A novel variation in DEPDC5 causing familial focal epilepsy with variable foci.

Background: Disheveled, EGL-10, and pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a component of GTPase-activating protein (GAP) activity toward the RAG complex 1 (GATOR1) protein, which is an inhibitor of the amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). With the wide application of whole exome sequencing (WES), more and more variations in DEPDC5 were uncovered in FFEVF families. Methods: A family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation. Results: A novel variant, c.1217 + 2T>A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5' end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF. Conclusion: The results suggest that c.1217 + 2T>A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.

Morphological quality on Day 3 affects the pregnancy outcomes of low-quality euploid blastocysts: a retrospective cohort study.

STUDY QUESTION: Does the morphological quality on Day 3 influence the pregnancy outcomes of euploid blastocysts? SUMMARY ANSWER: The morphological quality on Day 3 affects the clinical pregnancy rate (CPR) and live birth rate (LBR) of low-quality euploid blastocysts. WHAT IS KNOWN ALREADY: The morphological grading of Day 3 embryos affects the pregnancy outcome of cleavage-stage embryos and is an excellent indicator to predict embryo development potential. However, it is still unclear whether morphological quality on Day 3 is associated with pregnancy outcomes of the euploid blastocyst. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study comprised 1275 patients who received single euploid blastocyst transfer between January 2016 and August 2021 at a tertiary teaching hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were grouped into two groups according to the morphological grading on Day 3 of transferred blastocysts: high-quality (HQ, including Grades I and II) Day 3 embryos and low-quality (LQ, Grade III) Day 3 embryos. The primary outcomes were CPR and LBR. Interactions of development days (Day 5 and Day 6) and morphological quality (high- and low-quality) of blastocysts with morphological quality of Day 3 embryos on pregnancy outcomes were tested in the stratified analysis and logistic regression models. The multivariate logistic regression analysis was conducted to investigate the independent effect of the morphological quality of Day 3 embryos on pregnancy outcomes after adjusting for potentially confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: The CPR and LBR of the HQ Day 3 embryos group were statistically higher than those of the LQ Day 3 embryos group (CPR: 59.73% versus 49.70%, respectively, P = 0.015; LBR: 49.73% versus 41.21%, respectively, P = 0.041). The development days of blastocysts did not exhibit a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.648) and LBR (P for interaction = 0.925). The morphological quality of blastocysts exhibits a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.020) and LBR (P for interaction = 0.012). After adjusting for potential confounders, the HQ Day 3 embryo group was positively associated with the CPR (adjusted odds ratio (aOR): 2.10, 95% CI: 1.31-3.36, P = 0.002) and LBR (aOR: 1.97, 95% CI: 1.20-3.25, P = 0.008) of LQ blastocysts. However, the morphological quality on Day 3 was not significantly associated with the CPR (aOR: 0.95, 95% CI: 0.58-1.55, P = 0.835) and LBR (aOR: 0.86, 95% CI: 0.53-1.40, P = 0.550) of HQ blastocysts. LIMITATIONS, REASONS FOR CAUTION: Selection and confounding bias introduced by the retrospective design cannot be completely eliminated in this study, although multivariable logistic analysis was conducted to adjust for potential confounders. Also, some subgroups had small sample sizes, which may reduce statistical power. Moreover, participants in our study only received single euploid blastocyst transfer, and whether the results could apply to blastocysts with unknown ploidy status is unclear. WIDER IMPLICATIONS OF THE FINDINGS: This study found that the morphological quality on Day 3 was significantly associated with the CPR and LBR of LQ blastocysts; Therefore, when only LQ euploid blastocysts are available for transfer, blastocysts derived from HQ Day 3 embryos are recommended. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Bioinspired Colorimetric Double Inverse Opal Photonic Crystal Indicators for Ethanol Concentration Sensing in Fermentation Engineering.

