon of hemB as a target. The qRT-PCR analysis showed that the mRNA levels of hemB were decreased above 50% of the control levels, suggesting that the anti-hemB asRNA was functioning appropriately. ALA accumulation in the hemB weakened strains were 17.6% higher than that obtained using the control strains while accumulating less PBG. These results indicated that asRNAs can be used as a tool for regulating ALA accumulation in E. coli. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02733-8.

A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy.

It was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan-Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074 .

Sex disparities in IgA nephropathy: a retrospective study in Chinese patients.

AIM: The aim of this study was to explore the effect of sex on the clinicopathological features and long-term outcomes of IgAN patients. METHODS: A total of 1096 adult IgAN patients were divided into male and female groups. Clinicopathological features and risk factors of IgAN patients of different genders were contrasted. The primary endpoint was the combined endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) and/or end stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or dialysis). The effect of gender on prognosis of IgAN was assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: In total, 475 male patients and 621 female patients were included in this study. At baseline, male patients had higher values for blood pressure, serum creatinine, urine protein and serum uric acid, as well as lower levels of eGFR. Further analysis indicated that tubular atrophy/interstitial fibrosis (T) lesions and vascular lesions were more frequent in male patients. During the follow-up period of 40.9 ± 24.2 months, kidney survival rates of male IgAN patients were remarkably lower than those of female patients. Using multivariate Cox regression analysis, male gender was identified as an independent risk factor for poor outcomes (ß = 0.384, Wald = 4.290, Exp (ß) = 1.47, p = 0.038), including hypertension, low eGFR, IgM deposition, arteriosclerosis lesions and T1-T2 lesions. However, male and female patients were characterized by different risk factors. CONCLUSION: Male patients presented with more severe clinical and pathological changes than female patients. Renal survival rates of male patients were remarkably lower than those of female patients, and male gender was identified as an independent risk factor for poor outcomes.

The expression of SARS-CoV-2 receptor ACE2 and CD147, and protease TMPRSS2 in human and mouse brain cells and mouse brain tissues.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been discovered as the pathogenic cause of the coronavirus disease 19 (COVID-19). Cellular entry of SARS-CoV-2 are mediated by the spike glycoprotein of virus, and the host specific receptors and proteases. Recently, besides pulmonary complications as the chief symptom, investigations have also revealed that SARS-CoV-2 can trigger neurological manifestations. Herein, to investigate the expression level of receptors and related proteases is important for understanding the neuropathy in COVID-19. We determined the expression levels of receptor ACE2 and CD147, and serine protease TMPRSS2 in human and mouse brain cell lines and mouse different region of brain tissues with qRT-PCR and Western blot. The results showed that the expression pattern of all them was very different to that of lung. ACE2 is lower but CD147 is higher expressed in mostly brain cell lines and mouse brain tissues comparing with lung cell line and tissue, and TMPRSS2 has consistent expression in brain cell lines and mouse lung tissues. It is suggested that SARS-CoV-2 might have a different way of infection to cerebral nervous system. Our finding will offer the clues to predict the possibility of SARS-CoV-2 infection to human brain nervous system and pathogenicity.

Comparative study on hemoglobin A1c, glycated albumin and glycosylated serum protein in aplastic anemia patients with Type 2 diabetes mellitus.

OBJECTIVE: To differentiate the value of hemoglobin A1c (HbA1c), glycated albumin (GA) and glycosylated serum protein (GSP) in monitoring blood glucose of patients with aplastic anemia. METHODS: 42 patients with aplastic anemia (AA) and 30 patients with AA and Type 2 diabetes mellitus (T2DM) were enrolled in the study, in comparison with 114 healthy subjects and 88 subjects with T2DM. HbA1c, GA, GSP, fasting plasma glucose (FPG), hemoglobin (Hb) and albumin (ALB) were measured, and group comparison and correlation analysis were carried out. RESULTS: Compared with the non-diabetes patients while ALB were <30 g/l or 30-40 g/l, the HbA1c and GSP values in AA, T2DM and AA+T2DM patients were significantly higher while the GA values were lower. Moreover, no differences in FPG levels. The AA+T2DM patients with ALB >40 g/l had higher HbA1c level, with no difference in GA, GSP and FPG levels. There was a positive correlation between HbA1c and GA in healthy group (ALB ≥ 40 g/l), AA patients (ALB 30-40 g/l and ≥40 g/l), T2DM patients (ALB 30-40 g/l and ≥40 g/l) and AA+T2DM patients (ALB 30-40 g/l and ≥40 g/l) but not in those with ALB < 30 g/l. CONCLUSION: The HbA1c results were affected by moderate-to-severe anemia, but not mild anemia. HbA1c is not recommended to detect blood glucose levels in AA patients (Hb < 90 g/l) or AA patients (ALB < 30 g/l). FPG and GSP are not suitable for AA patients.

