Search

Abstract Backgroud A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. Methods In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. Results Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

Abstract Background The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. Methods Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. Results The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. Conclusion Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. Simple summary The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Abstract Objective To assess prenatal diagnosis and pregnancy outcomes in twin pregnancies where one fetus has nuchal translucency (NT) above the 95th percentile. Method In this retrospective analysis, 130 twin pregnancies (260 fetuses) in which one twin had an NT measurement above the 95th percentile while that of the other twin was normal were analyzed. Prenatal diagnostic results such as G bands, chromosomal microarray analysis, ultrasound findings, and pregnancy outcomes were reviewed. Results Karyotype analysis and CMA results revealed that 15 (15.6 percent, 15/96) fetuses exhibited chromosomal abnormalities and that 13 fetuses were Variant of Uncertain Significance. Chromosome abnormalities were detected at a rate of 8.9% (5/56) in the DCT group and 25.0% (10/40) in the MCT group (p = 0.033, X2 = 4.571). 2 fetuses in DCT (3.9 percent, 2/51) and 4 fetuses in MCT (13.3 percent, 4/30) (p = 0.187) revealed structural abnormalities among the cases with normal prenatal diagnosis. Fetuses in the DCT group had an overall survival rate of 75.4 percent (95/126), whereas those in the MCT group had a survival rate of 60.4 percent (81/134) (p = 0.01, X2 = 6.636). According to the findings of Logistics regression analysis, NT thickening, maternal age and method of conception were all significant risk factors for chromosome abnormalities. Conclusion In twin pregnancies with one fetus with NT above the 95th percentile, the prevalence of fetal structural abnormalities of the MCT group and the DCT group were comparable. Pregnant women’s age and mode of pregnancy are risk factors for chromosomal abnormalities.

Abstract Background A novel CT-linac (kilovolt fan-beam CT-linac) has been introduced into total marrow and lymphoid irradiation (TMLI) treatment. Its integrated kilovolt fan-beam CT (kV FBCT) can be used not only for image guidance (IGRT) but also to re-calculate the dose. Purpose This study reported our clinical routine on performing TMIL treatment on the CT-linac, as well as dose distribution comparison between planned and re-calculated based on IGRT FBCT image sets. Methods 11 sets of data from 5 male and 6 female patients who had underwent the TMLI treatment with uRT-linac 506c were selected for this study. The planning target volumes consist of all skeletal bones exclusion of the mandible and lymphatic sanctuary sites. A planned dose of 10 Gy was prescribed to all skeletal bones exclusion of the mandible in two fractions and 12 Gy in two fractions was prescribed to lymphatic sanctuary sites. Each TMLI plan contained two sub-plans, one dynamic IMRT for the upper body and the other VMAT for the lower extremity. Two attempts were made to obtain homogeneous dose in the overlapping region, i.e., applying two plans with different isocenters for the treatment of two fractions, and using a dose gradient matching scheme. The CT scans, including planning CT and IGRT FBCT, were stitched to a whole body CT scan for dose distribution evaluation. Results The average beam-on time of Planupper is 30.6 min, ranging from 24.9 to 37.5 min, and the average beam-on time of Planlower is 6.3 min, ranging from 5.7 to 8.2 min. For the planned dose distribution, the 94.79% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 94.68% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). For the re-calculated dose distribution, the 92.17% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 90.07% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). The results showed that there is a significant difference (p 0.05) between planned dose and re-calculated dose on selected organs, except for right lens (p

