Tetramethylpyrazine alleviates hypoxia-induced proliferation, migration, and inflammatory response of fibroblast-like synoviocytes via inhibiting the HIF-1α- circCDC42BPB pathway.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which might trigger cartilage, bone damage, and disability. Recent studies have suggested that Tetramethylpyrazine (TMP), an alkaloid monomer isolated from the rhizome of the traditional herbal medicine Ligusticum wallichii Franch, exerts a broad spectrum of pharmacological properties, containing anti-inflammatory. This study aimed to analyze the role and underlying mechanism of TMP in RA. METHODS: Under Hypoxia condition, RA-Fibroblast-like synoviocyte (FLS) were treated with TMP at different doses. Cell viability, proliferation, cell cycle progression, and migration were detected using Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry assay, wound healing assay, and transwell assay. Cyclin D1, Proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase-2 (MMP2), MMP9, and hypoxia-inducible factor-1α (HIF-1α) protein levels were measured using western blot assay. Interleukin-6 (IL-6) and IL-8 were evaluated using ELISA. Circular RNA (circRNA) hsa_circ_0005178 (circCDC42BPB), CDC42BPB, and HIF-1α expression were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Binding between HIF-1α and CDC42BPB promoter was predicted by JASPAR and verified using dual-luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. RESULTS: TMP might hinder FLS proliferation, cycle progression, migration, and inflammatory response under hypoxic conditions. CircCDC42BPB expression was increased in RA patients and RA-FLSs treated with hypoxia, while its level was obviously reduced in RA-FLSs treated with hypoxia and TMP. TMP might abolish hypoxia-induced circCDC42BPB expression. Upregulation of circCDC42BPB might partially overturn the repression of TMP on hypoxia-caused RA-FLS damage. TMP might regulate circCDC42BPB level via HIF-1α in RA-FLSs under hypoxic conditions. CONCLUSION: TMP might block RA-FLS injury partly via regulating the HIF-1α- circCDC42BPB pathway, providing a promising therapeutic target for RA.

HIGHLIGHTS: • TMP suppressed hypoxia-induced RA-FLS growth and inflammatory response.• TMP might repress circCDC42BPB expression in RA-FLSs under hypoxic conditions.• TMP might inhibit HIF-1α-induced circCDC42BPB transcription under hypoxic conditions.

Super-Stretchable and High-Energy Micro-Pseudocapacitors Based on MXene Embedded Ag Nanoparticles.

The advancement of aqueous micro-supercapacitors offers an enticing prospect for a broad spectrum of applications, spanning from wearable electronics to micro-robotics and sensors. Unfortunately, conventional micro-supercapacitors are characterized by low capacity and slopy voltage profiles, limiting their energy density capabilities. To enhance the performance of these devices, the use of 2D MXene-based compounds has recently been proposed. Apart from their capacitive contributions, these structures can be loaded with redox-active nanowires which increase their energy density and stabilize their operation voltage. However, introducing rigid nanowires into MXene films typically leads to a significant decline in their mechanical properties, particularly in terms of flexibility. To overcome this issue, super stretchable micro-pseudocapacitor electrodes composed of MXene nanosheets and in situ reconstructed Ag nanoparticles (Ag-NP-MXene) are herein demonstrated, delivering high energy density, stable operation voltage of ≈1 V, and fast charging capabilities. Careful experimental analysis and theoretical simulations of the charging mechanism of the Ag-NP-MXene electrodes reveal a dual nature charge storage mechanism involving ad(de)sorption of ions and conversion reaction of Ag nanoparticles. The superior mechanical properties of synthesized films obtained through in situ construction of Ag-NP-MXene structure show an ultra stretchability, allowing the devices to provide stable voltage and energy output even at 100% elongation.

Respiratory syncytial virus co-opts hypoxia-inducible factor-1α-mediated glycolysis to favor the production of infectious virus.

