ABSTRACT
Introduction: Studies on the effect of vaccine type and two other vaccines other than inactivated vaccines approved in China on in vitro fertilization (IVF) pregnancy outcomes are rare. To complement and confirm the existing findings, this research aimed to investigate whether there are adverse effects of different vaccine types in females and males on reproductive function and clinical pregnancy. Methods: This retrospective study enrolled 6,455 fresh embryo transfer cycles at the First Affiliated Hospital of Zhengzhou University between May 1, 2021, and October 31, 2022. The primary outcome is the clinical pregnancy rate (CPR). At the same time, the secondary results are the number of oocytes retrieved, two pronuclei (2PN) rate, blastocyst formation rate, high-quality blastocyst rate, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DNA fragment index (DFI) rate). Results: In the comparison of ovarian stimulation indicators, no statistically significant differences (P > 0.05) were found in Gn days, endometrial thickness, 2PN rate, metaphase 2 (MII) rate, high-quality embryo rate, and blastocyst formation rate. No significant differences (P>0.05) were found in age, body mass index (BMI), education level, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DFI rate) in these four groups. The multivariate regression model showed that neither the types of vaccines nor the vaccination status of both infertile couples significantly affected clinical pregnancy. Discussion: The type of vaccine does not appear to have an unfavorable effect on ovarian stimulation, embryo development, semen parameters, and clinical pregnancy.
Subject(s)
COVID-19 Vaccines , COVID-19 , Pregnancy Outcome , Pregnancy Rate , Humans , Female , Pregnancy , Male , Retrospective Studies , Adult , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/epidemiology , Infertility , Fertilization in Vitro/methods , Vaccination/adverse effects , Ovulation Induction/methods , Reproduction/physiology , Embryo Transfer/methods , China/epidemiology , SARS-CoV-2ABSTRACT
Harvesting renewable mechanical energy is envisioned as a promising and sustainable way for power generation. Many recent mechanical energy harvesters are able to produce instantaneous (pulsed) electricity with a high peak voltage of over 100 V. However, directly storing such irregular high-voltage pulse electricity remains a great challenge. The use of extra power management components can boost storage efficiency but increase system complexity. Here utilizing the conducting polymer PEDOT:PSS, high-rate metal-free micro-supercapacitor (MSC) arrays are successfully fabricated for direct high-efficiency storage of high-voltage pulse electricity. Within an area of 2.4 × 3.4 cm2 on various paper substrates, large-scale MSC arrays (comprising up to 100 cells) can be printed to deliver a working voltage window of 160 V at an ultrahigh scan rate up to 30 V s-1. The ultrahigh rate capability enables the MSC arrays to quickly capture and efficiently store the high-voltage (≈150 V) pulse electricity produced by a droplet-based electricity generator at a high efficiency of 62%, significantly higher than that (<2%) of the batteries or capacitors demonstrated in the literature. Moreover, the compact and metal-free features make these MSC arrays excellent candidates for sustainable high-performance energy storage in self-charging power systems.
ABSTRACT
Basement membrane (BM) component deposition is closely linked to the establishment of cell polarity. Previously, we showed that Prickle1 is crucial for BM deposition and cell polarity events in tear duct elongation. To gain a deeper understanding of the intimate relationship between BM formation and cell polarity, we generated induced pluripotent stem cells (iPSCs)-derived embryoid bodies (EBs) with a basement membrane separating the visceral endoderm (VE) and inner EB cell mass. We found that Prickle1 was highly expressed in VE of the normal EBs, and the Prickle1 mutant EBs displayed severely impaired BM. Notably, the formation of the basement membrane appeared to rely on the proper microtubule network of the VE cells, which was disrupted in the Prickle1 mutant EBs. Moreover, disruption of vesicle trafficking in the VE hindered BM secretion. Furthermore, reintroducing Prickle1 in the mutant EBs completely rescued BM formation but not the apicobasal cell polarity of the VE. Our data, in conjunction with studies by others, highlight the conserved role of Prickle1 in directing the secretion of BM components of the VE cells during embryonic germ layer differentiation, even in the absence of established general polarity machinery. Our study introduces a novel system based on iPSCs-derived EBs for investigating cellular and molecular events associated with cell polarity.
