Application of a newly constructed NGS panel with 45 X-linked microhaplotypes demonstrates the unique value of X-MH for kinship testing and mixture analysis.

X-linked microhaplotypes (X-MHs) have the potential to be a valuable supplementary tool in complex kinship identification or the resolution of DNA mixtures, because they bring together the distinctive genetic pattern of X chromosomal markers and the benefits of microhaplotypes (MHs). In this study, we used the 1000 Genome database to screen and select 63 X-MHs; 18 MHs were filtered out though a batch sequencing assessment of the DNA samples collected from 112 unrelated Chinese Han individuals. The resulting 45-plex panel performed well in comprehensive assessments including repeatability, sensitivity, species specificity, resistance to PCR inhibitors or degradation, mutation rate, and accuracy in detecting DNA mixture samples. The minimum amount of DNA template that can be tested with this panel is 0.5 ng. Additionally, the alleles of the minor contributor can be accurately detected when the mixture rate is larger than 1:9 in female-male mixture or 1:19 in male-male mixture. Then, we calculated population parameters on each MH based on the allele frequency data obtained from the sequence results of the aforementioned 112 unrelated samples. Combining these parameters on each MH, it can be calculated that TDPm, TDPf, CPET, CPEDFM, CPEDFF and CNCEP3 of the 45-plex system were 1-8.99×10-13, 1-1.62×10-19, 0.9999999995, 0.9999981, 0.9955, 0.9999971 and 0.99940, respectively, indicating that the panel is capable in personal identification and parentage testing. To reveal the unique advantage of X-MHs in the analyses of complex kinship and male DNA mixture, further assessments were made. For complex kinship identification, 22 types of individual pairs with different second-degree kinship were simulated and different types of likelihood ratios (LR) were calculated for each. The results revealed that the panel can achieve accuracy of approximately 70 %∼80 % when dividing each of the three types of second-degree kinships into three or four groups. Theoretically, such sub-division cannot be done by using independent autosomal markers. For male DNA mixture analysis without suspects, the maximum likelihood ratio strategy was derived and employed in the estimation of the number of male contributors (NOMC). Simulations were conducted to verify the efficacy of the 45-plex panel in the field and to compare it with autosomal markers by assuming the 45 MHs as autosomal ones. The results showed that X-MHs can achieve higher accuracy in the estimation of NOMC than autosomal ones when the mixed males were unrelated. The results highlighted the unique value of X-linked MHs in complex kinship and male mixture analyses.

The handgrip strength and risk of depressive symptoms: a meta-analysis of prospective cohort studies.

PURPOSE: Many studies have investigated the association between handgrip strength (HGS) and depressive symptoms, but the conclusion remain controversial. We performed a meta-analysis to evaluate the longitudinal association between HGS and risk of depressive symptoms. METHODS: PubMed, PSYCINFO and EMBASE databases were searched for eligible publications up to April 2020. Pooled relative risks (RRs) with 95% confidence intervals were calculated using random-effects model. Publication bias was estimated using Egger's test and the funnel plot. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. RESULTS: The present meta-analysis included 8 cohort studies with 30,727 participants. Overall, higher HGS was related to a decreased risk of depressive symptoms: the pooled risk ratio (RR) of 0.74 [95% confidence intervals (CI) 0.65-0.85] with a moderate heterogeneity (I2 = 60.5%, P = 0.013). HGS was significantly associated with a reduced risk of depressive symptoms in males (RR = 0.69; 95% CI 0.50-0.94), but not in females. CONCLUSIONS: Lower HGS was associated with an increased risk of depressive symptoms. Further studies are needed to confirm these findings and to investigate the sex differences.

lncRNA H19 acts as a ceRNA to regulate the expression of CTGF by targeting miR-19b in polycystic ovary syndrome.