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading etiological agent of lower respiratory tract illness. However, efficacious vaccines or antiviral drugs for treating RSV infections are currently not available. Indeed, RSV depends on host cells to provide energy needed to produce progeny virions. Glycolysis is a series of oxidative reactions used to metabolize glucose and provide energy to host cells. Therefore, glycolysis may be helpful for RSV infection. In this study, we show that RSV increases glycolysis by inducing the stabilization, transcription, translation, and activation of hypoxia-inducible factor (HIF)-1α in infected cells, which is important for the production of progeny RSV virions. This study contributes to understanding the molecular mechanism by which HIF-1α-mediated glycolysis controls RSV infection and reveals an effective target for the development of highly efficient anti-RSV drugs.

Three-Dimensional Zinc-Seeded Carbon Nanofiber Architectures as Lightweight and Flexible Hosts for a Highly Reversible Zinc Metal Anode.

Uneven zinc (Zn) deposition typically leads to uncontrollable dendrite growth, which renders an unsatisfactory cycling stability and Coulombic efficiency (CE) of aqueous zinc ion batteries (ZIBs), restricting their practical application. In this work, a lightweight and flexible three-dimensional (3D) carbon nanofiber architecture with uniform Zn seeds (CNF-Zn) is prepared from bacterial cellulose (BC), a kind of biomass with low cost, environmental friendliness, and abundance, as a host for highly reversible Zn plating/stripping and construction of high-performance aqueous ZIBs. The as-prepared 3D CNF-Zn with a porous interconnected network significantly decreases the local current density, and the functional Zn seeds provide uniform nuclei to guide the uniform Zn deposition. Benefiting from the synergistic effect of Zn seeds and the 3D porous framework in the flexible CNF-Zn host, the electrochemical performance of the as-constructed ZIBs is significantly improved. This flexible 3D CNF-Zn host delivers a high and stable CE of 99.5% over 450 cycles, ensuring outstanding rate performance and a long cycle life of over 500 cycles at 4 A g-1 in the CNF-Zn@Zn//NaV3O8·1.5H2O full battery. More importantly, owing to the flexibility of the 3D CNF-Zn host, the as-assembled pouch cell shows outstanding mechanical flexibility and excellent energy storage performance. This strategy of producing readily accessible carbon from biomass can be employed to develop advanced functional nanomaterials for next-generation flexible energy storage devices.

Combinatorial Metabolic Engineering of Escherichia coli for Enhanced L-Cysteine Production: Insights into Crucial Regulatory Modes and Optimization of Carbon-Sulfur Metabolism and Cofactor Availability.

Microbial production of valuable compounds can be enhanced by various metabolic strategies. This study proposed combinatorial metabolic engineering to develop an effective Escherichia coli cell factory dedicated to L-cysteine production. First, the crucial regulatory modes that control L-cysteine levels were investigated to guide metabolic modifications. A two-stage fermentation was achieved by employing multi-copy gene expression, improving the balance between production and growth. Subsequently, carbon flux distribution was further optimized by modifying the C1 unit metabolism and the glycolytic pathway. The modifications of sulfur assimilation demonstrated superior performance of thiosulfate utilization pathways in enhancing L-cysteine titer. Furthermore, the studies focusing on cofactor availability and preference emphasized the vital role of synergistic enhancement of sulfur-carbon metabolism in L-cysteine overproduction. In a 5 L bioreactor, the strain BW15-3/pED accumulated 12.6 g/L of L-cysteine. This work presented an effective metabolic engineering strategy for the development of L-cysteine-producing strains.

Molecular cytogenetic characterization of de novo concomitant proximal 21q deletion of 21q11.2q21.3 and distal Xp deletion of Xp22.33p22.2 due to an unbalanced X;21 translocation detected by amniocentesis.

