Inhibition of Cardiac Kv4.3/KChIP2 Channels by Sulfonylurea Drug Gliquidone.

The Kv4.3 channel features fast N-type inactivation and also undergoes a slow C-type inactivation. The gain-of-function mutations of Kv4.3 channels cause an inherited disease called Brugada syndrome (BrS), characterized by a shortened duration of cardiac action potential repolarization and ventricular arrhythmia. The sulfonylurea drug gliquidone, an ATP-dependent K+ channel antagonist, is widely used for the treatment of type 2 diabetes. Here, we report a novel role of gliquidone in inhibiting Kv4.3 and Kv4.3/KChIP2 channels that encode the cardiac transient outward K+ currents responsible for the initial phase of action potential repolarization. Gliquidone results in concentration-dependent inhibition of both Kv4.3 and Kv4.3/KChIP2 fast or steady-state inactivation currents with an IC50 of approximately 8 µM. Gliquidone also accelerates Kv4.3 channel inactivation and shifts the steady-state activation to a more depolarizing direction. Site-directed mutagenesis and molecular docking reveal that the residues S301 in the S4 and Y312A and L321A in the S4-S5 linker are critical for gliquidone-mediated inhibition of Kv4.3 currents, as mutating those residues to alanine significantly reduces the potency for gliquidone-mediated inhibition. Furthermore, gliquidone also inhibits a gain-of-function Kv4.3 V392I mutant identified in BrS patients in voltage- and concentration-dependent manner. Taken together, our findings demonstrate that gliquidone inhibits Kv4.3 channels by acting on the residues in the S4 and the S4-S5 linker. Therefore, gliquidone may hold repurposing potential for the therapy of Brugada syndrome. SIGNIFICANCE STATEMENT: We describe a novel role of gliquidone in inhibiting cardiac Kv4.3 currents and the channel gain-of-function mutation identified from patients with Brugada syndrome, suggesting its repurposing potential for therapy for the heart disease.

Plastid phylogenomics of the tribe potentilleae (Rosaceae).

The tribe Potentilleae comprises approximately 1700 species in 13 genera, making it one of the largest of the 16 tribes in Rosaceae. Our understanding of the composition and relationships among members of Potentilleae has advanced dramatically with the application of molecular markers in the last two decades. Yet there is still much work remaining toward a robust phylogenetic framework for the entire Potentilleae and a comprehensive genus-level dating framework for the tribe. The goals of the present study were to establish a phylogenetic framework for Potentilleae, infer the origin and diversification of the tribe using a temporal framework, and explore the taxonomic implications in light of the updated phylogenetic framework. We used the plastome sequences from 158 accessions representing 139 taxa covering all 13 recognized genera of the tribe to reconstruct the Potentilleae phylogeny. High phylogenetic resolution was recovered along the Potentilleae backbone. Two major clades were recovered within Potentilleae, corresponding to the two subtribes Fragariinae and Potentillinae. Within Fragariinae, two subclades were recovered. In one subclade, Sibbaldia sensu stricto is sister to a clade containing Sibbaldianthe, Comarum, Farinopsis, and Alchemilla sensu lato. In the other subclade, Fragaria is sister to a clade comprising Chamaerhodos, Chamaecallis, Drymocallis, Dasiphora, and Potaninia. Within Potentillinae, Argentina is sister to Potentilla sensu stricto. Within Potentilla sensu stricto, clade Himalaya is sister to Alba, and the Himalaya-Alba clade together is sister to a clade comprising Reptans, Potentilla ancistrifolia Bunge, Fragarioides, Ivesioid, and Argentea. Divergence time estimates indicated that tribe Potentilleae originated during the middle Eocene, and subtribes Fragariinae and Potentillinae diverged around the Eocene-Oligocene transition, and divergence times dated for Potentilleae genera ranged from the early Miocene to the late Pleistocene.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

Variety and quantity of dietary protein intake from different sources and risk of new-onset diabetes: a Nationwide Cohort Study in China.