The etiology of polycystic ovary syndrome (PCOS) is complex and the pathogenesis is not fully understood. Some studies have shown that dysregulation of ovarian granulosa cells may be related to abnormal follicles and excessive androgen in women with PCOS. Our team has also confirmed the high expression status of H19 in PCOS patients in the early stage. However, the relationship between H19 and miR-19b in the development of PCOS is still unknown. Therefore, we used bioinformatics to predict the binding sites of human H19 and miR-19b, and of miR-19b and CTGF genes. After the silencing and overexpression of H19, real-time polymerase chain reaction (PCR) was used to detect the expressions of H19, miR-19b, and CTGF. Western blotting was used to detect CTGF protein. Proliferation of KGN cells after H19 silencing was detected by CCK8. Flow cytometry was used to detect the apoptosis of KGN cells after H19 silencing. After the overexpression of H19, it was found that the expression of miR-19b gene decreased and the expression of CTGF increased, whereas silencing of H19 did the opposite. In addition, H19 could promote cell proliferation and decrease cell apoptosis. Finally, luciferase reporter assays showed that the 3'-end sequences of lncRNA H19 and CTGF contained the binding site of miR-19b. In conclusion, our study indicated that lncRNA H19 acted as a ceRNA to bind to miR-19b via a "sponge" to regulate the effect of CTGF on KGN cells, which may play a vital role in PCOS.

A cross-sectional study of blood selenium concentration and cognitive function in elderly Americans: National Health and Nutrition Examination Survey 2011-2014.

BACKGROUND: Cognitive decline can develop into mild cognitive impairment, a high-risk factor in the progression of Alzheimer's disease. The antioxidant micronutrient selenium may have some effect on preventing cognitive decline, but the association between whole blood selenium concentration and cognitive function remains controversial. AIM: To investigate the association between whole blood selenium concentration and cognitive function score in elderly Americans. SUBJECTS AND METHODS: Data was obtained from the national health and nutrition survey between 2011 and 2014. A general linear model was used to adjust for possible risk factors to analyse the association between blood selenium concentration and cognitive function. RESULTS: 2068 participants were included in our study, and the average blood selenium concentration was high at 195.08 µg/L. The risk of lower cognitive scores was higher in people with lower blood selenium concentration (p < 0.05). The lower cognition may also be associated with one or more of the following characteristics: older, male, had a low poverty-income ratio, low education level, and consumed less alcohol. Related conditions such as stroke, diabetes and high blood pressure may also affect cognitive scores. CONCLUSIONS: Higher blood selenium is associated with higher cognitive scores in elderly Americans.

Association between triclocarban and triclosan exposures and the risks of type 2 diabetes mellitus and impaired glucose tolerance in the National Health and Nutrition Examination Survey (NHANES 2013-2014).

BACKGROUND: There has been increasing interest in the concept that exposure to environmental chemicals may be contributing factors to epidemics of diabetes mellitus (DM). Triclocarban and triclosan (TCs) are synthetic antibacterial chemicals that are widely used in personal care products. Studies have shown that TCs are endocrine disruptors that alter metabolic conditions. However, it remains unclear whether exposure to TCs is a risk factor for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). OBJECTIVE: We explored the hypothesis that TCs exposure is associated with an increased risk of IGT and T2DM. METHOD: To test our hypothesis, we analyzed the U.S. National Health and Nutrition Examination Survey (NHANES) cross-sectional data from 2013 to 2014. IGT and T2DM were diagnosed based on an oral glucose tolerance test (OGTT) and the WHO standards. The levels of urinary TCs were measured using an HPLC-MS/MS method that NHANES investigators developed. The association between urinary TCs status and IGT and T2DM was examined separately in men and women using multivariable logistic regression models adjusted for age, race, BMI, education, ratio of family income to poverty, smoking, exercise and hypertension. RESULTS: Nine hundred US participants (429 men and 471 women) were included in the analysis, of whom 242 (26.89%) were diagnosed with T2DM and 117 (13.00%) had IGT. Among women, there was a significant positive association between triclocarban, but not triclosan exposure and T2DM (OR: 1.79, 95% CI: 1.05, 2.05) after adjusting for potential confounding factors. Among men, no significant association between TCs exposure and IGT or T2DM was observed. CONCLUSIONS: Triclocarban exposure may increase the risk of T2DM in the women, although additional studies are needed to confirm the results of this study and to investigate the underlying mechanisms.

lncRNA H19 acts as a ceRNA to regulate the expression of CTGF by targeting miR-19b in polycystic ovary syndrome