Application of biological variation and six sigma models to evaluate analytical quality of six HbA1c analyzers and design quality control strategy.

Objective: To apply biological variation and six Sigma models to evaluate analysis performance of 6 HbA1c analyzers and design the new quality control strategy. Method: We collected data of imprecision and inaccuracy from routine internal quality control (June 2017-December 2017) and proficiency test of NGSP, respectively. The coefficient of variance (CV)% and bias% were plotted in the biological variation and six sigma models. The new quality control strategy was designed by the sigma value and OPSpecs. The quality improvement was guided by the QGI. Results: The analytical performance of 6 HbA1c analyzers in our laboratory were good in the routine model, However, 50% (3/6) and 67% (4/6) of the HbA1c analyzers reached the acceptable level in the biological variation and six Sigma model, respectively. We also design personalized control strategy and promote quality improvement by combining the sigma value, OPSpecs, and QGI. Conclusions: Biological variation model and six sigma model could visually display the performance of 6 HbA1c analyzers and personalized control strategy could be designed based on the sigma value, OPSpecs, and QGI.

CK1 inhibitor affects in vitro maturation and developmental competence of bovine oocytes.

The objectives of present study were to evaluate the effect of casein kinase 1 (CK1) inhibition D4476 on in vitro maturation (IVM) and developmental competence of bovine oocytes. The cumulus oocyte complexes (COCs) were cultured in maturation medium with D4476 (0, 2, 5, 10, 20 µM) for 24 hr. After IVM and in vitro fertilization, through expansion average scores of cumulus cells (CCs), oocyte maturation efficiency, cleavage rate and blastocyst rate of zygote, we found 5 µM D4476 could increase the development potential of oocytes. After the COCs were treated with 5 µM D4476, the results of quantitative real-time PCR analysis, Lichen red staining and PI staining showed that under without affecting germinal vesicle breakdown and nuclear morphology, D4476 could significantly decrease CK1 and upregulate TCF-4 in oocytes. Furthermore, without influencing the level of Bad and CTSB, D4476 could significantly increase the expression of ß-catenin, TCF-4, Cx43, MAPK, PTGS-2, PTX-3, TGS-6, Bax and Bcl-2 in CCs. Western blot analysis revealed that the addition of 5 µM D4476 during the maturation of COCs resulted in a lower level of Cx43 protein at 12 hr and a higher expression of Cx43 protein at 24 hr compared to the group without D4476. These results indicate that adding optimum D4476 (5 µM) to maturation medium is beneficial to maturity efficiency and development competence of bovine oocytes.

Biochemical characterization of acyl-coenzyme A synthetases involved in mycobacterial steroid side-chain catabolism and molecular design: synthesis of an anti-mycobacterial agent.

The metabolism of host cholesterol by Mycobacterium tuberculosis is an important factor for both its virulence and pathogenesis. However, the rationale for this cholesterol metabolism has not been fully understood yet. In the present study, we characterized several previously undescribed acyl-CoA synthetases that are involved in the steroid side-chain degradation in Mycobacterium smegmatis, and an analogue of intermediate from steroid degradation, 5'-O-(lithocholoyl sulfamoyl) adenosine (LCA-AMS), was successfully designed and synthesized to be used as a specific anti-mycobacterial agent. The acyl-CoA synthetases exhibited strong preferences for the length of side chain. FadD19 homologs, including FadD19 (MSMEG_5914), FadD19-2 (MSMEG_2241), and FadD19-4 (MSMEG_3687), are unanimously favorable cholesterol with a C8 alkanoate side chain. FadD17 (MSMEG_5908) and FadD1 (MSMEG_4952) showed high preferences for steroids, containing a C5 alkanoate side chain. FadD8 (MSMEG_1098) exhibited specific activity toward cholestenoate with a C8 alkanoate side chain. An acylsulfamoyl analogue of lithocholate, 5'-O-(lithocholoyl sulfamoyl) adenosine (LCA-AMS), was designed and synthesized. As expected, the intermediate analogue not only specifically inhibited those steroid-activated acyl-CoA synthetases, but also selectively inhibited the growth of mycobacterial species, including M. tuberculosis, M. smegmatis, and Mycobacterium neoaurum. Overall, our research advanced our understanding of mycobacterial steroid degradation and provided new insights to develop novel mechanism-based anti-mycobacterial agents.