Subject(s)
Basement Membrane , Cell Differentiation , Cell Polarity , Embryoid Bodies , Induced Pluripotent Stem Cells , LIM Domain Proteins , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Embryoid Bodies/metabolism , Embryoid Bodies/cytology , Basement Membrane/metabolism , LIM Domain Proteins/metabolism , LIM Domain Proteins/genetics , Animals , Mice , Endoderm/metabolism , Endoderm/cytology , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/geneticsABSTRACT
Genetic and environmental factors can independently or coordinatively drive ocular axis growth. Mutations in FRIZZLED5 (FZD5) have been associated with microphthalmia, coloboma, and, more recently, high myopia. The molecular mechanism of how Fzd5 participates in ocular growth remains unknown. In this study, we compiled a list of human genes associated with ocular growth abnormalities based on public databases and a literature search. We identified a set of ocular growth-related genes from the list that was altered in the Fzd5 mutant mice by RNAseq analysis at different time points. The Fzd5 regulation of this set of genes appeared to be impacted by age and light damage. Further bioinformatical analysis indicated that these genes are extracellular matrix (ECM)-related; and meanwhile an altered Wnt signaling was detected. Altogether, the data suggest that Fzd5 may regulate ocular growth through regulating ECM remodeling, hinting at a genetic-environmental interaction in gene regulation of ocular axis control.
Subject(s)
Frizzled Receptors , Microphthalmos , Animals , Humans , Mice , Frizzled Receptors/genetics , Frizzled Receptors/metabolism , Gene Expression Regulation , Wnt Signaling PathwayABSTRACT
STUDY QUESTION: Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER: Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY: When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION: A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS: As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.
Subject(s)
Abortion, Spontaneous , Natural Disasters , Pregnancy , Female , Humans , Male , Vitrification , Cryopreservation/methods , Retrospective Studies , Semen , Pregnancy Rate , Oocytes , Embryonic Development , Fertilization in VitroABSTRACT
BACKGROUND: This retrospective study aimed to investigate the most suitable endometrial thickness (EMT) on the day of embryo transfer that could reduce ectopic pregnancy rate (EPR) and improve clinical pregnancy rate (CPR) in fresh embryo transfer patients with early follicular phase long-acting regimen. METHODS: A total of 11,738 IVF/ICSI cycles, comprising 4,489 non-clinical pregnancies, 7,121 intrauterine pregnancies, and 128 ectopic pregnancy cycles after fresh embryo transfer, recorded between September 2017 and December 2020. Clinical pregnancy (CP) and ectopic pregnancy (EP) were the primary outcomes. Multivariate logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for EP and CP. Patients were divided into three groups based on the EMT (6-10 mm, 11-15 mm, and 16-20 mm). CPR and EPR per millimeter of EMT were drawn into a line chart, and three groups were analyzed by Chi-square test. RESULTS: After controlling for potential confounders, EMT had a significant effect on CP (aOR = 1.07; 95% CI, 1.05-1.08; P = 0.00) and EP (aOR = 0.88; 95% CI, 0.82-0.94; P = 0.00). With the increase of EMT, CPR increased and EPR decreased. Pearson correlation coefficients were r = 0.708 (P = 0.00) and r =-0.558 (P = 0.03), respectively. Significant differenceswere detected in the CPRs and EPRs (all P = 0.00). The CPR in the 6-10 mm group (54.88%) was significantly lower than that in the 11-15 mm group (64.23%) and the 16-20 mm group (64.40%) (P = 0.00). The EPR in the 6-10 mm group (2.72%) was significantly higher than that in the other two groups (1.60% and 0.97%, P = 0.00). The difference in CPR and EPR between the 11-15 mm group and the 16-20 mm group was not statistically significant, which indicated that EMT ≥ 11 mm simultaneously reduced the EPR and increased the CPR. CONCLUSIONS: EMT was inversely proportional to EPR and directly proportional to CPR in fresh embryo transfer cycles. The EMT ≥ 11 mm on the day of embryo transfer could simultaneously achieve lower EPR and higher CPR. Accordingly, more attention should be given to the EMT of women who underwent ART treatment.