OBJECTIVE: We present molecular cytogenetic characterization of de novo concomitant proximal 21q deletion of 21q11.2q21.3 and distal Xp deletion of Xp22.33p22.2 due to an unbalanced X; 21 translocation detected by amniocentesis. CASE REPORT: A 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X,der(X)t(X; 21) (p22.2; q21.3),-21. Simultaneous array comparative genomic hybridization (aCGH) revealed the result of an 11.9-Mb Xp22.33p22.2 deletion encompassing HCCS, SHOX, AMELX and OFD1 and a 15.4-Mb 21q11.2q21.3 deletion encompassing NRIP1 and APP. The pregnancy was subsequently terminated, and a malformed fetus was delivered with craniofacial dysmorphism. The parental karyotypes were normal. Polymorphic DNA marker analysis by quantitative fluorescence polymerase chain reaction (QF-PCR) confirmed a paternal origin of the 21q proximal deletion. Cytogenetic analysis of cord blood confirmed the karyotype of 45,X,der(X)t(X; 21) (p22.2; q21.3),-21. aCGH analysis of the cord blood confirmed the prenatal diagnosis. CONCLUSION: QF-PCR analysis is useful for determination of the parental origin of a de novo unbalanced X; autosome translocation detected by prenatal diagnosis. The information acquired is useful for genetic counseling under such a circumstance.

Mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line.

OBJECTIVE: We present mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line. CASE REPORT: A 33-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety, and the karyotype of cultured amniocytes was 47,XX,+21[4]/46,XX[13]. In 17 colonies of cultured amniocytes, four colonies had 47,XX,+21, while the other 13 colonies had 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.32] consistent with 32% mosaicism for trisomy 21. Repeat amniocentesis performed at 25 weeks of gestation revealed 47,XX,+21[4]/46,XX[24] with four colonies of 47,XX,+21 and 24 colonies of 46, XX on cultured amniocytes, and arr 21q11.2q22.3 × 2.25 by aCGH, 19.2% mosaicism for trisomy 21 (20/104 cells) by interphase fluorescence in situ hybridization (FISH), and no uniparental disomy (UPD) 21 by quantitative fluorescence polymerase chain reaction (QF-PCR) on uncultured amniocytes. The parental karyotypes were normal, and prenatal ultrasound was unremarkable. A phenotypically normal 2815-g female baby was delivered at 38 weeks of gestation. Cytogenetic analysis on the cord blood, umbilical cord and placenta revealed the karyotype of 47,XX,+21[10]/46,XX[30]. 47,XX,+21[5]/46,XX[35] and 47,XX,+21[38]/46,XX[2], respectively. QF-PCR analysis on the DNA extracted from parental bloods, uncultured amniocytes, cord blood, umbilical cord and placenta confirmed a paternal origin of trisomy 21. When follow-up at age two months, the neonate was phenotypically normal, the peripheral blood had a karyotype of 47,XX,+21[6]/46,XX[34], and no trisomy 21 signals by interphase FISH was found on 100 buccal mucosal cells. When follow-up at age 13 months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+21[3]/46,XX[37]. CONCLUSION: Mosaic trisomy 21 at amniocentesis can be a transient and benign condition, and the abnormal trisomy 21 cell line may decrease and disappear after birth.

Prenatal diagnosis and molecular cytogenetic characterization of a de novo deletion of 4q34.1→qter associated with low PAPP-A and low PlGF in the first-trimester maternal serum screening, congenital heart defect on fetal ultrasound and a false negative non-invasive prenatal testing (NIPT) result.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo deletion of 4q34.1→qter associated with low pregnancy associated plasma protein-A (PAPP-A) and low placental growth factor (PlGF) in the first-trimester maternal serum screening, congenital heart defect (CHD) on fetal ultrasound and a false negative non-invasive prenatal testing (NIPT) result. CASE REPORT: A 40-year-old, primigravid woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). First-trimester maternal serum screening at 12 weeks of gestation revealed low PAPP-A [0.349 multiples of the median (MoM)] and low PlGF (0.299 MoM) and showed a risk for fetal trisomy 21 and trisomy 13. However, NIPT detected no genomic imbalance and a normal result. Nevertheless, level II ultrasound revealed ventricular septal defect, single umbilical artery and a small brain midline cyst. Amniocentesis revealed a karyotype of 46,XX,del(4)(q34.1) and a 17.8-Mb deletion of 4q34.1q.35.2 on array comparative genomic hybridization (aCGH) analysis. The parental karyotypes were normal. The pregnancy was terminated at 23 weeks of gestation, and a malformed fetus was delivered with craniofacial dysmorphism. Postnatal cytogenetic analysis of the placenta confirmed the prenatal diagnosis. There was a 17.8-Mb deletion of 4q34.1q.35.2 encompassing the genes of HAND2, SORBS2 and DUX4. Polymorphic DNA marker analysis on the parental bloods and cord blood showed a paternal origin of the deletion. CONCLUSION: An abnormal first-trimester maternal serum screening result along with abnormal fetal ultrasound should alert the possibility of fetal aneuploidy, and amniocentesis is indicated even in the presence of a normal NIPT result.

PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K.

Phosphoinositide-3 kinase (PI3K) signaling regulates many cellular processes, including cell survival, differentiation, proliferation, cytoskeleton reorganization, and apoptosis. The actin cytoskeleton regulated by PI3K signaling plays an important role in plasma membrane rearrangement. Currently, it is known that respiratory syncytial virus (RSV) infection requires PI3K signaling. However, the regulatory pattern or corresponding molecular mechanism of PI3K signaling on cell-to-cell fusion during syncytium formation remains unclear. This study synthesized a novel PI3K inhibitor PIK-24 designed with PI3K as a target and used it as a molecular probe to investigate the involvement of PI3K signaling in syncytium formation during RSV infection. The results of the antiviral mechanism revealed that syncytium formation required PI3K signaling to activate RHO family GTPases Cdc42, to upregulate the inactive form of cofilin, and to increase the amount of F-actin in cells, thereby causing actin cytoskeleton reorganization and membrane fusion between adjacent cells. PIK-24 treatment significantly abolished the generation of these events by blocking the activation of PI3K signaling. Moreover, PIK-24 had an obvious binding activity with the p85α regulatory subunit of PI3K. The anti-RSV effect similar to PIK-24 was obtained after knockdown of p85α in vitro or knockout of p85α in vivo, suggesting that PIK-24 inhibited RSV infection by targeting PI3K p85α. Most importantly, PIK-24 exerted a potent anti-RSV activity, and its antiviral effect was stronger than that of the classic PI3K inhibitor LY294002, PI-103, and broad-spectrum antiviral drug ribavirin. Thus, PIK-24 has the potential to be developed into a novel anti-RSV agent targeting cellular PI3K signaling. IMPORTANCE PI3K protein has many functions and regulates various cellular processes. As an important regulatory subunit of PI3K, p85α can regulate the activity of PI3K signaling. Therefore, it serves as the key target for virus infection. Indeed, p85α-regulated PI3K signaling facilitates various intracellular plasma membrane rearrangement events by modulating the actin cytoskeleton, which may be critical for RSV-induced syncytium formation. In this study, we show that a novel PI3K inhibitor inhibits RSV-induced PI3K signaling activation and actin cytoskeleton reorganization by targeting the p85α protein, thereby inhibiting syncytium formation and exerting a potent antiviral effect. Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens, causing enormous morbidity, mortality, and economic burden. Currently, no effective antiviral drugs or vaccines exist for RSV infection. This study contributes to understanding the molecular mechanism by which PI3K signaling regulates syncytium formation and provides a leading compound for anti-RSV infection drug development.

Mosaic trisomy 18 at amniocentesis associated with a favorable fetal outcome in a pregnancy.

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 18 by amniocentesis associated with a favorable fetal outcome in a pregnancy. CASE REPORT: A 42-year-old, gravida 4, para 2, woman underwent amniocentesis at 18 weeks of gestation because advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+18[6]/46,XX[17]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes showed the result of 45% mosaicism for trisomy 18. At 25 weeks of gestation, the woman underwent repeat amniocentesis which revealed a karyotype of 47,XX,+18[10]/46,XX[24]. Simultaneous aCGH on uncultured amniocytes showed the result of arr 18p11.32q23 (148,963-78,012,829) × 2.3 [GRCh (hg19)] with a log2 ratio of 0.2-0.25 compatible with 30-38% mosaicism for trisomy 18. The parental karyotypes were normal. Prenatal ultrasound was unremarkable. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes showed 27% (27/100 cells) mosaicism for trisomy 18. Quantitative fluorescent polymerase chain reaction (QF-PCR) on uncultured amniocytes excluded uniparental disomy (UPD) 18. Non-invasive prenatal testing (NIPT) analysis at 34 weeks of gestation revealed a significant gene dosage increase of chromosome 18 (29.95; normal control: -3.0-3.0). At 39 weeks of gestation, a 2840-g phenotypically normal baby was delivered. The cord blood had a karyotype of 47,XX,+18[8]/46,XX[32]. The placenta was trisomy 18 of maternal origin. The umbilical cord had a karyotype of 47,XX,+18[2]/46,XX[38]. At age 1½ months, the peripheral blood had a karyotype of 47,XX,+18[5]/46,XX[35], and FISH analysis on buccal mucosal cells revealed 2% (2/102 cells) mosaicism for trisomy 18. When follow-up at age seven months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+18[1]/46,XX[39]. CONCLUSIONS: Mosaic trisomy 18 at amniocentesis without abnormal fetal ultrasound can be associated with a favorable outcome, and the abnormal trisomy 18 cell line may decrease progressively after birth.