BACKGROUND: The relation of the variety and quantity of different sources of dietary proteins intake and diabetes remains uncertain. We aimed to investigate the associations between the variety and quantity of proteins intake from eight major food sources and new-onset diabetes, using data from the China Health and Nutrition Survey (CHNS). METHODS: 16,260 participants without diabetes at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for both types and quantity of proteins. New-onset diabetes was defined as self-reported physician-diagnosed diabetes or fasting glucose ≥7.0mmol/L or glycated hemoglobin ≥6.5% during the follow-up. RESULTS: During a median follow-up of 9.0 years, 1100 (6.8%) subjects developed diabetes. Overall, there were U-shaped associations of percentages energy from total protein, whole grain-derived and poultry-derived proteins with new-onset diabetes; J-shaped associations of unprocessed or processed red meat-derived proteins with new-onset diabetes; a reverse J-shaped association of the fish-derived protein with new-onset diabetes; L-shaped associations of egg-derived and legume-derived proteins with new-onset diabetes; and a reverse L-shaped association of the refined grain-derived protein with new-onset diabetes (all P values for nonlinearity<0.001). Moreover, a significantly lower risk of new-onset diabetes was found in those with a higher variety score of protein sources (per score increment; HR, 0.69; 95%CI, 0.65-0.72). CONCLUSIONS: There was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset diabetes.

Relationship of several serum folate forms with kidney function and albuminuria: cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2011-2018.

We aim to examine the relation of several folate forms (5-methyltetrahydrofolate (5-mTHF), unmetabolised folic acid (UMFA) and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18 757 participants from National Health and Nutrition Examination Survey 2011-2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 ml/min/1·73 m2), microalbuminuria (albumin:creatinine ratio (ACR) of 30-299 mg/g) and macroalbuminuria (ACR ≥ 300 mg/g). Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0·71; 95 % CI: 0·57, 0·87) and macroalbuminuria (OR, 0·65; 95 % CI: 0·46, 0·91) in participants in quartiles 3-4 (v. quartiles 1-2; both Pfor trend across quartiles <0·05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartiles 2-4 (v. quartile 1; OR, 2·12; 95 % CI: 1·45, 3·12; Pfor trend <0·001) and higher prevalence of macroalbuminuria in participants in quartile 4 (v. quartiles 1-3; OR, 1·46; 95 % CI: 1·06, 2·01; Pfor trend <0·001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all Pfor trend <0·01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, was associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.

Associations of prenatal exposure to perfluoroalkyl substances with preterm birth: A family-based birth cohort study.

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure.

Pregnancy outcomes of fetuses with congenital heart disease after a prenatal diagnosis with chromosome microarray.

OBJECTIVE: To evaluate the pregnancy outcomes of fetuses with congenital heart disease (CHD) after chromosome microarray (CMA)-based prenatal diagnosis. METHOD: Amniocentesis was performed in 1035 pregnant women carrying fetuses with CHD between September 2014 and December 2019. Chromosomal aberrations in fetuses with CHD were evaluated using CMA. The pregnancy outcomes were followed up from 6 months to 5 years. RESULTS: The overall CHD detection rate by CMA was 10.1% (105/1035; 50 fetuses: aneuploidy, 55 fetuses: pathogenic or likely pathogenic copy number variations). Among 1003 fetuses who were followed up, 4, 236, 763, and 18 cases were of miscarriages, pregnancy termination, live births, and postnatal deaths, respectively. Self-healed CHD was observed in 401 (52.6%) fetuses. The pregnancy termination rate of fetuses with chromosomal anomalies was significantly higher than that of fetuses without chromosomal anomalies (93.1% vs. 15.5%, p < 0.001). However, other pregnancy outcomes, including mortality, preterm labor, and low-weight birth rate, were similar between the two groups. CONCLUSION: The outcome of CMA is an important factor influencing parents' choice of whether to continue the pregnancy. Self-healing rate of prenatal diagnosed CHD is high. The mortality and morbidity of fetuses with CHD following prenatal CMA testing are relatively low.

Accelerated toluene degradation over forests around megacities in southern China.