The etiology of polycystic ovary syndrome (PCOS) is complex and the pathogenesis is not fully understood. Some studies have shown that dysregulation of ovarian granulosa cells may be related to abnormal follicles and excessive androgen in women with PCOS. Our team has also confirmed the high expression status of H19 in PCOS patients in the early stage. However, the relationship between H19 and miR-19b in the development of PCOS is still unknown. Therefore, we used bioinformatics to predict the binding sites of human H19 and miR-19b, and of miR-19b and CTGF genes. After the silencing and overexpression of H19, real-time polymerase chain reaction (PCR) was used to detect the expressions of H19, miR-19b, and CTGF. Western blotting was used to detect CTGF protein. Proliferation of KGN cells after H19 silencing was detected by CCK8. Flow cytometry was used to detect the apoptosis of KGN cells after H19 silencing. After the overexpression of H19, it was found that the expression of miR-19b gene decreased and the expression of CTGF increased, whereas silencing of H19 did the opposite. In addition, H19 could promote cell proliferation and decrease cell apoptosis. Finally, luciferase reporter assays showed that the 3′-end sequences of lncRNA H19 and CTGF contained the binding site of miR-19b. In conclusion, our study indicated that lncRNA H19 acted as a ceRNA to bind to miR-19b via a "sponge" to regulate the effect of CTGF on KGN cells, which may play a vital role in PCOS.

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population.

Objective: To evaluate the potential association between the genetic variants in miRNA processing genes (RAN, XPO5, DICER1, and TARBP2) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes. Methods: We conducted a case-control study in genotyping of five polymorphic loci, including RAN rs14035, XPO5 rs11077, DICER1 rs13078, DICER1 rs3742330, and TARBP2 rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too. Results: We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in DICER1 rs13078 (OR: 0.64; 95%CI: 0.42-0.95; P: 0.026). The AA haplotype in DICER1 was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42-0.94; P-value: 0.023). T2DM patients with the TT+TC genotype at RAN rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04-3.45; P-value: 0.037). We also identified two three-factor interaction models. One is a three-factor [DICER1 rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25-28.26; P = 0.025). Another three-factor [RAN rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM (OR = 41.60, 95%CI = 11.75-147.35, P < 0.001). Conclusion: Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, DICER1 and RAN, and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population.

Toxoplasma gondii Cathepsin C1 inhibits NF-κB signalling through the positive regulation of the HIF-1α/EPO axis.

Toxoplasma gondii has evolved many successful strategies for immune evasion. However, the parasite-derived effectors involved in modulating NF-κB signalling pathway are largely unknown. T. gondii Cathepsin C1 (CPC1) is widely conserved among T. gondii strains and is important for T. gondii intracellular growth and proliferation. Our study showed that CPC1 protein could abrogate NF-κB activation after screening dense granule proteins. CPC1 suppressed NF-κB activation at or downstream of p65 and decreased the production of IL-1, IL-8, IL-6, IL-12, and TNF-α. Western blot analysis revealed that CPC1 inhibited phospho-p65 and CPC1 proteins primarily settled in cytoplasm. RNA sequencing analysis revealed that overexpression of CPC1 significantly upregulated erythropoietin (EPO), which can be induced by the hypoxia-inducible factor -1α (HIF-1α) during hypoxia. Furthermore, dual-luciferase reporter assays confirmed that CPC1 upregulated HIF-1α. Finally, both the knockdown of EPO and restriction of HIF-1α partially eliminated the suppression impact of CPC1 on the NF-κB signalling pathway. Our study identified a previously unrecognized role of CPC1 in the negative regulation of NF-κB activation through positive regulation of the HIF-1α/EPO axis. For the first time, CPC1 was shown to play an important role in immune evasion during T. gondii infection.

Li-O2 Cell with LiI(3-hydroxypropionitrile)2 as a Redox Mediator: Insight into the Working Mechanism of I- during Charge in Anhydrous Systems.

Redox mediators (RMs) have been widely applied to reduce the charge overpotential of nonaqueous lithium-oxygen (Li-O2) batteries. Among the reported RMs, LiI is under hot debate with lots of controversial reports. However, there is a limited understanding of the charge mechanism of I- in anhydrous Li-O2 batteries. Here, we study the chemical reactivity between the oxidized state of I- and Li2O2. We confirm that the Li2O2 particles could be chemically oxidized by I2 rather than I3- species. Furthermore, our work demonstrates that the generated I- from Li2O2 oxidation would combine with I2 to give I3- species, hindering further oxidation of Li2O2 by I2. To improve the working efficiency of I- RMs, we introduce a compound LiI(3-hydroxypropionitrile)2 (LiI(HPN)2) with a high binding ability of I-. Compared with LiI, the cell that contained LiI(HPN)2 shows a significantly increased amount of I2 species during charge and enhanced Li2O2 oxidation efficiency under the same working conditions.