Photonic crystal-based ethanol concentration indicators with rapid response and brilliant structural color output definitely take a place in colorimetric sensors. Here, based on the H-bond-regulated swelling of acrylate shape memory polymers (SMPs) and the solvent-induced structural color change of the double inverse opal photonic crystals (DIOPCs), new-type photonic crystals (PCs) colorimetric indicators were constructed, exhibiting a span of maximum reflection wavelength (λmax) up to ∼166 nm in response to alcohols with concentrations from 0 to 100 vol %. DIOPC indicators (DIOPCIs) show a rapid response to alcohols (<1.5 s) and output different structural colors (covering from blue to red). The colorimetric sensing mechanism includes the solvent-triggered recovery of the inverse opal skeleton, the cosolvency effect and H-bonds induced swelling/shrinkage of the polymer, the phase separation between polystyrene (PS) microsphere and polymer skeleton, and the light diffraction of DIOPCs. While ensuring a larger λmax span by regulating the H-bond interactions in polymer chains through acrylamide (AAm), AAm-modified DIOPCIs are sensitive to some specific ethanol concentrations. The real-time sensing of ethanol concentration during fermentation verified the practicability of DIOPCIs, thus establishing a visual model between structural color and corresponding fermentation kinetics. We envisage that the DIOPCIs will contribute to the intelligentization of the alcoholic fermentation and distillation industry.

Residue-Free and Recyclable Starch-Based Flocculants for Dye Wastewater Flocculation.

Flocculants are crucial agents in wastewater treatment because they can remove oppositely charged impurities effectively and swiftly. However, flocculation also inevitably causes secondary contamination due to the residual properties, nonreusability, and nondegradability of traditional flocculant molecules. Herein, an ecofriendly starch-based flocculant, i.e., 2,4-bis(dimethylamino)-[1,3,5]-triazine-6-starch, was synthesized via a preactivation-etherification strategy. The large molecular weight property of the flocculant produced by this method enhances the intermolecular hydrophobic association, achieving complete phase separation of all flocculant molecules from water and residue-free flocculation for the first time. Importantly, a large molecular weight tertiary amine starch-based flocculant (LMTS) exhibits a remarkable flocculation capacity of over 1800 mg·g-1 for dye wastewater, which is significantly higher than that of traditional polyacrylamide and polyaluminum chloride flocculants. Furthermore, the LMTS flocculant could be recycled by pH adjustment, and its structural stability ensured sustained reusability. This high-performance residue-free biomass-based flocculant offers a green advance for wastewater treatment.

The preimplantation genetic testing for monogenic disorders strategy for blocking the transmission of hereditary cancers through haplotype linkage analysis by karyomapping.

PURPOSE: Providing feasible preimplantation genetic testing strategies for monogenic disorders (PGT-M) for prevention and control of genetic cancers. METHODS: Inclusion of families with a specific pathogenic mutation or a clear family history of genetic cancers. Identification of the distribution of hereditary cancer-related mutations in families through genetic testing. After a series of assisted reproductive measures such as down-regulation, stimulation, egg retrieval, and in vitro fertilization, a biopsy of trophectoderm cells from a blastocyst was performed for single-cell level whole-genome amplification (WGA). Then, the detection of chromosomal aneuploidies was performed by karyomapping. Construction of a haplotype-based linkage analysis to determine whether the embryo carries the mutation. Meanwhile, we performed CNV testing. Finally, embryos can be selected for transfer, and the results will be verified in 18-22 weeks after pregnancy. RESULTS: Six couples with a total of 7 cycles were included in our study. Except for cycle 1 of case 5 which did not result in a transferable embryo, the remaining 6 cycles produced transferable embryos and had a successful pregnancy. Four couples have had amniotic fluid tests to confirm that the fetus does not carry the mutation, while 1 couple was not tested due to insufficient pregnancy weeks. And the remaining couples had to induce labor due to fetal megacystis during pregnancy. CONCLUSION: Our strategy has been proven to be feasible. It can effectively prevent transmission of hereditary cancer-related mutations to offspring during the prenatal stage.

Generation of a human haploid neural stem cell line for genome-wide genetic screening.

