Atomic-Scale Cryo-TEM Studies of the Electrochemistry of Redox Mediator in Li-O2 Batteries.

Rechargeable aprotic lithium (Li)-oxygen battery (LOB) is a potential next-generation energy storage technology because of its high theoretical specific energy. However, the role of redox mediator on the oxide electrochemistry remains unclear. This is partly due to the intrinsic complexity of the battery chemistry and the lack of in-depth studies of oxygen electrodes at the atomic level by reliable techniques. Herein, cryo-transmission electron microscopy (cryo-TEM) is used to study how the redox mediator LiI affects the oxygen electrochemistry in LOBs. It is revealed that with or without LiI in the electrolyte, the discharge products are plate-like LiOH or toroidal Li2 O2 , respectively. The I2 assists the decomposition of LiOH via the formation of LiIO3 in the charge process. In addition, a LiI protective layer is formed on the Li anode surface by the shuttle of I3 - , which inhibits the parasitic Li/electrolyte reaction and improves the cycle performance of the LOBs. The LOBs returned to 2e- oxygen reduction reaction (ORR) to produce Li2 O2 after the LiI in the electrolyte is consumed. This work provides new insight on the role of redox mediator on the complex electrochemistry in LOBs which may aid the design LOBs for practical applications.

Cinnamaldehyde prevents intergenerational effect of paternal depression in mice via regulating GR/miR-190b/BDNF pathway.

Paternal stress exposure-induced high corticosterone (CORT) levels may contribute to depression in offspring. Clinical studies disclose the association of depressive symptoms in fathers with their adolescent offspring. However, there is limited information regarding the intervention for intergenerational inheritance of depression. In this study we evaluated the intervention of cinnamaldehyde, a major constituent of Chinese herb cinnamon bark, for intergenerational inheritance of depression in CORT- and CMS-induced mouse models of depression. Depressive-like behaviors were induced in male mice by injection of CORT (20 mg·kg-1·d-1, sc) for 6 weeks or by chronic mild stress (CMS) for 6 weeks. We showed that co-administration of cinnamaldehyde (10, 20, or 40 mg·kg-1·d-1, ig) for 6 weeks in F0 males prevented the depressive-like phenotypes of F1 male offspring. In addition, co-administration of cinnamaldehyde (20 mg·kg-1·d-1, ig) for 4 weeks significantly ameliorated depressive-like behaviors of chronic variable stress (CVS)-stimulated F1 offspring born to CMS mice. Notably, cinnamaldehyde had no reproductive toxicity, while positive drug fluoxetine showed remarkable reproductive toxicity. We revealed that CMS and CORT significantly reduced testis glucocorticoid receptor (GR) expression, and increased testis and sperm miR-190b expression in F0 depressive-like models. Moreover, pre-miR-190b expression was upregulated in testis of F0 males. The amount of GR on miR-190b promoter regions was decreased in testis of CORT-stimulated F0 males. Cinnamaldehyde administration reversed CORT-induced GR reduction in testis, miR-190b upregulation in testis and sperm, pre-miR-190b upregulation in testis, and the amount of GR on miR-190b promoter regions of F0 males. In miR-190b-transfected Neuro 2a (N2a) cells, we demonstrated that miR-190b might directly bind to the 3'-UTR of brain-derived neurotrophic factor (BDNF). In the hippocampus of F1 males of CORT- or CMS-induced depressive-like models, increased miR-190b expression was accompanied by reduced BDNF and GR, which were ameliorated by cinnamaldehyde. In conclusion, cinnamaldehyde is a potential intervening agent for intergenerational inheritance of depression, probably by regulating GR/miR-190b/BDNF pathway.

Variation of the Vaginal Microbiome During and After Pregnancy in Chinese Women.

A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women. However, there is a lack of studies available on Chinese women. In the present study, the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequencing the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history, hypertensive disorders, delivery mode, and maternal age. Co-variation of 22 bacterial taxa, including the Lactobacillus genus and two of its species, may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes. In contrast, discriminant bacterial species were significantly different between women who had preterm birth (PTB) with and without premature rupture of membranes (PROM), and the community state type (CST) IV-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases, suggesting that specific bacterial species could be considered to distinguish between different types of PTB. By providing data on Chinese women, this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.

Monosialotetrahexosylganglioside in the treatment of chronic oxaliplatin-induced peripheral neurotoxicity: TJMUCH-GI-001, a randomised controlled trial.