Subject(s)
Endometrium , Pregnancy, Ectopic , Pregnancy , Humans , Female , Retrospective Studies , Pregnancy Rate , Endometrium/diagnostic imaging , Pregnancy, Ectopic/epidemiology , Embryo Transfer , Fertilization in VitroABSTRACT
Objectives: The aim of this study was to detect any gender bias in fetal malformation cases. Design: This study was a cross-sectional, quantitative survey. Subjects: Overall, 1,661 Asian fetal malformation cases involving induced abortions in the obstetrics department of the first Affiliated Hospital of Zhengzhou University from 2012 to 2021 were included. Main outcome measures: Measurements of ultrasound detectable structural malformations were classified into 13 subtypes. Karyotyping, single nucleotide polymorphism (SNP) array, or sequencing diagnosis of these fetus was also included in the outcome measures. Results: The sex ratio (male/female) of all malformation types was 1.446. Cardiopulmonary had the highest proportion of all malformation types with 28%. Diaphragmatic hernia, omphalocele, gastroschisis, nuchal translucency (NT), and Multy malformations had significantly higher proportions of males (p < 0.05). Digestive system malformations had a significantly higher proportion of females (p < 0.05). Maternal age was associated with genetic factors (r = 0.953, p < 0.001) and inversely associated with brain malformations (r = -0.570, p = 0.002). More males were found with trisomy 21, trisomy 18, and monogenetic diseases, while duplications, deletions, and uniparental disomy (UPD) had similar sex ratios between males and females, but not statistically significant. Conclusion: Sex differences are common with fetal malformations, with higher proportions of males. Genetic testing has been proposed to account for these differences.
Subject(s)
Down Syndrome , Sexism , Pregnancy , Humans , Female , Male , Cross-Sectional Studies , Down Syndrome/diagnosis , Karyotyping , Genetic TestingABSTRACT
Objective: To assess whether low-grade inflammation, measured by serum high-sensitivity C-reactive protein (hsCRP) levels, is associated with in vitro fertilization (IVF) outcomes. Design: A retrospective study. Setting: University-affiliated IVF center. Patients: In the present study, 875 women of normal weight who underwent their first fresh embryo transfer (ET) cycles for IVF treatment were divided into three groups according to serum concentrations of hsCRP. Interventions: Serum from women undergoing IVF was collected on days 2-4 of a spontaneous menstrual cycle prior to the commencement of ovarian stimulation. Main Outcome Measures: The IVF outcomes included implantation, biochemical pregnancy, clinical pregnancy, miscarriage and live birth rates. Results: The women were divided into three groups according to the baseline serum levels of hsCRP as follows: low hsCRP (<1 mg/L; n=517), medium hsCRP (1-3 mg/L; n= 270), high hsCRP (>3 mg/L; n=88). The maternal age was similar among the three groups. The women in the high and medium hsCRP group had significantly higher BMI compared with those in the low hsCRP group. The protocol of controlled ovarian hyperstimulation, the gonadotropin dose administered, the serum estradiol levels, progesterone levels and the endometrial thickness on the day of triggering, as well as the number of retrieved oocytes, fertilized oocytes and good quality embryos, and the oocyte maturation rate were similar among the three groups. Implantation, biochemical pregnancy and clinical miscarriage rates did not differ significantly were not significantly different among three groups. The clinical pregnancy rate was significantly lower in the high hsCRP group compared with that in the low hsCRP group (50.0% versus 63.4%; P<0.0167), which contributed to a significant decrease in birth rate (39.8% versus 53.8%; P<0.0167). High serum hsCRP levels was found to be a factor affecting live birth rate. Conclusions: Among women of normal weight undergoing their first IVF treatment, it was found that low-grade inflammation was associated with reduced clinical pregnancy and live birth rates following fresh ET cycles.