BACKGROUND: Haploid embryonic stem cells (haESCs) have been established in many species. Differentiated haploid cell line types in mammals are lacking due to spontaneous diploidization during differentiation that compromises lineage-specific screens. AIM: To derive human haploid neural stem cells (haNSCs) to carry out lineage-specific screens. METHODS: Human haNSCs were differentiated from human extended haESCs with the help of Y27632 (ROCK signaling pathway inhibitor) and a series of cytokines to reduce diploidization. Neuronal differentiation of haNSCs was performed to examine their neural differentiation potency. Global gene expression analysis was con-ducted to compare haNSCs with diploid NSCs and haESCs. Fluorescence activated cell sorting was performed to assess the diploidization rate of extended haESCs and haNSCs. Genetic manipulation and screening were utilized to evaluate the significance of human haNSCs as genetic screening tools. RESULTS: Human haESCs in extended pluripotent culture medium showed more compact and smaller colonies, a higher efficiency in neural differentiation, a higher cell survival ratio and higher stability in haploidy maintenance. These characteristics effectively facilitated the derivation of human haNSCs. These human haNSCs can be generated by differentiation and maintain haploidy and multipotency to neurons and glia in the long term in vitro. After PiggyBac transfection, there were multiple insertion sites in the human haNSCs' genome, and the insertion sites were evenly spread across all chromosomes. In addition, after the cells were treated with manganese, we were able to generate a list of manganese-induced toxicity genes, demonstrating their utility as genetic screening tools. CONCLUSION: This is the first report of a generated human haploid somatic cell line with a complete genome, proliferative ability and neural differentiation potential that provides cell resources for recessive inheritance and drug targeted screening.

Identification of carrier status of Xp22.31 microdeletions associated with X-linked ichthyosis at the single-cell level using haplotype linkage analysis by karyomapping.

PURPOSE: Currently, owing to the limitations of high-throughput sequencing depth and the allele dropout caused by the whole-genome amplification, detection of chromosomal variants in embryos with CNVs <5 Mb is unsatisfactory at the single-cell level using only conventional sequencing methods. Therefore, here we aimed to use a strategy of preimplantation genetic testing for monogenic (PGT-M) to compensate for the shortcomings of conventional sequencing methods. The purpose of this study is to report the effectiveness of haplotype linkage analysis by karyomapping for preimplantation diagnosis microdeletion diseases. METHODS: Six couples carrying chromosomal microdeletions associated with X-linked ichthyosis were recruited, and all couples entered the PGT process. Multiple displacement amplification (MDA) method was used to amplify the whole-genome DNA of trophectoderm cells. Then karyomapping based on single nucleotide polymorphism (SNP) was used for haplotype linkage analysis to detect alleles carrying microdeletions, and CNVs of embryos were identified to determine euploid identity. Amniotic fluid tests were performed in the second trimester to verify the PGT-M results. RESULTS: All couples were tested for chromosomal microdeletions, with deletion fragments ranging in size from 1.60 to 1.73 Mb, and one partner in each couple did not carry the microdeletion. Three couples successfully underwent PGT-M assisted conception and obtained healthy live births. CONCLUSION: This study shows that haplotype linkage analysis by karyomapping could effectively detect the carrier status of embryos with microdeletions at the single-cell level. This approach may be applied to the preimplantation diagnosis of various chromosomal microvariation diseases.

The reference value of anti-Müllerian hormone to diagnose polycystic ovary syndrome is inversely associated with BMI: a retrospective study.

BACKGROUND: This study aimed to evaluate the cut-off value of anti-Müllerian hormone (AMH) combined with body mass index (BMI) in the diagnosis of polycystic ovary syndrome (PCOS) and polycystic ovary morphology (PCOM). METHODS: This retrospective study included 15,970 patients: 3775 women with PCOS, 2879 women with PCOM, and 9316 patients as controls. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for AMH. We randomly divided the patients into two data sets. In dataset 1, a receiver operating characteristic (ROC) curve was generated to analyze the accuracy of basic AMH levels in diagnosing PCOS and PCOM. The optimal cut-off value was calculated in dataset 1 and validated in dataset 2, expressed as sensitivity and specificity. RESULTS: In the PCOS group, obese patients had the lowest AMH levels, while underweight patients had the highest AMH level (P < 0.001). After adjusting for age, the ratio of luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone level, and BMI, AMH was an independent predictor of PCOS and PCOM. In the group with BMI < 18.5 kg/m2, the optimistic AMH cut-off value was 5.145 ng/mL with a sensitivity of 84.3% and specificity of 89.1%, whereas in the BMI ≥ 28 kg/m2 group, the optimistic AMH cut-off value was 3.165 ng/mL with a sensitivity of 88.7% and specificity of 74.6%. For the BMI range categories of 18.5-24, 24.0-28 kg/m2, the optimistic AMH cut-off values were 4.345 ng/mL and 4.115 ng/mL, respectively. The tendency that the group with lower weight corresponded to higher AMH cut-off values was also applicable to PCOM. In the same BMI category, patients with PCOM had a lower AMH diagnosis threshold than those with PCOS (< 18.5 kg/m2, 5.145 vs. 4.3 ng/mL; 18.5-24 kg/m2, 4.345 vs. 3.635 ng/mL; 24.0-28 kg/m2, 4.115 vs. 3.73 ng/mL; ≥ 28 kg /m2, 3.165 vs. 3.155 ng/mL). These cut-off values had a good diagnostic efficacy in the validation dataset. Based on different phenotypes and severity of ovulation disorders, the distribution of AMH in PCOS were also significantly different (P < 0.001). CONCLUSIONS: AMH is a potential diagnostic indicator of PCOS and is adversely associated with BMI. The AMH cut-off value for diagnosing PCOS was significantly higher than that for PCOM.