Toluene is a typical anthropogenic pollutant that has profound impacts on air quality, climate change, and human health, but its sources and sinks over forests surrounding megacities remain unclear. The Nanling Mountains (NM) is a large subtropical forest and is adjacent to the Pearl River Delta (PRD) region, a well-known hotspot for toluene emissions in southern China. However, unexpectedly low toluene concentrations (0.16 ± 0.20 ppbv) were observed at a mountaintop site in NM during a typical photochemical period. A backward trajectory analysis categorized air masses received at the site into three groups, namely, air masses from the PRD, those from central China, and from clean areas. The results revealed more abundant toluene and its key oxidation products, for example, benzaldehyde in air masses mixed with urban plumes from the PRD. Furthermore, a more than three times faster degradation rate of toluene was found in this category of air masses, indicating more photochemical consumption in NM under PRD outflow disturbance. Compared to the categorized clean and central China plumes, the simulated OH peak level in the PRD plumes (15.8 ± 2.2 × 106 molecule cm-3) increased by approximately 30% and 55%, respectively, and was significantly higher than the reported values at other background sites worldwide. The degradation of toluene in the PRD plumes was most likely accelerated by increased atmospheric oxidative capacity, which was supported by isoprene ozonolysis reactions. Our results indicate that receptor forests around megacities are not only highly polluted by urban plumes, but also play key roles in environmental safety by accelerating the degradation rate of anthropogenic pollutants.

Association of visceral adiposity index with new-onset type 2 diabetes and impaired fasting glucose in hypertensive Chinese adults.

PURPOSE: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults. METHODS: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit. RESULTS: Over a median of 4.5 years' follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08-1.56) and new-onset IFG (OR 1.28; 95% CI 1.08-1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05). CONCLUSION: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components. LEVEL OF EVIDENCE: Level III, a well-designed cohort.

Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer.

Drug resistance is always a great obstacle in any endocrine therapy of breast cancer. Although the combination of endocrine therapy and targeted therapy has been shown to significantly improve prognosis, refractory endocrine resistance is still common. Dysregulation of the Hippo pathway is often related to the occurrence and the development of many tumors. Targeted therapies of this pathway have played important roles in the study of triple negative breast cancer (TNBC). Targeting the Hippo pathway in combination with chemotherapy or other targeted therapies has been shown to significantly improve specific antitumor effects and reduce cancer antidrug resistance. Further exploration has shown that the Hippo pathway is closely related to endocrine resistance, and it plays a "co-correlation point" role in numerous pathways involving endocrine resistance, including related pathways in breast cancer stem cells (BCSCs). Agents and miRNAs targeting the components of the Hippo pathway are expected to significantly enhance the sensitivity of breast cancer cells to endocrine therapy. This review initially explains the possible mechanism of the Hippo pathway in combating endocrine resistance, and it concludes by recommending endocrine therapy in combination with therapies targeting the Hippo pathway in the study of endocrine-resistant breast cancers.

Risk factors for mortality of critically ill patients with COVID-19 receiving invasive ventilation.

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation. Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation. Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients. Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.

Prenatal diagnosis of genetic aberrations in fetuses with short femur detected by ultrasound: A prospective cohort study.

OBJECTIVES: To investigate the genetic aberrations in fetuses with short femur and explore the relationships with respect to degree of femoral shortening and the initial diagnostic gestational age GA. METHODS: Singleton pregnancies with fetal short femur who consented to amniocentesis and to single nucleotide polymorphism (SNP) array and Sanger sequencing for G380R mutations in FGFR3 gene were enrolled in this 5-year period prospective study. Clinical follow-up assessments were performed after birth. RESULTS: Of a total of 161 fetuses, the prevalence of genetic aberrations was 16.2% (26/161), comprised of 65.4% (17/26) with chromosomal abnormalities and 34.6% (9/26) with G380R mutations. All fetuses with chromosomal abnormalities had FL 2-4SDs below GA. Fewer chromosomal abnormalities were detected in fetuses with short femurs presenting in the third trimester. Significantly more FGFR3 mutations were detected in fetuses with FL below -4SDs. All fetuses with FL 2-4SDs below GA diagnosed as achondroplasia were between 22 and 24 gestational weeks, and all of those diagnosed in third trimester had FL below -4SDs. CONCLUSION: In this small cohort study, we demonstrated that different degrees of femur shortness may be attributed to different genetic aberrations. SNP array should be regarded as the first-tier test for fetuses with FL 2-4SDs below GA. The prognoses for fetuses with FL 2-4SDs below GA was significantly better than those with FL below 4SDs.