Abstract Objective To evaluate the prenatal and perinatal outcome of fetuses with extremely large nuchal translucency (eNT) thickness (≥ 6.5 mm). Methods 193 (0.61%) singleton fetuses with eNT were retrospectively included. Anomaly scan, echocardiography, and chromosomal and genetic test were included in our antenatal investigation. Postnatal follow-up was offered to all newborns. Results Major congenital anomalies included congenital heart defect (32.6%, 63/193), hydrops fetalis (13.5%, 26/193), omphalocele (9.3%, 18/193), and skeletal dysplasia (7.8%, 15/193) et al. Abnormal karyotype was identified in 81/115 (70.4%) cases including Turner syndrome (n = 47), Trisomy 18 (n = 17), Trisomy 21 (n = 9), and Trisomy 13 (n = 3). Chromosomal microarray analysis provided informative results with 3.6% (1/28) incremental diagnostic yield over conventional karyotyping. The diagnostic yield of exome sequencing is 10.0% (2/20). There was no significant increase [Odds Ratio (OR) = 1.974; 95% confidence interval 0.863–4.516; P = 0.104] in the incidence of chromosomal defects despite the presence of other structural anomalies. Only 13 fetuses were successfully followed up and survived at term, no one was found with developmental delay or mental retardation. Conclusions Extremely large NT has a high risk of chromosomal abnormality. CMA and ES improve chromosomal genomic and genetic diagnosis of fetal increased NT. When cytogenetic analysis and morphology assessment are both normal, the outcome is good.

Hemophilia, an X-linked recessive disorder, is characterized by spontaneous or trauma-induced prolonged bleeding. It is classified as hemophilia A when caused by variants in the F8 gene, and hemophilia B when caused by F9 variants. Few studies have described hemophilia variants in the Chinese population. This study aimed to investigate the clinical and genetic profiles of 193 hemophilia patients from southern China. Utilizing Sanger sequencing, multiplex ligation-dependent probe amplification, gap detection, long-range PCR, and multiplex PCR, we identified both F8 and F9 gene variants. Pregnant women with a history of hemophilia A offspring underwent amniocentesis or villus sampling for the variant detection. Variants in F8 and F9 were pinpointed in 183 patients, with 26 being novel discoveries. Notably, genetic testing was absent in the initial evaluation of 133 out of 161 patients, leading to a protracted average definitive diagnosis timeline of 2 years. Remarkably, two hemophilia A cases with anticipated severe phenotypes due to protein-truncating variants presented with only moderate or mild clinical manifestations. Among the 40 fetuses tested, 34 were males, with 17 exhibiting hemizygous variants in the F8 gene. Our results contribute to the broader understanding of F8 and F9 variant spectrum and highlight the underuse of genetic analyses in southern China.

Graphite anode materials and carbonate electrolyte have been the top choices for commercial lithium-ion batteries (LIBS) for a long time. However, the uneven deposition and stripping of lithium cause irreversible damage to the graphite structure, and the low flash point and high flammability of the carbonate electrolyte pose a significant fire safety risk. Here, we proposed a multifunctional electrolyte additive diphenylphosphoryl azide (DPPA), which can construct a solid electrolyte interphase (SEI) with high ionic conductivity lithium nitride (Li3N) to ensure efficient transport of Li+. This not only protects the artificial graphite (AG) electrode but also inhibits lithium dendrites to achieve excellent electrochemical performance. Meanwhile, the LIBS with DPPA offers satisfactory flame retardancy performance. The AG//Li half cells with DPPA-0.5M can still maintain a specific capacity of about 350 mAh/g after 200 cycles at 0.2 C. Its cycle performance and rate performance were better than commercial electrolyte (EC/DMC). After cycling, the microstructure surface of the AG electrode was complete and flat, and the surface of the lithium metal electrode had fewer lithium dendrites. Importantly, we found that the pouch cell with DPPA-0.5M had low peak heat release rate. When exposed to external conditions of continuous heating, DPPA significantly improved the fire safety of the LIBS. The research of DPPA in lithium electrolyte is a step towards the development of safe and efficient lithium batteries.

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.