Subject(s)
C-Reactive Protein , Fertilization in Vitro , Pregnancy Rate , Female , Humans , Pregnancy , Abortion, Spontaneous/epidemiology , Inflammation , Retrospective StudiesABSTRACT
OBJECTIVE: This meta-analysis aimed to investigate the effects and safety of enhanced recovery after surgery (ERAS) for the management of pediatric colorectal surgery. METHODS: We retrieved relevant studies from PubMed, EMBASE, the Cochrane Library, and China National Knowledgement Infrastructure (CNKI) from its inception until 20 May 2022. Meta-analysis was performed using RevMan 5.4, and power analysis was calculated using G∗Power 3.1. RESULTS: Ten studies involving 1298 patients were included for meta-analysis. Meta-analysis suggested that ERAS protocol significantly lessened intraoperative fluids (mean difference [MD], -3.11; 95% confidence interval, -4.99 to -1.22) and postoperative opioid usage (MD, -0.58; 95% CI, -1.08 to -0.26), shortened time to bowel return (MD, -12.02; 95% CI, -20.03 to -4.02), first enteral nutrition (MD, -20.88; 95% CI, -28.34 to -13.42) and oral intake (MD, -1.40; 95% CI, -1.96 to -0.84), lowered readmission rate in 30 days (relative risk [RR], 0.61, 95% CI, 0.41 to 0.90), shortened length of hospital stay (MD, -1.50; 95% CI, -1.25 to -1.09), and reduced in-hospital costs (MD, -0.26; 95% CI, -0.34 to -0.18); however, there was a comparable rate of postoperative complications between the two groups. Sensitivity analysis significantly changed the result of the readmission rate in 30 days. The statistical power of all outcomes ranged from 26.84% to 99.44%. CONCLUSIONS: Our findings demonstrate the beneficial role of the ERAS protocol in accelerating rehabilitation, shortening the length of hospital stay, and decreasing in-hospital costs among pediatric patients undergoing colorectal surgery. LEVELS OF EVIDENCE: LEVEL V.
Subject(s)
Colorectal Surgery , Digestive System Surgical Procedures , Enhanced Recovery After Surgery , Child , Humans , China , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Clinical ProtocolsABSTRACT
OBJECTIVES: To explore the incidence of retained embryos (REs) in embryo transfer (ET) cycles and its effects on pregnancy outcomes in women undergoing in vitro fertilization (IVF). METHODS: This was a matched retrospective cohort study involving 29,160 ET cycles conducted from March 2016 to February 2021, in which ET cycles without RE were matched to the RE group at a 2:1 ratio. Clinical pregnancy, implantation, miscarriage, and live birth rates were compared between the with-RE and without-RE groups. RESULTS: Our study showed that the overall incidence of REs was 0.33% (95/29,160). There was a statistically significant difference in RE rate among the operators (P < 0.001), suggesting that the embryo retention rate may be affected by the individual operator. A total of 95 repeated ET cycles due to RE were included in the study group, and 190 ET cycles without RE were matched to the study group (1:2). There were no significant differences between the RE and matched groups in terms of implantation rate (35.6 vs. 38.0%; P = 0.608), clinical pregnancy rate (47.4 vs. 54.7%; P = 0.240), biochemical pregnancy rate (5.3 vs. 4.7%; P = 0.846), miscarriage rate (11.1 vs. 9.6%; P = 0.781), ectopic pregnancy rate (2.2 vs. 1.9%; P = 1.000) or live birth rate (41.1 vs. 48.9%; P = 0.208). CONCLUSIONS: The present findings demonstrated that immediate retransfer of REs did not significantly affect IVF outcomes, which may provide counselling information for patients when REs are identified and ET is reattempted. The incidence of REs was associated with the operator who expelled the embryos from the catheter. Attention to detail and frequent assessment of the operator's technique may facilitate avoidance of embryo retention.