Heterogeneous Structural Color Conductive Photonic Organohydrogel Fibers with Alternating Single and Dual Networks.

Intelligent interactive electronic devices can dynamically respond to and visualize various stimuli, promoting the rapid development of flexible electronics. In this paper, an alternating single- and dual-network design strategy was developed for ingeniously constructing an interactive electronic fiber sensor with heterogeneous structural color (HSCEF sensor). The resulting sensor can rapidly output the synchronous electrical and optical dual signals under strain by adjusting the transport distance of conductive ions and the lattice spacing of the photonic crystal (∼200 ms). Meanwhile, the addition of low-freezing-point glycerol endowed the HSCEF sensor with excellent low-temperature tolerance (-25 °C) and cyclic stability. Notably, benefiting from the alternating single- and dual-network structure, the HSCEF sensor exhibits attractive heterogeneous structural color, which achieves colorimetric changes in the full visible light region with high mechanochromic sensitivity (2.25 nm %-1) and large wavelength shift (Δλ ∼ 225 nm). An intelligent wearable interactive sensor is finally used for real-time dynamic detection of joint movements, realizing precise resolution of different amplitudes. This work provides a general strategy to transform conventional photonic gels into heterogeneous structural color ones, and the developed new interactive sensor with rich optical information could be further used for visual health and exercise monitoring, intelligent soft robotics, wearable sensors, etc.

miR-188-3p-targeted regulation of ATG7 affects cell autophagy in patients with nonobstructive azoospermia.

BACKGROUND: Nonobstructive azoospermia (NOA) is one of the most difficult forms of male infertility to treat, and its pathogenesis is still unclear. miRNAs can regulate autophagy by affecting their target gene expression. Our previous study found that miR-188-3p expression in NOA patients was low. There are potential binding sites between the autophagy gene ATG7 and miR-188-3p. This study aimed to verify the binding site between miR-188-3p and ATG7 and whether miR-188-3p affects autophagy and participates in NOA by regulating ATG7 to influence the autophagy marker genes LC3 and Beclin-1. METHODS: Testicular tissue from 16 NOA patients and 16 patients with normal spermatogenesis and 5 cases in each group of pathological sections were collected. High-throughput sequencing was performed to detect mRNA expression differences. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunohistochemical staining and immunofluorescence were used to detect protein localization and expression. Autophagosome changes were detected by electron microscopy. The targeting relationship between miR-188-3p and ATG7 was confirmed by a luciferase assay. RESULTS: ATG7 protein was localized in the cytoplasm of spermatogenic cells at all levels, and the ATG7 gene (p = 0.019) and protein (p = 0.000) were more highly expressed in the NOA group. ATG7 expression after overexpression/inhibition of miR-188-3p was significantly lower (p = 0.029)/higher (p = 0.021) than in the control group. After overexpression of miR-188-3p, the ATG7 3'UTR-WT luciferase activity was impeded (p = 0.004), while the ATG7 3'UTR-MUT luciferase activity showed no significant difference (p = 0.46). LC3 (p = 0.023) and Beclin-1 (p = 0.041) expression in the NOA group was significantly higher. LC3 and Beclin-1 gene expression after miR-188-3p overexpression/inhibition was significantly lower (p = 0.010 and 0.024, respectively) and higher (p = 0.024 and 0.049, respectively). LC3 punctate aggregation in the cytoplasm decreased after overexpression of miR-188-3p, while the LC3 punctate aggregation in the miR-188-3p inhibitor group was higher. The number of autophagosomes in the miR-188-3p mimic group was lower than the number of autophagosomes in the mimic NC group. CONCLUSIONS: LC3 and Beclin-1 were more highly expressed in NOA testes and negatively correlated with the expression of miR-188-3p, suggesting that miR-188-3p may be involved in the process of autophagy in NOA. miR-188-3p may regulate its target gene ATG7 to participate in autophagy anDual luciferase experiment d affect the development of NOA.