BACKGROUND: Chronic oxaliplatin-induced peripheral neurotoxicity (OIPN) is the most troublesome and dose-limiting side effect of oxaliplatin. There is no effective treatment for chronic OIPN. We conducted a randomised controlled trial to investigate the efficacy of monosialotetrahexosylganglioside (GM1) in treating chronic OIPN. METHODS: In this single-centre, double-blind, phase Ⅲ trial, gastrointestinal cancer patients with persistent chronic OIPN were randomised in 1:1 ratio to receive either GM1 or placebo at Tianjin Medical University Cancer Institute and Hospital, China. GM1 was dosed at 60 mg daily for every 3 weeks or 40 mg daily for every 2 weeks. Seven- and fourteen- day infusions were administered to concurrent oxaliplatin users and oxaliplatin discontinuation patients, respectively. The primary endpoint was the relief of neurotoxicity (≥30% improvement), measured by a newly developed patient reported outcome measure (MCIPN) based on prior questionnaires including the European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy Induced Peripheral Neuropathy Questionnaire twenty-item scale. Visual analogue score (VAS) was used as another instrument for patients to evaluate the total Chronic OIPN treatment effect. VAS responders (≥30% improvement), double responders (≥30% improvement in both MCIPN and VAS), and high responders (≥50% improvement in the MCIPN total score) were also calculated. The secondary endpoints were safety and quality of life. The additional endpoints are progression-free survival (PFS), disease-free survival (DFS), overall survival (OS), and tumour response. (Trial registration number: NCT02486198 at ClinicalTrials.gov). FINDINGS: Between May 2015 to December 2017, 145 patients were randomly assigned to receive either GM1 (n=73) and placebo (n=72). Majority of the patients in both arms (90% in GM1 and 83% in placebo) continued receiving oxaliplatin on the trial. More patients responded in the GM1 group than in the placebo group (MCIPN responders: 53% vs 14%, VAS responders: 49% vs 22%, double responders: 41% vs 7%, and high responders: 32% vs 13%, all P < ·01). Analyses were also performed in concurrent oxaliplatin users. The results were consistent with those of the whole group. No deleterious effects of GM1 on survival or tumour response were found. There were no ≥G3 GM1-related adverse events. INTERPRETATION: In patients with chronic OIPN, the use of GM1 reduces the severity of chronic OIPN compared with placebo. FUNDING: This work was supported by clinical trial development fund of Tianjin Medical University Cancer Institute and Hospital (No.C1706).

Ultrastable Anode/Electrolyte Interface in Solid-State Lithium-Metal Batteries Using LiCux Nanowire Network Host.

High interfacial resistance and uncontrollable lithium (Li) dendrite are major challenges in solid-state Li-metal batteries (SSLMBs), as they lead to premature short-circuiting and failure of SSLMBs. Here, we report the synthesis of a composite anode comprising a three-dimensional LiCux nanowire network host infiltrated with Li (Li* anode) with low interfacial impedance and superior electrochemical performance. The Li* anode is fabricated by dissolving Cu foil into molten Li followed by solidification. The Li* anode exhibits good wettability with Li6.4La3Zr1.4Ta0.6O12 (LLZTO) and high mechanical strength, rendering low Li*/LLZTO interfacial impedance, homogeneous deposition of Li, and suppression of Li dendrites. Consequently, the Li* anode-based symmetric cells and full cells with LiNi0.88Co0.1Al0.02O2 (NCA), LiFePO4 (LFP), and FeF2 cathodes deliver remarkable electrochemical performance. Specifically, the Li*/LLZTO/Li* symmetrical cell achieves a remarkably long cycle lifetime of 10 000 h with 0.1 mA·cm-2; the Li*/LLZTO/NCA full cell maintains capacity retention of 73.4% after 500 cycles at 0.5C; and all-solid-state Li*/LLZTO/FeF2 full cell achieves a reversible capacity of 147 mAh·g-1 after 500 cycles at 100 mA·g-1. This work demonstrates potential design tactics for an ultrastable Li*/garnet interface to enable high-performance SSLMBs.

The Relationship between Prenatal Diagnosis Indications and Abnormal Chromosomal Karyotypes: A Retrospective Cohort of 4646 Cases in Beijing from 2012-2019.