High-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line.

OBJECTIVE: We present prenatal diagnosis of high-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line. CASE REPORT: A 36-year-old, gravida 4, para 3, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[22]/46,X,idic(Y)(q11.2)[4]. Prenatal ultrasound was unremarkable, and the fetus had normal male external genitalia. Repeat amniocentesis was performed at 20 weeks of gestation, and the second amniocentesis revealed a karyotype of 45,X[24]/46,X,idic(Y)(q11.2)[3]. Simultaneous interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed that 60% (62/103 cells) were Y-deleted cells. After genetic counseling, the parents decided to continue the pregnancy, and a 3020-g male baby was delivered with a body length of 52 cm, normal male genital organs and no phenotypic abnormalities. The karyotypes of cord blood, umbilical cord and placenta were 45,X[20]/46,X,idic(Y)(q11.2)[20], 45,X[31]/46,X,idic(Y)(q11.2)[9] and 45,X[40], respectively. At age one month, FISH analysis on urinary cells and buccal mucosal cells revealed 11.5% (7/61 cells) and 13.6% (16/118 cells), respectively for mosaicism for the Y-deleted cells. At age five month, the karyotype of peripheral blood was 45,X[9]/46,X,idic(Y)(q11.2)[31]. FISH analysis on buccal mucosal cells showed no abnormal Y-deleted cell (0/101 cells). At age 11 month, the karyotype of peripheral blood was 45,X[5]/46,X,idic(Y)(q11.2)[35]. FISH analysis on 102 buccal mucosal cells showed no abnormal signals. The infant was doing well with normal physical and psychomotor development. CONCLUSION: High-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis can be associated with a favorable outcome and progressive decrease of the 45,X cell line.

Perinatal cytogenetic discrepancy in a pregnancy with mosaic 45,X/46, XY at amniocentesis and a favorable outcome.

OBJECTIVE: We present perinatal cytogenetic discrepancy in a pregnancy with mosaic 45,X/46, XY at amniocentesis and a favorable outcome. CASE REPORT: A 38-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[2]/46,XY[6]. Level II ultrasound at 20 weeks of gestation was unremarkable, and the fetus had normal male external genitalia. Following genetic counseling, the woman decided to continue the pregnancy. At 39 weeks of gestation, a healthy male baby was delivered with a body weight of 3410 g and a body length of 54.5 cm. The male external genital organs were normal. The cord blood had a karyotype of 46, XY (40/40 cells). The umbilical cord had a karyotype of 45,X[1]/46,XY[39]. During follow-up at age one month, his body weight was 4.4 Kg (15th-50th centile), and his body length was 56 cm (50th-85th centile). The infant was doing well. Interphase fluorescence in situ hybridization analysis on 100 buccal mucosal cells revealed no abnormal Y-deletion cell, and all cells contained one Y signal. CONCLUSION: Perinatal cytogenetic discrepancy may occur in the pregnancy with mosaic 45,X/46, XY at amniocentesis.

Prenatal diagnosis and molecular cytogenetic characterization of mosaic ring chromosome 21 associated with low PAPP-A and low PlGF in the first-trimester maternal serum screening.