The hospitalization burden of all-cause pneumonia in China: A population-based study, 2009-2017.

Background: Pneumonia represents a public health problem of substantial health and economic burden. However, the evidence on the burden of adult pneumonia is limited in China. Methods: The China Kadoorie Biobank recruited 512,725 participants aged 30-79 years from five urban and five rural areas during 2004-2008. The current analyses included 506,086 participants who were alive in 2009. Pneumonia hospitalizations were ascertained through the health insurance system until December 31, 2017. Generalized linear models were used to examine the secular trends and regional and population variations in pneumonia hospitalization rate, mean length of hospital stay (LOS), and 30-day case fatality rate (CFR). Findings: A total of 27,879 participants with 36,567 pneumonia hospitalizations were identified with a mean follow-up time of 8·9 years. The unadjusted hospitalization rate was 8·4 (95% confidence interval [CI]: 8·3, 8·6) per 1000 person-years, with an increase of 15·5% annually from 4·2 (3·9, 4·4) in 2009 to 10·9 (10·6, 11·3) in 2017, after adjusting for age, sex, study area. The mean LOS was 8·8 (95% CI: 8·7, 8·9) days, with a slight decrease of 1·0% annually from 2009 to 2017. The average 30-day CFR remained practically unchanged at 2·4 (95% CI: 2·2, 2·5) deaths per 100 admissions. A clear seasonal pattern of pneumonia hospitalization rate was observed, and the hospitalization rate and CFR differed across regions and subpopulations of different ages and underlying conditions. Interpretation: There was an increasing hospitalization burden of pneumonia in Chinese adults, especially for adults aged ≥60 years or those with underlying conditions. Funding: The National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key R&D Program of China, the Chinese Ministry of Science and Technology. Translated abstract in Chinese: This translation in Chinese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. :, ., .:(China Kadoorie Biobank)2004-2008555030-79.506,086200911.20091120171231.,30,.:8.9, 27,879, 36,567.8.4 (95% CI:8.3, 8.6)/1000, ,, 20094.2 (3.9, 4.4)201710.9 (10.6, 11.3), 15.5%.8.8(95% CI:8.7, 8.9), 1.0%.30, 2.4(95% CI:2.2, 2.5)/100.;,, 30.:, ≥60.

Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest.

Background: Oocyte maturation arrest is a disease that produces immature oocytes and cannot be mature after culturing in vitro, which leads to female primary infertility. We aimed to summarize nine representative patients in our center to retrospectively analyze the genetic variants and clinical characteristics of oocyte maturation arrest. Methods: This study examined and analyzed nine families with oocyte maturation arrest. Whole-exome sequencing (WES) of the probands was performed to detect the pathogenic variants. Sanger sequencing verified the WES findings in patients and available parents. ExAC database was used to search the variant frequency. The variants were assessed by pathogenicity and conservational property prediction analysis and according to the American College of Medical Genetics and Genomics (ACMG). Phenotypes of oocytes were evaluated by a light microscopy, and the phenotype-genotype correlation was also evaluated. Results: Nine pathogenic variants in five genes were detected in nine patients, of which three were novel variants, including PATL2 [c.1374A > G (p. Ile458Met)] and [1289-1291del TCC (p. Leu430del)] and ZP2 [c.1543C > T (p. Pro515Ser)]. Nine variants were predicted to be pathogenic, resulting in different types of oocyte maturation arrest and clinical phenotypes. Conclusion: Three novel pathogenic variants were identified, enabling the expansion of the gene variant spectrum. The related pathogenic mutations of the PATL2, TUBB8, and ZP1∼3 genes were highly suggestive of being causative of oocyte maturation arrest.

Biomimetic Janus photonic soft actuator with structural color self-reporting.