BACKGROUND AND OBJECTIVE: Chromosomal abnormalities are one of the genetic disorders caused by abnormal chromosome number or structure and can endanger multiple organs, morphology and function of the systems in the human body. This study aims to investigate the relationship between prenatal diagnosis indications and abnormal karyotypes to improve prenatal screening. METHODS: The karyotype analyses were carried out on 4646 pregnant women with prenatal diagnosis indications referred to the first medical center of Chinese PLA General Hospital from 2012 to 2019. The incidence, distribution, and statistical features of chromosomal abnormality of different prenatal diagnosis indications were analyzed, and the relationships with the prenatal diagnosis indications were assessed. RESULTS: A total of 351 fetal chromosomal abnormalities were detected in 4646 karyotypes, with an incidence of 7.6%. The chromosomal abnormality incidence in the single indication group, two indications group, and three indications group was 5.8%, 16.1%, and 70.0%, respectively, indicating a statistically significant difference (p < 0.05). Advanced maternal age (AMA), high-risk maternal serum screening (MSS), and non-invasive prenatal DNA testing (NIPT) were the important indications for predicting abnormal karyotype. The number of prenatal diagnosis indications was highly correlated with fetal chromosomal abnormalities. The overall incidence of chromosomal abnormalities showed a tendency to increase with age. The incidence of Trisomy 21 was 3.2%, accounting for 42.5% of all chromosomal abnormalities, and the incidence tended to increase with maternal age. CONCLUSION: Prenatal karyotype analysis of pregnant women with prenatal diagnosis indications can effectively prevent the birth of defective children. AMA, MSS and NIPT were the important indications for predicting abnormal karyotype. In addition, the number of prenatal diagnosis indications is highly correlated with chromosomal abnormalities.

Combined exome sequencing and deep phenotyping in highly selected fetuses with skeletal dysplasia during the first and second trimesters improves diagnostic yield.

OBJECTIVE: To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES). METHOD: Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. The affected families underwent multiplatform genetic tests. RESULTS: Of the 27 affected fetuses, 21 (77.8%) had pathogenic or potential pathogenic variations in the following genes: COL1A1, FGFR3, COL2A1, COL1A2, FLNB, DYNC2LI1, and TRIP11. Two fetuses had compound heterozygous mutations in DYNC2LI1 and TRIP11, respectively, and the other 19 carried de novo autosomal dominant variants. Novel variants were identified in COL1A1, COL2A1, COL1A2, DYNC2LI1, and TRIP11 in 11 fetuses. We also included the first description of the phenotype of odontochondrodysplasia in a prenatal setting. CONCLUSIONS: ES or panel sequencing offers a high diagnostic yield for fetal skeletal dysplasia during the first and second trimesters. Comprehensive and complete phenotypic information is indispensable for genetic analysis and the expansion of genotype-phenotype correlations in fetal skeletal abnormalities.

Assessment of HCMV-encoded microRNAs in plasma as potential biomarkers in pregnant women with adverse pregnancy outcomes.

BACKGROUND: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections and can lead to adverse pregnancy outcomes (APOs). HCMV encodes multiple microRNAs (miRNAs) that have been reported to be partially related to host immune responses, cell cycle regulation, viral replication, and viral latency, and can be detected in human plasma. However, the relevance for HCMV-encoded miRNAs in maternal plasma as an indicator for APOs has never been evaluated. METHODS: Expression profiles of 22 HCMV-encoded miRNAs were first measured in plasma samples from 20 pregnant women with APOs and 28 normal controls using quantitative reverse-transcription polymerase chain reaction. Next, markedly changed miRNAs were validated in another independent validation set consisting of 20 pregnant women with APOs and 27 control subjects. Markedly changed miRNAs were further assessed in the placenta tissues. HCMV DNA in peripheral blood leukocytes (PBLs) and anti-HCMV immunoglobulin M (IgM) and anti-HCMV immunoglobulin G (IgG) in plasma were also examined in both training and validation sets. Diagnostic value and risk factors were compared between APO cohorts and normal controls. RESULTS: Analysis of the training and validation data sets revealed that plasma concentrations of hcmv-miR-UL148D, hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were significantly increased in pregnant women with APOs compared with normal controls. Hcmv-miR-US25-1-5p presented the largest area under the receiver-operating characteristic (ROC) curve (AUC) (0.735; 95% CI, 0.635-0.836), with a sensitivity of 68% and specificity of 71%. Furthermore, plasma levels of hcmv-miR-US25-1-5p and hcmv-miR-US5-1 correlated positively with APOs (P=0.029 and 0.035, respectively). Hcmv-miR-US25-1-5p in the placenta tissues were dramatically increased in APOs, and correlated with plasma hcmv-miR-US25-1-5p. Nevertheless, neither the concentration of HCMV DNA in PBLs nor the positivity rates of anti-HCMV IgM and anti-HCMV IgG in plasma showed a statistically significant correlation with APOs. CONCLUSIONS: We identified a unique signature of HCMV-encoded miRNAs in pregnant women with APOs that may be useful as a potential noninvasive biomarker for predicting and monitoring APOs during HCMV infection.