Metabolic profiling of nanosilver toxicity in the gills of common carp.

Studies have shown silver nanoparticles (AgNPs) exposure can result in a series of toxic effects in fish gills. However, it is still unclear how AgNPs affect metabolite expression and their related molecular metabolic pathways in fish gills. In this study, we employed untargeted metabolomics to study the effects of AgNPs and silver supernatant ions on fish gill metabolites. The results showed that AgNPs can induce significant changes in 96 differentially expressed metabolites, which mainly affect amino acid metabolism and energy metabolism in fish gills. Among these metabolites, AgNPs specifically induce significant changes in 72 differentially expressed metabolites, including L-histidine, L-isoleucine, L-phenylalanine, and citric acid. These metabolites were significantly enriched in the pathways of aminoacyl-tRNA biosynthesis, ABC transporters, and the citrate cycle. In contrast, Ag+ supernatant exposure can specifically induce significant changes in 14 differentially expressed metabolites that mainly interfere with sphingolipid metabolism in fish gills. These specifically regulated fish gill metabolites include sphinganine, sphingosine, and phytosphingosine, which were significantly enriched in the sphingolipid metabolism pathway. Our results clearly reveal the effects and potential toxicity mechanisms of AgNPs on fish gill metabolites. Furthermore, our study further determined the unique functions of released silver ions in AgNPs toxicity in fish gills.

[Application of Array-based Comparative Genomic Hybridization in the Prenatal Diagnosis of Fetal Chromosomal Aberration in Gravidas with Advanced Age].

OBJECTIVE: To evaluate the clinical application of array-based comparative genomic hybridization (a-CGH) in the prenatal diagnosis of fetal chromosomal aberrations in gravidas with advanced maternal age (AMA). METHODS: A total of 3 677 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to AMA were selected. Array-CGH was performed on the Agilent CGX TM (8X60K) platform and the data were analyzed by the Genoglyphix software. RESULTS: The overall detection rate of chromosomal aberration was 2.04% (75/3677), with 53.33% (40/75) being aneuploidies, including 22 cases of trisomy-21, 5 cases of trisomy-18, 8 cases with XXY, 3 cases of XYY and 2 cases of mosaic monosomy X, 32.00% (24/75) being pathogenic copy number variations (pCNVs), including 19 cases of microdeletion and 5 cases of microduplication, with the fragment size ranging from 323 kb to 26 780 kb, and 14.67% (11/75) being likely pathogenic CNVs (lpCNVs), including 7 cases of microdeletion and 7 cases of microduplication, with the fragment size ranging from 358 kb to 16 873 kb. Besides, the detection rate of CNVs of unknown clinical significance (VUS) was 0.84% (31/3 677). The detection rate of aneuploidies increased significantly with increased maternal age ( P<0.05). However, there were no significant differences in the detection rate of p/lpCNVs among different maternal age groups ( P>0.05). CONCLUSION: Our findings suggest that, compared with traditional karyotype analysis, a-CGH not only detects aneuploidies, but also detect pathogenic CNVs, including microdeletion/microduplication syndromes. The detection rate of fetal aneuploidies was closely correlated to maternal age. However, no correlation was found between the detection rate of p/lpCNVs and maternal age.

[Application of Array-based Comparative Genomic Hybridization in Diagnostic Assessment of Abnormal Prenatal Serological Screening Results of Down's Syndrome].