OBJECTIVE: We present diagnosis and molecular cytogenetic characterization of mosaic ring chromosome 21 [r(21)]. CASE REPORT: A 17-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of an abnormal result of the first-trimester maternal serum screening for Down syndrome with a free ß-hCG level of 1.736 multiples of the median (MoM), a pregnancy associated plasma protein-A (PAPP-A) level of 0.275 MoM, a placental growth factor (PlGF) level of 0.281 MoM, a Down syndrome risk of 1:222 and a preeclampsia risk of 1:175. Cytogenetic analysis of cultured amniocytes revealed the result of 46,XX,r(21) (p12q22.3)[19]/45,XX,-21[13]. Array comparative genomic hybridization (aCGH) analysis of cultured amniocytes revealed the result of arr [GRCh37] 21q11.2q22.2 (15,485,008-40,625,594) × 1∼2, 21q22.2q22.3 (40,703,792-46,682,184) × 2∼3, 21q22.3 (46,761,631-48,084,156) × 1, consistent with mosaic monosomy 21 and r(21) (p12q22.3). The pregnancy was subsequently terminated, and a malformed fetus was delivered with low-set ears and hypotelorism. Postnatal cytogenetic analysis revealed a karyotype of 46,XX,r(21) (p12q22.3)[30]/45,XX,-21[8]/46,XX,idic r(21) (p12q22.3)[2] in the cord blood, 46,XX,r(21) (p12q22.3)[34]/45,XX,-21[6] in the skin, 46,XX,r(21) (p12q22.3)[37]/45,XX,-21[3] in the umbilical cord and 46,XX,dup(21) (q22.2q22.3)[32]/46,XX,r(21) (p12q22.3)[8] in the placenta. aCGH analysis of cord blood revealed the result of arr 21q11.2q22.2 (15,499,847-40,662,581) × 2.3, arr 21q22.2q22.3 (40,703,792-46,682,184) × 3.6, arr 21q22.3 (46,761,632-48,090,317) × 1, consistent with mosaic duplication of 21q11.2-q22.2 and 21q22.2-q22.3, and a 1.33-Mb 21q22.3 deletion encompassing the genes of COL18A1, SLC19A1, PCBP3, COL6A1, COL6A2, FTCD, LSS, MCM3AP, YBEY, PCNT, DIP2A, S100B and PRMT2. CONCLUSION: Mosaic r(21) at amniocentesis may be associated with monosomy 21, idic r(21) and dup(21), and low PAPP-A and low PlGF in the first-trimester maternal serum screening.

Altered DNA Methylation and Gene Expression Profiles in Radiation-Induced Heart Fibrosis of Sprague-Dawley Rats.

Radiation-induced heart disease (RIHD) is a serious side effect of radiotherapy for thoracic tumors. Advanced myocardial fibrosis in the late phase of RIHD can lead to myocardial remodeling, heart function impairing and heart failure, resulting in serious clinical consequences, and its pathogenesis remains vague. DNA methylation is one of the important epigenetic mechanisms which often occurs in response to environmental stimuli and is crucial in regulating gene expression. We hypothesized DNA methylation may contribute to pathogenesis in radiation-induced heart fibrosis (RIHF) and altered DNA methylation patterns probably influenced the genes expression in RIHF. In present study, we found genome-wide differences in DNA methylation status and RNA expression were demonstrated and we screened out 44 genes whose altered expression maybe were regulated by CpG island methylation within the gene promoter in RIHF of Sprague-Dawley rat by employing gene expression arrays and human CpG island microarrays. Gene expression and CpG island methylation levels of several candidate genes were further validated. Our investigation provided a new dimension to reveal the specific mechanisms of RIHF and explore the potential therapeutic targets for it.

Biomimetic Design of Macroporous 3D Truss Materials for Efficient Interfacial Solar Steam Generation.