Subject(s)
Abortion, Spontaneous , Pregnancy Outcome , Pregnancy , Humans , Female , Pregnancy Outcome/epidemiology , Abortion, Spontaneous/epidemiology , Retrospective Studies , Fertilization in Vitro/methods , Embryo Transfer/methods , Pregnancy Rate , Live Birth/epidemiologyABSTRACT
Major challenges in developing implanted neural stimulation devices are the invasiveness, complexity, and cost of the implantation procedure. Here, we report an injectable, nanofibrous 2D flexible hydrogel sheet-based neural stimulation device that can be non-invasively implanted via syringe injection for optoelectrical and biochemical dual stimulation of neuron. Specifically, methacrylated gelatin (GelMA)/alginate hydrogel nanofibers were mechanically reinforced with a poly(lactide-co-ε-caprolactone) (PLCL) core by coaxial electrospinning. The lubricant hydrogel shell enabled not only injectability, but also facile incorporation of functional nanomaterials and bioactives. The nanofibers loaded with photocatatlytic g-C3N4/GO nanoparticles were capable of stimulating neural cells via blue light, with a significant 36.3 % enhancement in neurite extension. Meanwhile, the nerve growth factor (NGF) loaded nanofibers supported a sustained release of NGF with well-maintained function to biochemically stimulate neural differentiation. We have demonstrated the capability of an injectable, hydrogel nanofibrous, neural stimulation system to support neural stimulation both optoelectrically and biochemically, which represents crucial early steps in a larger effort to create a minimally invasive system for neural stimulation.
Subject(s)
Nanofibers , Hydrogels/pharmacology , Nerve Growth Factor/pharmacology , Neurons , Prostheses and ImplantsABSTRACT
Peripheral nerve regeneration with large defects needs innovative design of nerve guidance conduits (NGCs) which possess anisotropic guidance, electrical induction and right mechanical properties in one. Herein, we present, for the first time, facile fabrication and efficient neural differentiation guidance of anisotropic, conductive, self-snapping, hydrogel-based NGCs. The hydrogels were fabricated via crosslinking of graphitic carbon nitride (g-C3N4) upon exposure with blue light, incorporated with graphene oxide (GO). Incorporation of GO and in situ reduction greatly enhanced surface charges, while decayed light penetration endowed the hydrogel with an intriguing self-snapping feature by the virtue of a crosslinking gradient. The hydrogels were in the optimal mechanical stiffness range for peripheral nerve regeneration and supported normal viability and proliferation of neural cells. The PC12 âcells differentiated on the electroactive g-C3N4 H/rGO3 (3 âmg/mL GO loading) hydrogel presented 47% longer neurite length than that of the pristine g-C3N4 H hydrogel. Furthermore, the NGC with aligned microchannels was successfully fabricated using sacrificial melt electrowriting (MEW) moulding, the anisotropic microchannels of the 10 âµm width showed optimal neurite guidance. Such anisotropic, electroactive, self-snapping NGCs may possess great potential for repairing peripheral nerve injuries.
ABSTRACT
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.
Subject(s)
Azoospermia , MicroRNAs , 3' Untranslated Regions , Autophagy/genetics , Autophagy-Related Protein 7/genetics , Azoospermia/genetics , Beclin-1/genetics , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Objective: To investigate the effect of BMI in male and/or female partners on embryo development and clinical pregnancy outcome during ART. Methods: Data of 11,130 cycles between January 2018 and December 2020 were retrospectively analyzed. They were divided into Group A, B, C, and D based on couples' BMI values, also were divided into Group I, II, III and IV in IVF cycles and Group i, ii, iii, and iv in ICSI cycles. After grouping, inter-group indicators comparisons and logistic regression analysis were performed. Results: In IVF cycles, CPR in Group I and Group III were higher than Group IV. In Group III, it was higher than Group II. The AR in Group IV was higher, but the LBR was lower than Group I, Group II, and Group III. Logistic regression analysis results suggested that AR in Group IV was higher than that in Group I in IVF cycles, whereas LBR was lower.In ICSI cycles, high-quality embryo rate in Group i and Group ii were both higher than that in Group iii and Group iv. The CPR in Group i was higher than Group ii and Group iv, and in Group iii was higher than Group ii and Group iv. The AR in Group i was lower than Group iii and Group iv, and AR in Group ii was lower than Group iv. LBR, in Group I it was higher than Group ii, Group iii, and Group iv. Logistic regression analysis results suggested CPR in Group ii was significantly lower than that in Group i. AR in Group iii was considerably higher than that in Group i. LBR in Group ii and Group iv were significantly lower than that in Group i. Conclusion: Female higher BMI was not conducive to the formation of high-quality embryos in ICSI cycle. Female and/or male BMI affected AR and LBR more than CPR not only in IVF cycles, but also in ICSI cycles.