False measurement of glycated hemoglobin in patients without hemoglobin A.

Background: Hemoglobin (Hb) A1c, a biochemical marker widely used in monitoring diabetes mellitus, can be quantitatively measured by various examining systems. However, significant errors still exist. In the present study, we evaluated the HbA1c level in five patients with compound heterozygotes by five different examining systems and our goal is to identify the existence of erroneous HbA1c measurement.Methods: Blood samples collected from normal (no hemoglobin variants) and abnormal (compound heterozygotes) patients were analyzed by capillary electrophoresis technique and sequence analysis. The samples without HbA expression via above methods were further analyzed for HbA1c by ion exchange HPLC Variant II/ Variant II Turbo 2.0 (VII and VII-T 2.0), boronate affinity HPLC, capillary electrophoresis, and Tinaquant immunoassay.Results: HbA1c expression were unexpectedly detected in the compound heterozygous samples by using additional examining systems: The HPLC VII and VII-T 2.0 detected HbA1c expression in two of five samples and failed to detect the abnormal HbA2 expression; the CE system detected HbA1c expression in one of five samples with abnormal HbA2 expression; the Ultra2 and PPI system detected the HbA1c expression of all samples without abnormal HbA2Conclusions: Five human samples without HbA expression were additionally detected with HbA1c expression with or without abnormal HbA2 expression by five analysis systems and the different examining assay potentially affected the test results. These results demonstrated that the limitations of current examining systems for monitoring patients with hemoglobin disorders highlighting the further improvement in the method of clinical HbA examination.

Elimination of typical polycyclic musks in a full-scale membrane bioreactor combined with anaerobic-anoxic-oxic process in municipal wastewater treatment plant.

The objective of this study was to investigate the removal of 11 synthetic polycyclic musks in a municipal wastewater treatment plant located in Jilin, China, by using a membrane bioreactor combined with anaerobic-anoxic-oxic process. The analysis of synthetic polycyclic musks was conducted with gas chromatography/mass spectrometry after solid-phase extraction. The removal efficiency of 11 synthetic polycyclic musks ranged from 65.9% (3-methylcyclopentadecanone) to 84.6% (Galoxolide) in the influent. Along the treatment process, it was observed that the anaerobic tank could remove the synthetic polycyclic musks effectively whereas the role of the membrane was to the musks, which could be ascribed to the relatively strong hydrophobic property of the musks. The sludge-water distribution coefficients (Kd values) as indicator of adsorption propensity for the sludge from anaerobic, anoxic, oxic and membrane tanks were measured. The high value of Kd, above 5.0 litres per gram of suspended solids, showed most of the musks could be removed by sludge through the adsorption process; thus the removal rate from the water phase caused by adsorption in the wastewater treatment plant can be predicted.

Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography.

BACKGROUND: To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α-thalassemia HbH on the results of HbA1c assessment using ion-exchange high-performance liquid chromatography (IE-HPLC). METHODS: We enrolled five patients in which the results of the IE-HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy-mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA-HPLC) and turbidimetric inhibition immunoassay (TINIA). RESULTS: Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were ß41-42 /ßJ Bangkok and ßN /ßJ Bangkok , and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (ßN /ßE Hb genotype, 23.6% HbE content), HbG Taipei (ßN /ßG Taipei Hb genotype, 39.4% HbG Taipei content), and α-thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with ß-thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE-HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE-HPLC but not with the TINIA assay. There was no interference with BA-HPLC HbA1c results. CONCLUSIONS: HbJ Bangkok, HbE, HbG Taipei Hb, and α-thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE-HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels.

Opposing roles of ICAT and Wnt/ß-catenin signaling in NSC67657-induced monocytic differentiation.

NSC67657 is a new steroid drug that induces monocytic differentiation of acute myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects on expression of downstream targets of inhibitor of ß-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to ß-catenin, and this interaction is further increased in NSC67657-differentiated cells. ICAT overexpression decreases expression of Wnt downstream targets and increases sensitivity of HL60 cells to NSC67657, while ICAT silencing increases Wnt signaling and delays the NSC67657-induced cell differentiation. In addition, pharmacological inhibition of Wnt/ß-catenin signaling increases the NSC67657-induced cell differentiation, while activation of Wnt/ß-catenin signaling inhibits the differentiation, indicating Wnt/ß-catenin signaling inhibits NSC67657-induced monocytic differentiation of HL60 cells. Our data demonstrate the opposing roles of ICAT and Wnt signaling in the NSC67657-induced monocytic differentiation, and suggest that ICAT and Wnt signaling may serve as therapeutic targets for leukemia chemotherapy.