Interfacial solar steam generation (ISSG) utilizing local heating technology for evaporation at the water-to-steam interface is drawing great attention because of its high efficiency of solar-thermal conversion for a sustainable and eco-friendly drinking water regeneration process. Here, inspired by the structure of penguin feathers and polar bear hairs that both have macropores to trap air for thermal insulation, we report a bionic solar evaporator (BSE) with macroporous skeleton for partial thermal management and macro patulous channels for abundant water transportation and rapid steam extraction. Meanwhile, the 3D hierarchical isotropic truss structures can induce multiple light reflections to enable omnidirectional light absorption, and bimodal pores facilitate ion diffusion to suppress salt deposits. This BSE exhibits an evaporation rate of 2.3 kg m-2 h-1 and efficiency of 93% under 1 sun. The multiple advantages of high efficiency and salt resistance make BSE available for future practical sewage purification and desalination applications.

Detection of maternal uniparental disomy 9 in association with low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with intrauterine growth restriction, abnormal first-trimester screening result (low PAPP-A and low PlGF), maternal preeclampsia and a favorable outcome.

OBJECTIVE: We present detection of maternal uniparental disomy (UPD) 9 in association with low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR), an abnormal first-trimester maternal serum screening result, abnormal non-invasive prenatal testing (NIPT), maternal preeclampsia and a favorable outcome. CASE REPORT: A 37-year-old, primigravid woman underwent first-trimester maternal serum screening and NIPT at 11 weeks of gestation, which revealed a gene dosage increase in chromosome 9 and low levels of plasma protein-A (PAPP-A) and placental growth factor (PlGF) in maternal blood. The woman underwent amniocentesis at 16 weeks of gestation, which revealed a karyotype of 47,XX,+9[4]/46,XX[35] in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (9) × 3 [0.14] (X) × 2, compatible with mosaic trisomy 9. The parental karyotypes were normal. Repeat amniocentesis was performed at 20 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+9[1]/46,XX[23]. The uncultured amniocytes had a mosaic trisomy 9 level of 10.7% (12/112 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 9 level of 10-14% (log2 ratio = 0.1) by aCGH, and maternal uniparental isodisomy 9 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR, and the mother had preeclampsia. At 29 weeks of gestation, a 1054-g phenotypically normal baby was delivered because of preterm labor. The cord blood and umbilical cord had the karyotype of 46, XX and maternal UPD 9 and isodisomy 9, while the placenta had trisomy 9 of maternal origin. Postnatal FISH anlaysis on 101 buccal mucosal cells and 100 urinary cells at age three months detected no trisomy 9 signals. The baby was doing well at age six months. CONCLUSION: Pregnancy with low-level mosaic trisomy 9 and maternal UPD 9 at amniocentesis can be associated with IUGR, maternal preeclampsia and a favorable outcome. Fetuses with maternal UPD 9 can be associated with an abnormal NIPT result concerning chromosome 9, an abnormal first-trimester maternal serum screening result (low PAPP-A and low PlGF) and mosaic trisomy 9 at amniocentesis.

Prenatal diagnosis of partial monosomy 8p (8p23.2→pter) and partial trisomy 15q (15q21.2→qter) and incidental detection of a familial chromosome translocation of paternal origin in a pregnancy associated with increased nuchal translucency and an abnormal maternal serum screening result.

OBJECTIVE: We present partial monosomy 8p (8p23.2→pter) and partial trisomy 15q (15q21.2→qter) and incidental detection of a familial chromosome translocation of paternal origin in a pregnancy associated with increased nuchal translucency (NT) and an abnormal maternal serum screening result. CASE REPORT: A 29-year-old primigravid woman underwent chorionic villus sampling (CVS) at 13 weeks of gestation because of an increased NT thickness of 3.2 mm at 12 weeks of gestation and an abnormal maternal serum screening for Down syndrome result with a calculated risk of 1/29. Her husband was 33 years old, and there was no family history of congenital malformations. CVS revealed a derived chromosome 8 or der(8). Cytogenetic analysis of the parents revealed a karyotype of 46,XY,t(8;15)(p21.3;q13) in the father and a karyotype of 46,XX in the mother. The CVS result was 46,XY,der(8)t(8;15)(p21.3;q13)pat. The woman requested for amniocentesis at 16 weeks of gestation. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a result of arr 8p23.3p23.2 (191,530-2,625,470) × 1.0, arr 15q21.2q26.3 (50,903,432-102,338,129) × 3.0 with a 2.434-Mb deletion of 8p23.3-p23.2 including DLGAP2, CLN8 and ARHGEF10, and a 51.435-Mb duplication of 15q21.2-q26.3 including CYP19A1 and IGF1R. Conventional cytogenetic analysis of cultured amniocytes revealed the result of 46,XY,der(8) t(8;15)(p23.2;q21.2)pat in the fetus. The pregnancy was subsequently terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism. CONCLUSION: Maternal serum screening and NT screening may incidentally detect familial unbalanced reciprocal translocations, and aCGH analysis is useful for a precise determination of the breakpoints of the translocation and the involvement of the related genes under such a circumstance.

