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Premature ovarian insufficiency (POI) is the main cause of infertility in women. Some cases of POI are thought to be caused by genetic defects and the clinical outcomes of these patients are unknown. Here, we performed whole-exome sequencing of the peripheral blood of a cohort of 55 subjects with POI and identified one heterozygous missense variant in FOXL2 (c.1045G>C; p.Arg349Gly) and two heterozygous missense variants in ERCC6 (c.379G>A; p.Val127Ile and c.4223A>C; p.Glu1408 Ala) in four POI patients. All of these heterozygous mutations were predicted to be deleterious and were parentally inherited from their heterozygous fathers. The mRNA and protein expression of FOXL2 and ERCC6 were absent or decreased in the patients. The patients carrying the variants of FOXL2 (c.1045G>C; p.Arg349Gly) and ERCC6 (c.379G>A; p.Val127Ile) failed to conceive in two and four assisted reproductive cycles, respectively. Another patient and her sister carrying the ERCC6 (c.4223A>C; p.Glu1408 Ala) variant achieved good clinical outcomes after assisted reproductive therapy. Our findings support the possible roles of FOXL2 and ERCC6 in POI and might contribute to the genetic counseling of POI patients.

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BACKGROUND: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. METHODS: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. RESULTS: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

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The application of semiconductor photocatalysts in wastewater treatment always has a drawback, which is the lack of selectivity for pollutants, but molecular imprinting technology (MIT) is a remarkable method for preparing highly selective adsorbents for low concentration target pollutants. Up to now, the research of molecular imprinting materials has mainly focused on organic polymers, and there has been little research on inorganic molecular imprinting materials. In the present work, we introduced carbon quantum dots (CQDs) into the flower-like hierarchical ZnO to prepare photocatalysts CQDs/ZnO. Further, with ciprofloxacin (CIP) as the template molecule, a molecular imprinting material MIP-CQDs/ZnO1-x was prepared by introducing both oxygen vacancies and imprinted cavities into CQDs/ZnO by the hydrothermal calcination method. It can not only increase the concentration of oxygen vacancies and broaden the light absorption range of zinc oxide without changing the crystal form of ZnO but also make it have the characteristics of preferential adsorption and degradation of CIP during the degradation process. Under the synergistic effect of CQDs, oxygen vacancies, and molecularly imprinted cavities, the molecularly imprinted material exhibits excellent photocatalytic and selective adsorption performance.

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To meet the packaging requirements of sapphire in special electronic components, there is an urgent need for a joining process that can realize a good connection between sapphire and dissimilar metals at a low temperature. In this work, the surface of a sapphire substrate was successfully catalytically activated and metallized by an electroless nickel plating process. Moreover, the solderability and interconnection of metallized sapphire with Sn-based solders were evaluated and investigated at 250 °C, and the wetting angle of the Sn-based solders on sapphire on sapphire without and with metallization was 125° and 51°, respectively. The interfacial microscopic morphology and element distribution in the Cu/Sn-Ag solder/sapphire solder joints were analyzed. It was found that the middle solder layer has diffused during the reflow process, inferring good adhesion between sapphire and Cu substrate with the aid of the Ni-P deposition. Thus, a sapphire welding method with a simple process suitable for practical applications is demonstrated.

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OBJECTIVE: To explore the effect of autophagy regulator on the injury of rat hippocampal neurons induced by oxygen-glucose deprivation (OGD). METHODS: Rat hippocampal neurons were cultivated in primary and subjected to OGD to simulate neuronal hypoxic ischemia injury for 2 hours or 6 hours followed by reperfusion for 12 hours with or without 3-methyladenine (3-MA, 20 µmol/L) or rapamycin (0.2 µmol/L). The morphology of neurons was observed with optical microscope. The expression of autophagy-related protein (LC3, P62) and apoptosis-related protein (cleaved caspase-3) were assessed by Western Blot analysis. The apoptosis of neurons was detected by flow cytometry, the release rate of lactate dehydrogenase (LDH) was calculated by automatic biochemical analyzer, and the cell activity was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. RESULTS: Compared with the control group, the expression of LC3 II/I (gray value: 3.091±0.160, 3.422±0.186 vs. 0.256±0.021), cleaved caspase-3 (gray value: 0.230±0.025, 0.440±0.051 vs. 0.050±0.007), neuronal apoptotic rate, LDH release rate [(38.50±4.15)%, (59.60±5.65)% vs. (12.40±1.32)%] were increased, while the expression of P62 (gray value: 0.290±0.025, 0.120±0.026 vs. 0.450±0.040), neuronal activity [(71.40±7.23)%, (42.80±4.12)% vs. (100.30±2.30)%] were decreased at 2 hours or 6 hours after OGD (all P < 0.05). When the time of OGD was 2 hours and it was combined with 3-MA, the expression of LC3 II/I (gray value: 2.281±0.121), the neuronal activity [(51.10±5.73)%] were decreased, while the expression of P62 and cleaved caspase-3 (gray scale: 0.410±0.037, 0.330±0.027, respectively), neuronal apoptotic rate, the injury of neurons [LDH release rate: (47.30±4.43)%] were increased (all P < 0.05). When the time of OGD was 2 hours and it was combined with rapamycin, the expression of LC3 II/I (gray value: 3.689±0.214), the neuronal activity [(85.30±8.56)%] were increased, while the expression of P62 and cleaved caspase-3 (gray value: 0.170±0.040, 0.090±0.096, respectively), neuronal apoptotic rate, the injury of neurons [LDH release rate: (24.30±2.14)%] were decreased (all P < 0.05). On the contrary, when the time of OGD was 6 hours and it was combined with 3-MA, the expression of LC3 II/I and cleaved caspase-3 (gray value: 3.021±0.178, 0.240±0.017), neuronal apoptotic rate, the injury of neurons [LDH release rate: (36.60±3.45)%] were decreased, while the expression of P62 (gray value: 0.350±0.060), the neuronal activity [(59.70±6.13)%] were increased (all P < 0.05). When the time of OGD was 6 hours and it was combined with rapamycin, the expression of LC3 II/I and cleaved caspase-3 (gray value: 3.923±0.201, 0.590±0.062), neuronal apoptotic rate, the injury of neurons [LDH release rate: (71.20±7.81)%] were increased, while the expression of P62 (gray value: 0.070±0.008), the neuronal activity [(27.30±2.12)%] were decreased (all P < 0.05). CONCLUSIONS: The enhancement of autophagy has protective effect on neurons under the condition of mild OGD, while it can aggravate the injury of neurons induced by a long-time OGD.

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