Retrospective analysis of 55 twin neonates with haemolytic disease of the newborn.

Haemolytic disease is a condition characterized by anaemia and jaundice, and the course may be more complicated in twins. We investigated the demographic and laboratory characteristics of twins with haemolytic disease of the newborn (HDN) and compared these characteristics between groups categorized according to multiple birth status (twins vs. singletons) and conception method (assisted reproductive technology (ART) vs. spontaneous conception). Fifty-five twins with HDN and 253 singletons with HDN who were born during the same period (controls) were included in the study, and we performed comparisons between them. The results showed that twin infants were more likely to be premature, have a low birth weight and be conceived via ART than their singleton counterparts. Moreover, a variety of comorbidities were identified more frequently in twins with HDN than singletons with HDN. The minimum haemoglobin and the initial and maximum total bilirubin, albumin and complement 3 (C3) were all significantly lower in twins than in singletons; however, these two groups were not found to differ significantly by direct antiglobulin test (DAT) status. Twins conceived via ART had a lower minimum haemoglobin and initial bilirubin than twins conceived spontaneously. The results of this study suggested that neonatal comorbidities were more common in twins with HDN than singletons with HDN; however, DAT positivity did not appear to play a major role in the higher rates of comorbidities and lower concentration of haemoglobin observed in twins. Among twins with HDN, conception via ART may serve as a risk factor for increased disease severity.

Retrospective analysis of 30 severe autoimmune hemolytic anemia patients treated by whole blood exchange transfusion.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) results from the excessive destruction of red blood cells (RBCs). Nowadays, there is no exact treatment for severe AIHA and our current medical therapies do not effectively stop the progression of severe AIHA. Therapeutic plasma exchange (TPE) is used as emergency therapy that is sometimes helpful. Whole blood exchange (WBE) is based on TPE while its replacement liquids are donor RBCs and fresh plasma. We hypothesized that WBE transfusion might be able to control the process of acute hemolysis, avoid the hemolytic crisis, and improve severe hemolytic anemic symptoms rapidly. The objective was to investigate the efficiency of WBE on severe AIHA. STUDY DESIGN AND METHODS: Thirty severe AIHA patients were treated with WBE in our hospital from June 2003 to August 2013. An apheresis instrument (COBE Spectra, TerumoBCT) was employed in WBE procedure. We retrospectively analyzed the results of these severe anemic patients. RESULTS: Twelve hours after WBE treatment, 26 of 30 (86.7%) patients' Hb levels were elevated immediately. Their total bilirubin concentration, direct bilirubin levels, and titers of antibodies were decreased, and clinical symptoms were relieved rapidly. Two (6.7%) patients' hemolysis was stopped from deteriorating, one (3.3%) patient's hemolysis was not controlled by the treatment due to malignancy, and another (3.3%) patient died from pleural hemorrhage of Evans syndrome. CONCLUSION: This study suggests that WBE is an effective therapy for severe AIHA. Further investigation of this application is warranted.

[Clinical significance of anti-D IgG screening and titer detection in 286 RhD negative pregnant women].

OBJECTIVE: Anti-D IgG in RhD negative pregnant women is the main antibody of Rh-induced hemolytic disease of newborn (HDN). The study aimed to investigate the clinical significance of anti-D IgG screening and titer detection in RhD negative pregnant women. METHODS: Sera of 286 RhD negative pregnant women were collected. Microtube column indirect antiglobulin test was used to screen and identify anti-D IgG. The indirect antiglobulin test was used to test the titer of anti-D IgG. RESULTS: Anti-D IgG was identified in 21 cases (7.3%). The titer of anti-D showed an increasing trend with pregnancy progresses. The clinical outcomes of 12 fetuses (newborns) from positive anti-D pregnant women were observed. Two cases died in utero, 2 cases did not show abnormality and 8 cases had hemolysis. The 8 cases with hemolysis were treated with exchange transfusion or blood transfusion, and they had a good prognosis. CONCLUSIONS: The screening and titer detection of anti-D IgG in RhD negative pregnant women are valuable in the prediction and treatment of HDN.