A nomogram for prediction of stage III/IV gastric cancer outcome after surgery: A multicenter population-based study.

Most patients with gastric cancer (GC) are first diagnosed at stage III-IV and surgery resection remains the primary therapeutic modality for these patients. However, clinical staging used for prediction of those patients provides limited information. We collected clinicopathological data and disease-progression information from 508 patients with stage III-IV GC at three Chinese hospitals and 1298 patients from the Surveillance, Epidemiology, and End Results database. Based on the stepwise multivariate regression model, we constructed a novel nomogram to predict overall survival (OS). The performance of discrimination for this model was measured using Harrell's concordance index (C-index) and receiver-operating characteristic curve (ROC), and was validated using calibration plots. Multivariate Cox regression analyses showed that tumor size, age at diagnosis, N stage, tumor grade, and distant metastases were outstanding independent prognostic factors of stage III-IV GC. We developed a nomogram based on these five prognostic predictors. In the training set, the C-index of the nomogram was 0.645 (95% CI: 0.611-0.679), which was higher than that of the American Joint Committee on Cancer TNM system alone (sixth TNM: 0.544; seventh TNM: 0.575; eighth TNM: 0.568). Similar results were observed in validation cohort. Moreover, calibration blots demonstrated good consistency between the actual and predicted OS probabilities. According to the nomogram, GC individuals could be classified into three groups (low-, middle-, and high-risk) (P < .001). Our nomogram complements the current staging system for prediction of individual prognosis with stage III-IV GC, and may be helpful for making individualized treatment decisions.

The c-Myc/miR-27b-3p/ATG10 regulatory axis regulates chemoresistance in colorectal cancer.

Oxaliplatin (OXA) resistance is the major obstacle to the anticancer effects of chemotherapy in colorectal cancer (CRC) patients. MicroRNAs (miRNAs) play an important role in the chemoresistance of various tumors. Our objective is to clarify the underlying mechanism of miRNAs in chemoresistance and provide a potential strategy to improve the response of CRC patients to chemotherapeutics. Methods: MiRNA microarray and Real-time PCR were performed to compare changes in miRNA expression between oxaliplatin-resistant and the parental cells. CCK8, apoptosis assay, immunofluorescence and xenograft studies were used to elucidate the impact of miR-27b-3p on regulating chemoresistance. Luciferase reporter assay and western blot were carried to assess the regulatory role of miR-27b-3p in ATG10 expression. The effects of miR-27b-3p and ATG10 on autophagy were investigated by GFP-LC3 fluorescence microscopy, transmission electron microscopy, and western blot. ChIP assay and luciferase assay were performed to test the c-Myc's occupancy on the miR-27B promoter. Results: We observed that miR-27b-3p expression was significantly downregulated in oxaliplatin-resistant cell lines (SW480-OxR and HCT116-OxR) compared to the corresponding parental cell lines and that miR-27b-3p expression was positively correlated with disease-free survival (DFS) time in colorectal cancer patients. MiR-27b-3p could sensitize colorectal cancer cells to oxaliplatin in vitro and in vivo. Under oxaliplatin treatment, chemoresistant cells showed a higher autophagy level than parental cells. Moreover, we also identified that miR-27b-3p inhibited the expression of ATG10 at the posttranscriptional level, thus inhibiting autophagy. Further study demonstrated that c-Myc can inhibit the expression of miR-27b-3p via binding to the promoter region of miR-27B gene. Conclusions: Our study identifies a novel c-Myc/miR-27b-3p/ATG10 signaling pathway that regulates colorectal cancer chemoresistance. These results suggest that miR-27b-3p is not only a potential indicator for evaluating efficiency of chemotherapy, but also a valuable therapeutic target for CRC, especially for patients with chemoresistance.

A unimolecular DNA fluorescent probe for determination of copper ions based on click chemistry.