Subject(s)
Pregnancy Outcome , Sperm Injections, Intracytoplasmic , Body Mass Index , Embryonic Development , Female , Fertilization in Vitro/methods , Humans , Male , Pregnancy , Pregnancy Outcome/epidemiology , Retrospective Studies , Sperm Injections, Intracytoplasmic/methodsABSTRACT
Ever-growing various applications, especially for tissue regeneration, cause a pressing need for novel methods to functionalize melt electrowritten (MEW) microfibrous scaffolds with unique nanomaterials. Here, two novel strategies are proposed to modify MEW polycaprolactone (PCL) grids with ZnO nanoparticles (ZP) or ZnO nanoflakes (ZF) to enhance osteogenic differentiation. The calcium mineralization levels of MC3T3 osteoblasts cultured on PCL/ZP 0.1 scaffolds are â¼3.91-fold higher than those cultured on nonmodified PCL scaffolds, respectively. Due to the nanotopography mimicking bone anatomy, the PCL/ZF scaffolds (â¼2.60 times higher in ALP activity compared to PCL/ZP 1 and â¼2.17 times higher in mineralization compared to PCL/ZP 0.1) achieved superior results. Moreover, the flexible feature inherited from PCL grids makes it possible for them to act as a reshapable osteogenic bioscaffold. This study provides new strategies for synthesizing nanomaterials on microscale surfaces, opening up a new route for functionalizing MEW scaffolds to fulfill the growing demand of tissue engineering.
Subject(s)
Biocompatible Materials , Zinc Oxide , Cell Differentiation , Osteogenesis , Polyesters , Tissue Engineering/methods , Tissue ScaffoldsABSTRACT
Photoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as nonsyndromic retinal degenerations. Despite extensive studies, many questions remain in the mechanism of protein trafficking across the photoreceptor CC. Here, we genetically inactivated mouse Tmem138, a gene encoding a putative transmembrane protein localized to the ciliary TZ and linked to ciliopathies. Germline deletion of Tmem138 abolished OS morphogenesis, followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and was required for localization of Ahi1 to the distal subdomain of the CC. Among the examined set of OS proteins, rhodopsin was mislocalized throughout the mutant cell body prior to OS morphogenesis. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing failure of disc renewal and disintegration of the OS. Furthermore, Tmem138 interacts reciprocally with rhodopsin and a related protein Tmem231, and the ciliary localization of the latter was also altered in the mutant photoreceptors. Taken together, these results suggest a crucial role of Tmem138 in the functional organization of the CC, which is essential for rhodopsin localization and OS biogenesis.
Subject(s)
Ciliopathies , Retinal Degeneration , Cilia/metabolism , Ciliopathies/metabolism , Humans , Membrane Proteins , Photoreceptor Connecting Cilium , Retinal Degeneration/metabolism , Rhodopsin/genetics , Rhodopsin/metabolismABSTRACT
Parkinson's disease (PD) is a usual disease caused by degeneration of the central nervous system, which features the denaturation and death of dopaminergic neurons in the substantia nigra compact (SNc) of the midbrain. Neuroinflammation casts a consequential role in its pathogenesis, and the excessive activation of microglia as a major part of neuroinflammation cannot be ignored. Studies have indicated that Hordenine (HOR) functioned widely as an anti-oxidant and anti-inflammatory substance, but there are no reports on neuroinflammation effects. Therefore, this study is devoted to exploring the effect of HOR on neuroinflammation and its specific mechanism. In vivo, results revealed that HOR depressed the activation of microglia in SNc and protected dopaminergic neurons in the 6-hydroxydopamine (6-OHDA)-induced PD rat model, which terminally reduced movement disorders and weight loss. In vitro, studies have shown that HOR can inhibit inflammatory responses triggered by lipopolysaccharide (LPS) in BV-2 cells. More profound studies have discovered that the specific anti-inflammatory mechanism is intimately associated with the NF-κB and MAPK signaling pathways. All in it together, HOR acts as a significant role in preserving dopaminergic neurons by restraining neuroinflammation mediated by activation of microglia. This may provide a potential drug for Parkinson's treatment.