OBJECTIVE: To explore the application of array-based comparative genomic hybridization (a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down's syndrome (DS). METHODS: A total of 3 578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected. The samples were categorized into 3 groups, 2 624 in the high-risk group, 662 in the borderline-risk group, and 292 in the abnormal multiple of median (MoM) group. a-CGH was performed on the Agilent CGX ™ (8×60K) platform and the data were analyzed by the Genoglyphix ® software. RESULTS: The overall detection rate of chromosomal abnormalities was 3.38% (121/3 578). Among the chromosomal abnormalities, 49.59% (60/121) was aneuploidies, 42.15% (51/121) was pathogenic copy number variants (pCNVs), and 8.26% (10/121) was likely pathogenic CNVs (lpCNVs). The detection rate of copy number variant of uncertain significance (VUS) was 1.03% (37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54% (93/2 624), 2.87% (19/662) and 3.08% (9/292), respectively; the detection rate of p/lp CNVs was 1.64% (43/2 624), 1.81% (12/662) and 2.05% (6/292), respectively; the detection rate of trisomy 21 and trisomy 18 was 1.37% (36/2 624), 0.76% (5/662) and 0.34% (1/292) in the three groups, respectively. There were no significant differences in all the detection rate among these groups ( P>0.05). One sample with X(51)/XYY(49) confirmed by fluorescence in situ hybridization (FISH) was misdiagnosed by a-CGH. CONCLUSION: Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS. It can also be used to detect CNVs of microdeletion/microduplication syndromes.

Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis in fetuses with ultrasound anomalies in the urinary system.

OBJECTIVES: This study aimed to explore the relationships between urinary anomalies and copy number variations (CNVs) in fetuses and provide information for prenatal diagnosis and genetic counseling for parents. METHODS: Three hundred seventeen fetuses with urinary system anomalies detected by prenatal ultrasound were enrolled; 251 had isolated urinary system anomalies, and 66 had nonisolated system anomalies. CMA was performed on the Affymetrix 750K platform. RESULTS: The frequency of chromosomal aberrations in fetuses with urinary system anomalies was 11.04%, including 6.31% with pathogenic CNVs (pCNVs). The detection rate of chromosomal abnormalities was significantly higher for the fetuses with nonisolated urinary system anomalies than for those with isolated urinary system anomalies. Seven fetuses (25.93%) with echogenic kidneys were identified with pCNVs; this detection rate was significantly higher than that for fetuses with other urinary anomalies. A 17q12 deletion was detected in eight fetuses with urinary anomalies, accounting for 40% of pCNVs. CONCLUSION: CMA is especially valuable in the prenatal diagnosis of fetuses with urinary system anomalies. The pCNV rates differed between the isolated and nonisolated subgroups of urinary anomalies. Fetuses with echogenic kidneys had the highest rate of pCNVs. The 17q12 deletion was the most frequent pCNV in fetuses with urinary anomalies.

[Research progress on characteristics and applications of melanin nanoparticles].

Melanin nanoparticles (MNPs) not only retain the inherent characteristics of melanin (metal ion chelation, photothermal conversion property, etc.), but also can exhibit more excellent properties, such as high dispersion stability, good biocompatibility and biodegradability, etc. Furthermore, these performances can be enhanced to target the specific sites and treat diseases by the surface modification or combination with functional substance. In this paper, the characteristics, preparation methods and applications of MNPs were reviewed. It provides a reference for further development of application for MNPs, and theoretical basis for practice in biology, medicine and so on.

Nile Red Loaded PLGA Nanoparticles Surface Modified with Gd-DTPA for Potential Dual-Modal Imaging.

Here, a novel poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for magnetic resonance (MR) and fluorescence imaging was developed for cell imaging. PLGA NPs loaded with fluorescent dye Nile red (NR) and surface-coated with poly(ethyleneimine) (PEI) were produced in a single step nanoprecipitation process. Diethylenetriamine pentaacetic dianhydride (DTPA) was conjugated to PLGA/NR@PEI NPs through amidation reaction between -COOH of DTPA and -NH2 of PEI, which can chelate gadolinium (Gd3+) as an MR imaging contrast agent. The PLGA/NR@PEI-DTPA-Gd NPs exhibited a uniform particle size of -200 nm and were stable in culture medium. These NPs had a high T relaxivity (R1) of 28.36 mM(-1)S(-1). They did not introduce serious cytotoxicity against A549 lung cancer cells. Furthermore, fluorescence and MR imaging studies on A549 lung cancer cells in vitro revealed that PLGA/NR@PEI-DTPA-Gd NPs can serve as an efficient fluorescence/MR dual-modality imaging nanoprobe.