A homogenous fluorescence method was constructed for Cu2+ detection by employing DNA-templated click chemistry and exonuclease reaction. In this strategy, a dumbbell shaped DNA probe, which contained an alkyne group and an azide group at its ends, was designed as the template for the click chemistry reaction, and also the signal probe. In the absence of Cu2+, the DNA probe was digested into small oligonucleotide fragments by exonuclease, resulting in a low fluorescence background. However, this DNA probe can be sealed at its two ends by Cu2+-induced click chemistry ligation in the presence of Cu2+. This closed structure of DNA would remain stable after addition of exonuclease, and could then be stained by SYBR Green I. A strong fluorescence signal was observed, which was related to the concentration of Cu2+. This assay showed high selectivity and reached the detection limit of 39 nM. Moreover, the proposed strategy exhibited satisfactory detection results in real complex sample analysis, and has promising application in environmental monitoring and food safety.

Control of mussel Mytilus galloprovincialis Lamarck fouling in water-cooling systems using plasma discharge.

To prevent marine macrofouling, the anti-fouling effect of liquid discharge on mussels Mytilus galloprovincialis Lamarck was investigated in a simulated water-cooling system. The effects of input energy, mussel distance from discharge center, continuous discharge time, and discharge energy distribution mode on mussel response (death or detachment) were systematically studied. The results showed that excellent anti-fouling effects could be achieved by increasing input energy, but the detachment rate and mortality of mussels decreased sharply when the mussels were farther away from the discharge center. Low frequency discharge for a long, continuous time and multiple stimuli at long intervals improved the anti-fouling effect. Shock waves are the most likely cause of mussel eradication, and the threshold values of peak pressure to prevent mussel settlement and to cause death were 0.02 MPa and 0.05 MPa, respectively.

Fucosyltransferase 8 deficiency suppresses breast cancer cell migration by interference of the FAK/integrin pathway.

BACKGROUND AND OBJECTIVE: Fucosyltranferase 8 (FUT8), which catalyzes core fucosylation of glycopeptides, plays important roles in cancer development. In this study, we aimed to explore the influence of FUT8 expression on migration ability of human breast cancer cells and its potential mechanisms. METHODS: The core fucosylation levels in normal and FUT8 deficient MCF-7 cells were analyzed by lectin LCA blots. Then, the cell adhesion assay, transwell and wound healing experiments were conducted. The phosphorylation of FAK and core fucosylation of E-cadherin and its downstream integrins in the FAK/integrin pathway were measured. Moreover, the expression levels of nuclear ß-catenin, MMP-2, and MMP-9 were also measured. RESULTS: The core fucosylation levels were significantly reduced by inhibited FUT8. FUT8 deficiency suppressed the adhesion, migration and invasion of MCF-7 cells; the potential mechanisms might involve three aspects. FUT8 deficiency inhibited FAK/integrin pathway by suppressing core fucosylation of E-cadherin. In addition, FUT8 deficiency reduced nuclear ß-catenin accumulation. The suppression of MMP-2 and MMP-9 expression also accounted for FUT8 deficiency inhibiting breast cancer cells migration. CONCLUSIONS: FUT8 deficiency suppressed migration of MCF-7 cells by impacting core fucosylation of E-cadherin and the downstream FAK/integrin pathway. Therefore, FUT8 is a potential biomarker for breast cancer detection and treatment.

Circular RNA circ_0008450 upregulates CXCL9 expression by targeting miR-577 to regulate cell proliferation and invasion in nasopharyngeal carcinoma.

As a kind of malignant tumor, nasopharyngeal carcinoma (NPC) has attracted increasing attention from researchers. As a member of the circular RNA (circRNA) family, circ_0008450 has been investigated in hepatocellular carcinoma but not in NPC. This study aims to reveal the special biologic role and mechanism of circ_0008450 in NPC. qRT-PCR analysis was conducted to test the level of circ_0008450 in different tissues and cells. Loss/Gain of function assay was utilized to detect the influence of silenced/overexpressed circ_0008450 on the proliferation, apoptosis, migration, and invasion of NPC cells. The mechanism of circ_0008450 was assessed by performing qRT-PCR and luciferase reporter experiments. The results showed that circ_0008450 was elevated in NPC tissues and cells. Silenced circ_0008450 could inhibit cell proliferation, and metastatic properties and increased the number of apoptotic cells. Ectopically expressed circ_0008450 strengthened the abovementioned malignant biological behaviors. Mechanistically, circ_0008450 reduced miR-577-mediated repression of CXCL9, resulting in facilitating the oncogenic functions of NPC. In conclusion, circ_0008450 acts as an oncogene in NPC cells through regulating miR-577/CXCL9 signaling. Our findings might provide a new therapeutic target for treating NPC.

miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly targeting IGF2BP2.