Subject(s)
Neuroprotective Agents , Parkinson Disease , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cell Line , Lipopolysaccharides/pharmacology , MAP Kinase Signaling System , Microglia , NF-kappa B/metabolism , Neuroinflammatory Diseases , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Parkinson Disease/drug therapy , Rats , Tyramine/analogs & derivativesABSTRACT
Water uptake facilitates the initiation of seed germination. It is presumed that aquaporin (AQP)-mediated water inflow contributes to seed germination, but the genetic evidence is still lacking. This study aimed at genome-wide identification of ZmAQPs and further determined the physiological functions. Following a comprehensive search, a total of 41 ZmAQPs were identified according to the latest genome database. Through bioinformatic approaches, the physicochemical characteristics, phylogenetic relationships, and structural features of ZmAQPs were analyzed. The gene expression analysis of 20 high-resolution and multi-tissues samples showed that ZmAQPs had distinct spatiotemporal and tissue-specific expression profiles during seed germination and early seedling development. We then focused on the aquaporin of maize tonoplast intrinsic protein 3 (ZmTIP3), which is specifically expressed in germinating seed. A mutant zmtip3-1 with disruption of the ZmTIP3-1 gene showed shorter shoot and root length, and decreased seedling dry weight compared with the control (W22). The result revealed that ZmTIP3-1 improved the absolute content of seed protein and promoted storage reserves mobilization, suggesting that ZmTIP3 may be a positive regulator of seed vigor. This work provides valuable clues for understanding the function and possible regulatory mechanism of ZmAQPs in seed germination and seedling growth.
ABSTRACT
Nanocomposite percolation networks have attracted increasing attention in the field of wearable devices. Generally, the large junction resistance caused by the small contact area in the percolation network is considered as the bottleneck in preparing high-performance electronics. In such electronics, an applied strain will lead to deformation on the fiber junction, subsequently increasing the sheet resistance. However, taking advantage of the dominant role of the contact resistance in the percolation network, the overall resistance of the network can be controlled by skillfully adjusting the contact area. Here, we designed a combined gold-polycaprolactone (Au-PCL) network with a unique buckling net structure. When the thickness of the gold nanolayer is 50 nm, the network shows typical percolation behavior with high transparency (93%), good conductivity (20 Ω/sq), and good ductility. Moreover, the networks show a unique positive relationship between the conductivity and strain due to the variation of contact resistance. By designing different waving angles, the network can be used as a dynamic strain sensor with a tunable gauge factor ranging from -0.8 to -1.8. Overall, these highly stretchable and transparent Au-PCL networks show promising applications in the field of high-performance electronic and optoelectronic nanodevices.
ABSTRACT
Mastitis causes great psychological and physical pain among women. Our previous studies found that niacin has anti-inflammatory effect, and the realization of this function depends on GPR109A. However, there are no previous reports about the anti-inflammatory function of GPR109A in mastitis. In our study, we observed the effect of niacin on the WT and GPR109A-/- mice mastitis model. The results showed that administration of niacin to WT mice reduced the damage, proinflammatory mediators and protected the integrity of the blood milk barrier in mammary gland. While in GPR109A-/- mice, there was no effect on the above indexes. In mammary epithelial cells, GPR109A was able to promote autophagy and Nrf2 nuclear import through AMPK. In LPS-induced mammary epithelial cells, niacin inhibited the LPS-induced inflammatory response and downregulation of tight junction proteins, and these effects were eliminated by knocking down GPR109A, blocking autophagy or inhibiting Nrf2 nuclear import. These results indicate that in mastitis, GPR109A promotes autophagy and Nrf2 nuclear import through AMPK, thereby inhibiting inflammatory damage to the mammary gland and repairing the blood milk barrier. Our results suggested that GPR109A may be a potential target for the treatment of mastitis.