Integrative Indicator for Assessing the Alert Levels of Algal Bloom in Lakes: Lake Taihu as a Case Study.

Algal blooms have recently become one of the most serious environmental problems in eutrophic freshwater ecosystems worldwide. Although many observation and simulation approaches have been applied to predict algal blooms, few studies have addressed the alert levels of algal blooms using integrative indicators in a large lake with multiple service function and significant horizontal heterogeneity. This study developed an integrative indicator assessment system (IIAS) to rank the alert level of algal blooms. In the IIAS, algal biomass, area percentage, distance from drinking water intake points, distance from scenic zones and duration of algal bloom were used as indicators to calculate a comprehensive alert level, which was classified into five grades (Vigilance, Low, Moderate, High, and Severe). Lake Taihu was taken as a case study to assess the comprehensive alert level of algal blooms in 2007 and 2010. The comprehensive alert level showed obvious spatial-temporal patterns, with an acceptable accuracy in Lake Taihu. The comprehensive alert levels were relatively higher in typical phytoplankton subzones than typical hydrophytes subzones and are more sensitive to weight factor in the northern and western subzones where high biomass usually occurs. Case study showed a very good application of the proposed comprehensive alert level assessment methodology, which can be adjusted to predict the degree of hazard of algal blooms in multi-service function large lakes to help the government and decision makers to act to prevent the disaster from algal bloom spreading.

Comparative chloroplast genomes of Argentina species: genome evolution and phylogenomic implications.

The genus Argentina Hill belongs to the tribe Potentilleae Sweet and contains approximately 75 species predominantly distributed in the Sino-Himalayan region and the Malesian archipelago. So far we have less knowledge on the phylogenetic relationships within Argentina owing to limited sampling of Argentina taxa or gene fragments in previous studies. Moreover, to date there is no phylogenetic study on Argentina from the perspective of comparative chloroplast (cp) genomics. Here we performed comparative genomic analyses on the cp genomes of 39 accessions representing 18 taxa of Argentina. The Argentina cp genomes presented the typical quadripartite structure, with the sizes ranging from 155 096 bp to 157 166 bp. The 39 Argentina cp genomes contained a set of 112 unique genes, comprising four ribosomal RNA (rRNA) genes, 30 transfer RNA (tRNA) genes, as well as 78 protein-coding genes (PCGs). The cp genome organization, gene content and order in Argentina were highly conserved, but some visible divergences were present in IR/SC boundary regions. Ten regions (trnH-GUG-psbA, trnG-GCC-trnfM-CAU, trnD-GUC-trnY-GUA, rpl32-trnL-UAG, atpH-atpI, rps16-trnQ-UUG, trnS-GCU-trnG-UCC, ndhF-rpl32, trnR-UCU-atpA, and accD-psaI) were identified as excellent candidate DNA markers for future studies on species identification, population genetics and phylogeny of Argentina. Our results indicated that Argentina is monophyletic. In the current sampling, the A. smithiana - A. anserina clade was sister to the remainder of Argentina. Our results corroborated the previous taxonomic treatments to transfer A. phanerophlebia and A. micropetala from the genus Sibbaldia L. to Argentina. Our results showed close relationships among A. stenophylla, A. microphylla, A. taliensis, and A. tatsienluensis, congruent with previous studies based on the morphology of these species. Twenty-six genes (rps3, rps15, rps16, rps19, rpl16, rpl20, rpl22, rpoA, rpoB, rpoC1, rpoC2, atpA, atpF, psbB, psbF, ndhA, ndhB, ndhC, ndhD, ndhF, rbcL, accD, ccsA, matK, ycf1, ycf2) were with sites under positive selection, and adaptive evolution of these genes might have played crucial roles in Argentina species adaptation to the harsh mountain environment. This study will facilitate future work on taxonomy, phylogenetics, and adaptive evolution of Argentina.