Pre-eclampsia is a pregnancy-related disease that may cause maternal, neonatal and fetal morbidity and mortality and exists in 3-5% of pregnancies worldwide. The discovery of dysregulated microRNAs and their roles in placental development has provided a new avenue for elucidating the mechanism involved in this pregnancy-specific disorder. Here, the roles of human miR-181a-5p, a microRNA that is increased in both the plasma and placenta of severe pre-eclamptic patients, in invasion and migration of trophoblasts were investigated. Ectopic-expression of miR-181a-5p impaired the invasion and migration of HTR-8/SVneo cells, whereas miR-181a-5p inhibition had the opposite effects. IGF2BP2, which harbors a highly conserved miR-181a-5p-binding site within its 3'-UTR, was identified to be directly inhibited by miR-181a-5p. Moreover, siRNAs targeting IGF2BP2 imitated the effects of overexpressed miR-181a-5p on HTR-8/SVneo cell invasion and migration, whereas restoring IGF2BP2 expression by overexpressing a plasmid encoding IGF2BP2 partially reversed the studied inhibitory functions of miR-181a-5p. Thus, we demonstrated here that miR-181a-5p suppresses the invasion and migration of cytotrophoblasts, and its inhibitory effects were at least partially mediated by the suppression of IGF2BP2 expression, thus shedding new light on the roles of miR-181a-5p in the pathogenesis of severe pre-eclampsia.

Effects of shock waves, ultraviolet light, and electric fields from pulsed discharges in water on inactivation of Escherichia coli.

In this work, the bacterial inactivation effects of shock waves, ultraviolet (UV) light, and electric field produced by high-voltage pulsed discharge in liquid with needle-plate configurations were studied. The contributions of each effect on the bacterial killing ratio in the discharge process were obtained individually by modifying reactor type and usage of glass, quartz, and black balloons. The results showed that the location from the discharge center axis significantly influenced the effects of shock waves and electric fields, although the effect of UV light was not affected by the location in the reactor. The effects of shock waves and electric fields were improved by decreasing the distance from the discharge center axis. Under this experimental condition, the effects of shock waves, UV light, and electric fields produced by discharges on bacterial inactivation were approximately 36.1%, 30.8%, 12.7%, respectively. Other contributions seemed to be due to activated species.

Preferential selection and transfer of euploid noncarrier embryos in preimplantation genetic diagnosis cycles for reciprocal translocations.

OBJECTIVE: To develop and validate a new strategy to distinguish between balanced/euploid carrier and noncarrier embryos in preimplantation genetic diagnosis (PGD) cycles for reciprocal translocations and to successfully achieve a live birth after selective transfer of a noncarrier embryo. DESIGN: Retrospective and prospective study. SETTING: In vitro fertilization (IVF) units. PATIENT(S): Eleven patients undergoing mate pair sequencing for identification of translocation breakpoints, followed by clinical PGD cycles. INTERVENTION(S): Embryo biopsy with 24-chromosome testing to determine carrier status of balanced/euploid embryos. MAIN OUTCOME MEASURE(S): Definition of translocation breakpoints and polymerase chain reaction (PCR) diagnostic primers, correct diagnosis of euploid embryos for carrier status, and a live birth with a normal karyotype after transfer of a noncarrier embryo. RESULT(S): In 9 of 11 patients (82%), translocation breakpoints were successfully identified. In four patients with a term PGD pregnancy established with a balanced/euploid embryo of unknown carrier status, the correct carrier status was retrospectively determined, matching with the cytogenetic karyotype of the resulting newborns. In a prospective PGD cycle undertaken by a patient with a 46,XY,t(7;14)(q22;q24.3) translocation, the four balanced/euploid embryos identified comprised three carriers and one noncarrier. Transfer of the noncarrier embryo resulted in birth of a healthy girl who was subsequently confirmed with a normal 46,XX karyotype. CONCLUSION(S): The combination of mate pair sequencing and PCR breakpoint analysis of balanced reciprocal translocation derivatives is a novel, reliable, and accurate strategy for distinguishing between carrier and noncarrier balanced/euploid embryos. The method has potential application in clinical PGD cycles for patients with reciprocal translocations or other structural rearrangements.