Objective: This retrospective study aims to evaluate the utility of exome sequencing (ES) in identifying genetic causes of congenital orofacial clefts (OFCs) in fetuses with or without other structural abnormalities, and to further explore congenital OFCs genetic causes.Methods: The study enrolled 107 singleton pregnancies diagnosed with fetal OFCs between January 2016 and May 2022, and categorized them into two groups: isolated cleft lip and/or palate (CL/CP) and syndromic CL/CP. Cases with positive karyotyping and chromosomal microarray analysis results were excluded. Whole-exome sequencing was performed on eligible fetuses and their parents. Monogenic variants identified by ES and perinatal outcomes were recorded and evaluated during postnatal follow-up.Results: Clinically significant variants were identified in 11.2% (12/107) of fetuses, with no significant difference in detection rate between the isolated CL/CP group and the syndromic CL/CP group (8/83, 9.6% vs. 4/24, 16.7%, p = 0.553). Additionally, sixteen (16/107, 15.0%) fetuses had variants of uncertain significance. We identified 12 clinically significant variations that correlated with clinical phenotypes in 11 genes from 12 fetuses, with CHD7 being the most frequently implicated gene (n = 2). Furthermore, we observed a significant difference in termination rates and survival rates between the isolated CL/CP and syndromic CL/CP groups (41.0% vs. 70.8% and 56.6% vs. 20.8%, p < 0.05 for both).Conclusion: Based on our findings, it is clear that ES provides a significant increase in diagnostic yield for the molecular diagnosis of congenital OFCs, thereby substantially improving the existing prenatal diagnostic capabilities. This study also sheds light on seven novel pathogenic variants, broadening our understanding of the genetic underpinnings of OFCs and expanding the disease spectrums of relevant genes.

Congenital heart disease (CHD) is a serious condition with unknown etiology. In a recent study, a compound heterozygous mutation (c.3526C > T [p.Arg1176Trp] and c.4643A > G [p.Asp1548Gly]) in the ASXL3 gene was identified, which is associated with CHD. This mutation was overexpressed in HL-1 mouse cardiomyocyte cells, leading to increased cell apoptosis and decreased cell proliferation. However, whether this effect is mediated by long noncoding RNAs (lncRNAs) is yet to be determined. We identified the differences among lncRNA and mRNA profiles in mouse heart tissues using sequencing to explore this issue. We detected HL-1 cell proliferation and apoptosis through CCK8 and flow cytometry. Fgfr2, lncRNA, and Ras/ERK signaling pathway expressions were evaluated using quantitative real time polymerase chain reaction (qRT-PCR) and western blot (WB) assays. We also conducted functional investigations by silencing lncRNA NONMMUT063967.2. The sequencing revealed significant changes in lncRNA and mRNA profiles, with the expression of lncRNA NONMMUT063967.2 being significantly promoted in the ASXL3 gene mutations group (MT) while the expression of Fgfr2 being downregulated. The in vitro experiments showed that ASXL3 gene mutations inhibited the proliferation of cardiomyocytes and accelerated cell apoptosis by promoting the expression of lncRNAs (NONMMUT063967.2, NONMMUT063918.2, and NONMMUT063891.2), suppressing the formation of FGFR2 transcripts, and inhibiting the Ras/ERK signaling pathway. The decrease in FGFR2 had the same effect on the Ras/ERK signaling pathway, proliferation, and apoptosis in mouse cardiomyocytes as ASXL3 mutations. Further mechanistic studies revealed that suppression of lncRNA NONMMUT063967.2 and overexpression of FGFR2 reversed the effects of the ASXL3 mutations on the Ras/ERK signaling pathway, proliferation, and apoptosis in mouse cardiomyocytes. Therefore, ASXL3 mutation decreases FGFR2 expression by upregulating lncRNA NONMMUT063967.2, inhibiting cell proliferation and promoting cell apoptosis in mouse cardiomyocytes.

Abstract Background Exome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain limited in practice. Herein, we report our experience implementing prenatal ES (pES) in a large cohort of fetuses with anomalies detected by ultrasonography using a hospital-based in-house multidisciplinary team (MDT) facilitated by a three-step genotype-driven followed by phenotype-driven analysis framework. Methods We performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. The diagnostic efficiency and its correlation to organ systems involved, phenotypic spectrum, and the clinical impacts of pES results on pregnancy outcomes were analyzed. Results A genotype-driven followed by phenotype-driven three-step approach was carried out in all trio pES. Step 1, a genotype-driven analysis resulted in a diagnostic rate of 11.6% (187/1618). Step 2, a phenotype-driven comprehensive analysis yielded additional diagnostic findings for another 28 cases (1.7%; 28/1618). In the final step 3, data reanalyses based on new phenotypes and/or clinical requests found molecular diagnosis in 14 additional cases (0.9%; 14/1618). Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p