Evaluation of the Interference of Hemoglobin Variant J-Bangkok on Glycated Hemoglobin (HbA1c) Measurement by Five Different Methods.

Objective The interference of the hemoglobin variant (Hb J-Bangkok) was evaluated on 4 different glycated hemoglobin assays and compared with a reference immuno assay. Methods An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of Hb J-Bangkok caused a statistically significant difference in HbA1c results compared with a reference immuno assay. Statistical analysis was performed on the difference of the estimated average glucose calculated from HbA1c values and fasting plasma glucose in the Hb J-Bangkok variant group using the different detection systems. Deming regression analysis was used to determinate whether Hb J-Bangkok had a significant interference on HbA1c results using an HbA1c±10% relative bias at 6% and 9% HbA1c as evaluation limits. Results Turbidimetric inhibition immunoassay method, and enzymatic methods were not affected by Hb J-Bangkok. However, Hb J-Bangkok showed statistically significant interference to the two ion-exchange high-performance liquid chromatography methods. Conclusion When performing HbA1c tests, clinical laboratory personnel should identify the Hb variant and select the appropriate methods or use alternative indicators.

Colorimetric detection of genetically modified organisms based on exonuclease III-assisted target recycling and hemin/G-quadruplex DNAzyme amplification.

An isothermal colorimetric method is described for amplified detection of the CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on (a) target DNA-triggered unlabeled molecular beacon (UMB) termini binding, and (b) exonuclease III (Exo III)-assisted target recycling, and (c) hemin/G-quadruplex (DNAzyme) based signal amplification. The specific binding of target to the G-quadruplex sequence-locked UMB triggers the digestion of Exo III. This, in turn, releases an active G-quadruplex segment and target DNA for successive hybridization and cleavage. The Exo III impellent recycling of targets produces numerous G-quadruplex sequences. These further associate with hemin to form DNAzymes and hence will catalyze H2O2-mediated oxidation of the chromogenic enzyme substrate ABTS2- causing the formation of a green colored product. This finding enables a sensitive colorimetric determination of GMO DNA (at an analytical wavelength of 420 nm) at concentrations as low as 0.23 nM. By taking advantage of isothermal incubation, this method does not require sophisticated equipment or complicated syntheses. Analyses can be performed within 90 min. The method also discriminates single base mismatches. In our perception, it has a wide scope in that it may be applied to the detection of many other GMOs. Graphical abstract An isothermal and sensitive colorimetric method is described for amplified detection of CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on target DNA-triggered molecular beacon (UMB) termini-binding and exonuclease III assisted target recycling, and on hemin/G-quadruplex (DNAzyme) signal amplification.

[Spectroscopic Studies on the Host Plant Selection Mechanism of Trabala vishnou gigantina Yang (Lepidoptera: Lasiocampidae)].

Trabala vishnou gigantina Yang (Lepidoptera: Lasiocampidae) is a polyphagous forestry pest whose periodic breaking out results in great economic damage including total crop failure to forestry and fruit production in China. In this study, in order to improve the understanding of the host plant selection mechanism of T. vishnou gigantina larvae, locust, caragana, willow, poplar, apricot and sea-buckthorn were used as potential host plants for the test. Two-way choice experiment method was used to study the T. vishnou gigantina Yang feeding preferences of the six kinds of plants. Moreover, the chemical component and physical structure of six plants were analyzed with Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Among the six plants, T. vishnou gigantina larvae showed a strong preference for sea-buckthorn, followed by, apricot, willow, poplar, locust, and caragana. The FTIR analysis displayed that those six plants presented similar characteristic on absorption peak position, peak amount, and shape. The targets (1 154/1 733, 1 154/898) by FTIR showed that lipids and polysaccharide were major nutriments to affect the host plant selection of T. vishnou gigantina larvae. The XRD results showed that crystallinity index (CrI) also could affect the host plant selection of T. vishnou gigantina larvae. In this research, spectroscopy technology was firstly applied to the study of interactive relationship between insect and host, which would blaze a trail for intensive study of host plant selection mechanism of insect at molecular level.