Prenatal diagnosis of maternal uniparental disomy 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction in the fetus.

OBJECTIVE: We present prenatal diagnosis of maternal uniparental disomy (UPD) 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction (IUGR) in the fetus. CASE REPORT: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XX,+16[2]/46,XX[54]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 14% mosaicism for trisomy 16 and a paternally inherited 319-kb microdeletion of 15q11.2 encompassing the genes of TUBGCP5, CYFIP1, NIPA2 and NIPA1. Prenatal ultrasound revealed persistent left superior vena cava, pericardial effusion and severe IUGR. Cordocentesis at 23 weeks of gestation revealed a karyotype of 46,XX, but polymorphic DNA marker analysis revealed maternal UPD 16. Repeat amniocentesis was performed at 27 weeks of gestation and revealed a karyotype of 46, XX in 21/21 colonies. Molecular cytogenetic analysis on uncultured amniocytes revealed 22.4% mosaicism (26/116 cells) for trisomy 16 on interphase fluorescence in situ hybridization (FISH) analysis, and 20% mosaicism for trisomy 16 on aCGH. Polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods revealed maternal UPD 16. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism and severe IUGR. The umbilical cord had a karyotype of 47,XX,+16[28]/46,XX[16]. Polymorphic DNA marker analysis on placenta confirmed a maternal origin of trisomy 16. CONCLUSION: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may present in mosaic trisomy 16 at amniocentesis. Prenatal diagnosis of mosaic trisomy 16 should alert the association of maternal UPD 16 which may be associated with congenital heart defects and severe IUGR on prenatal ultrasound.

Prenatal diagnosis of low-level mosaicism for a small supernumerary marker chromosome derived from chromosome 9q (9q13-q21.33) in a pregnancy with a favorable outcome, and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

OBJECTIVE: We present prenatal diagnosis of low-level mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 9q (9q13-q21.33) in a pregnancy with a favorable outcome, and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes. CASE REPORT: A 36-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis on cultured amniocytes revealed a karyotype of 46,XY in 20/20 colonies. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed 30% mosaicism for a de novo 20.3-Mb gene dosage increase at 9q13-q21.33. Repeat amniocentesis and cordocentesis were performed at 21 weeks of gestation. Cytogenetic analysis on cord blood revealed a karyotype of 47,XY,+mar [3]/46,XY [37]. aCGH analysis of cord blood revealed 7.5% mosaicism for a 17.15-Mb gene dosage increase at 9q21.11-q21.33. aCGH analysis of uncultured amniocytes revealed 11.7% mosaicism for a 17.15-Mb gene dosage increase at 9q21.11-q21.33. Polymorphic DNA marker analysis excluded uniparental disomy 9. The parental karyotypes were normal. The pregnancy was carried to 37 weeks of gestation, and a 2955-g phenotypically normal male baby was delivered. At birth, the cord blood had a karyotype of 47,XY,+mar [3]/46,XY [37], the placenta had a karyotype of 47,XY,+mar [10]/46,XY [30], and the umbilical cord had a karyotype of 47,XY,+mar [14]/46,XY [36]. aCGH analysis on the DNA extracted from cord blood at birth revealed no genomic imbalance. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells at age two months detected 3.8% (4/106 cells) mosaicism for the sSMC, compared with 2% (2/100 cells) in the normal control. The neonate had normal physical development at age two months. CONCLUSION: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may exist in the pregnancy with fetal mosaic sSMC. Low-level mosaicism for an sSMC derived from chromosome 9q13-q21.33 at prenatal diagnosis can be associated with a favorable outcome in the fetus.