Soft actuators with variable signal/color play an important role in the fields of targeted locomotion, artificial phototropism, drug screening, cargo transportation, and interactive sensing. The ability to achieve rapid response, large curvature, wide bending angle, and full-color display continues to be an unresolved challenge for artificial actuating materials. Inspired by the angle-dependent structural color of broad-tailed hummingbird and the Janus wettability of the lotus leaf, a Janus photonic soft actuator (JPSA) was fabricated by integrating an underwater super-oleophilic copper micro-nano array and oil-phobic inverse opal through a Laplace channel. The JPSA exhibits unidirectional permeability to underwater oil droplets. Attractively, with the combination of a swellable super-oleophilic surface and photonic crystals, JPSAs were endowed with oil-controlled reversible bending behavior with self-reporting angle-dependent color indication. We described for the first time the directional actuating mechanism induced by underwater oil unidirectional penetration and revealed the corresponding actuating kinetics and the inner-stress distribution/transfer by using structural color. As an extension of such theory, a rapid responsive JPSA with a wide bending angle and full-color self-reporting is further fabricated. This work provides an efficient strategy for oil directional transportation and separation in aqueous media and inspires the fabrication of a soft actuator/sensor with structural color self-reporting.

Correlation study of male semen parameters and embryo aneuploidy in preimplantation genetic testing for aneuploidy.

Objective: The purpose of this study was to evaluate the influence of abnormal semen parameters on embryo aneuploidy based on single nucleotide polymorphism microarray (SNP array). Methods: A total of 464 blastocysts from 103 PGT-A cycles were analyzed. The embryo quality and embryo aneuploidy rates were compared between different groups which divided by male semen parameters (sperm concentration, motility, morphology, and DFI) according the WHO criteria (2021). Results: The total blastocysts chromosome aneuploidy rate was 42.3% (191/452). In the teratozoospermia group, the good-quality embryo and blastocyst formation rate were lower than the normal group(44.4% vs 60.7%, P <0.01; 33.3% vs 43.5%, P <0.05), The good-quality embryo rate in normal DFI group was significantly higher than high-DFI group (59.0% vs 48.4%, P < 0.05). The blastocyst aneuploidy rate in low sperm concentration group, and high DFI group was no differences between with that in normal sperm concentration and DFI group (47.7% vs 37.8% and 44.7% vs 37.8%, P>0.05). The aneuploid rate of blastocyst in teratozoospermic and asthenozoospermia group was significantly higher than that of normal morphology and motility group (50.0% vs 34.0% and 46.7% vs 33.7%, P<0.05). Conclusion: Our study revealed that sperm DFI were positively correlated with blastocyst aneuploidy rate, while sperm motility and sperm morphology rate were negatively correlated with blastocyst aneuploidy rate. Abnormal semen parameters may affect embryo quality and increase the aneuploidy rate of blastocyst chromosomes, suggesting that in clinical practice of assisted reproduction patients with abnormal semen parameters can be treated in advance to improve sperm quality, so as to reduce the impact on embryo quality and achieve a better pregnancy outcome.

[Preimplantation genetic testing for a couple where the husband is affected by osteogenesis imperfecta combined with balanced translocation using karyomapping technique].

OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a couple where the husband was affected by osteogenesis imperfecta combined with balanced translocation using the karyomapping technique. METHODS: Blastocysts were detected using karyomapping, the carrier status of COL1A1 c.760G>A (p.Gly254Arg) variant and the carrier status of the translocated chromosome were analyzed simultaneously. RESULTS: For a total of 10 blastocysts, two euploid blastocysts were found to not carry the COL1A1 c.760G>A (p.Gly254Arg) variant but a balanced translocation. After transplanting one of the blastocysts, clinical pregnancy was achieved. Amniocentesis at 18th gestational week and prenatal genetic testing was in keeping with the result of PGT.A healthy female was born at 40+4 weeks gestation. CONCLUSION: For patients simultaneously carrying genetic variant and balanced chromosomal translocation, PGT can be performed with efficiency by the use of karyomapping method.

Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study.

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

Calcium Ionophore (A23187) Rescues the Activation of Unfertilized Oocytes After Intracytoplasmic Sperm Injection and Chromosome Analysis of Blastocyst After Activation.

Calcium is a crucial factor in regulating the biological behavior of cells. The imbalance of calcium homeostasis in cytoplasm will cause abnormal behavior of cells and the occurrence of diseases. In intracytoplasmic sperm injection (ICSI) cycle, the dysfunction of oocyte activation caused by insufficient release of Ca2+ from endoplasmic reticulum is one of the main reasons for repeated fertilization failure. Calcium ionophore (A23187) is a highly selective calcium ionophore, which can form stable complex with Ca2+ and pass through the cell membrane at will, effectively increasing intracellular Ca2+ levels. It has been reported that calcium ionophore (A23187) can activate oocytes and obtain normal embryos. However, there are few studies on unfertilized oocytes after calcium ionophore (A23187) rescue activation in ICSI cycle. The purpose of this study was to analyze the effects of calcium ionophore (A23187) rescue activation on the activation of unfertilized oocytes, embryonic development potential, embryonic development timing and chromosomal aneuploidy, and to compare and analyze the clinical data of patients with calcium ionophore (A23187) activation in clinical application. The results showed that a certain proportion of high-quality blastocysts with normal karyotype could be obtained after calcium ionophore (A23187) rescue activation of unfertilized oocytes, and it did not have a significant effect on the timing of embryo development. In clinical practice, direct activation with calcium ionophore (A23187) after ICSI was better than rescue activation the next day. In conclusions, the studies on the effectiveness and safety of calcium ionophore (A23187) rescue activation for oocytes with ICSI fertilization failure can enable some patients to obtain usable, high-quality embryos during the first ICSI cycle.

[Up-regulated SUMO1 expression by inhibition of miRNA-548m as a potential cause of congenital orofacial cleft in a fetus].

OBJECTIVE: To explore the genetic etiology for a fetus with congenital orofacial cleft. METHODS: Single nucleotide polymorphism microarray (SNP array) was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation (CNVs). Pathogenicity of the candidate gene was validated through experiment. RESULTS: SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91 063 807-100 293 555), which was inherited from its mother. The region contained 13 OMIM genes and 1 ncRNA coding gene(MIR548M). Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft. CONCLUSION: Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.

Parental methylome reprogramming in human uniparental blastocysts reveals germline memory transition.

Uniparental embryos derived from only the mother (gynogenetic [GG]) or the father (androgenetic [AG]) are unique models for studying genomic imprinting and parental contributions to embryonic development. Human parthenogenetic embryos can be obtained following artificial activation of unfertilized oocytes, but the production of AG embryos by injection of two sperm into one denucleated oocyte leads to an extra centriole, resulting in multipolar spindles, abnormal cell division, and developmental defects. Here, we improved androgenote production by transferring the male pronucleus from one zygote into another haploid androgenote to prevent extra centrioles and successfully generated human diploid AG embryos capable of developing into blastocysts with an identifiable inner cell mass (ICM) and trophectoderm (TE). The GG embryos were also generated. The zygotic genome was successfully activated in both the AG and GG embryos. DNA methylome analysis showed that the GG blastocysts partially retain the oocyte transcription-dependent methylation pattern, whereas the AG blastocyst methylome showed more extensive demethylation. The methylation states of most known imprinted differentially methylated regions (DMRs) were recapitulated in the AG and GG blastocysts. Novel candidate imprinted DMRs were also identified. The production of uniparental human embryos followed by transcriptome and methylome analysis is valuable for identifying parental contributions and epigenome memory transitions during early human development.

Lotus Seedpod Inspiration: Particle-Nested Double-Inverse Opal Films with Fast and Reversible Structural Color Switching for Information Security.

The integration of novel structures into colloidal crystals provides the possibility of constructing stimuli-responsive photonic materials. However, in most opal and inverse opal structures, replacing the interior air with an infiltrated liquid will cause partial refractive index matching, resulting in the reduction or even disappearance of the photonic band gap. Herein, inspired by the lotus seedpod, an innovative particle-nested double-inverse opal film with fast and reversible structural color switching (≈1 s) is first fabricated by introducing polystyrene (PS) spheres into an inverted opal backbone. Importantly, refractive index matching can be effectively avoided due to the existence of internal PS spheres, and optical switching from diffusive to photonic behavior is achieved by a liquid with low surface tension for the response. Furthermore, a reversible ethanol stimuli-response bilayer double-inverse opal film with multistate switching for information encryption is proposed by combining optical scattering and diffraction. The scattered light from the top layer caused by the randomly distributed and weakly scattering PS spheres within the pores makes the pattern at the bottom invisible. Simultaneously, the display and discoloration of the pattern can be realized instantaneously by ethanol response. Thus, this new preparation strategy exhibits great potential in the security fields.