Background: Thalassemia is the most prevalent monogenic disorder caused by an imbalance between the α- and β-globin chains as a result of pathogenic variants in the α- or β-globin genes. Novel or complex structural changes in globin genes are major hurdles for genetic consulting and prenatal diagnosis.Methods: From 2020 to 2022, genetic analysis was performed on 1,316 families suspected of having children with thalassemia major, including 42 pregnant couples suspected of being thalassemia carriers with rare variants. Multiple techniques including multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, targeted next-generation sequencing, and single-molecule real-time (SMRT) sequencing were used to diagnose rare thalassemia.Results: The rate of prenatal diagnosis for rare thalassemia variants was 3.19% (42/1,316). The most prevalent alleles of α- and β-thalassemia are Chinese Gγ(Aγδβ)0and -- THAI deletion. In addition, ten rare complex genotypes include one Chinese Gγ(Aγδβ)0 deletion combined with HBG1-HBG2 fusion, two rare deletions at HBB gene (hg38, Chr11: 5224211-5232470, hg38, Chr11: 5224303-5227790), one complete 7,412 bp fusion gene for anti-Lepore Hong Kong, two complex rearrangements of the α-globin gene cluster, two novel duplications, and two rare large deletions in the α-globin gene cluster.Conclusion: Accurate gene diagnosis for probands with combined molecular biology techniques is the key to prenatal diagnosis of rare thalassemia.

Abstract Background There are a few literature reports of prenatal ultrasound manifestations of Williams-Beuren syndrome. We aimed to explore the prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis and describe the prenatal ultrasound performance of this syndrome. Methods In this retrospective study, we reported eight cases of Williams-Beuren syndrome diagnosed at our prenatal diagnostic center from 2016 to 2021. We systematically reviewed clinical data from these cases, including indications for invasive testing, sonographic findings, QF-PCR results, chromosomal microarray analysis results, and pregnancy outcomes. Results In this study, the common ultrasound features were ventricular septal defect (37.5%), intrauterine growth retardation (25%), and aortic coarctation (25%). Moreover, all patients were found to have a common deletion in the Williams-Beuren syndrome chromosome region at the 7q11.23 locus, which contained the elastin gene. Deletion sizes ranged from 1.42 to 2.07 Mb. Seven parents asked for termination of pregnancy, and one patient was lost to follow-up. Conclusions This study is the most extensive prenatal study using chromosomal microarray analysis technology for detailed molecular analysis of Williams-Beuren syndrome cases. We reported three cases combined with first-reported ultrasound manifestations. Case 1 was concomitant with multicystic dysplastic kidney and duodenal atresia combined with case 3. Notably, case 4 was combined with multiple cardiovascular malformations: Tetralogy of Fallot, right aortic arch, and supravalvar aortic stenosis. These manifestations expand the intrauterine ultrasound phenotype of Williams-Beuren syndrome in previous literature reports.

Background: Microcephaly is common in patients with neuropsychiatric problems, and it is usually closely related to genetic causes. However, studies on chromosomal abnormalities and single-gene disorders associated with fetal microcephaly are limited.Objective: We investigated the cytogenetic and monogenic risks of fetal microcephaly and evaluated their pregnancy outcomes.Methods: We performed a clinical evaluation, high-resolution chromosomal microarray analysis (CMA), and trio exome sequencing (ES) on 224 fetuses with prenatal microcephaly and closely followed the pregnancy outcome and prognosis.Results: Among 224 cases of prenatal fetal microcephaly, the diagnosis rate was 3.74% (7/187) for CMA and 19.14% (31/162) for trio-ES. Exome sequencing identified 31 pathogenic or likely pathogenic (P/LP) single nucleotide variants (SNVs) in 25 genes associated with fetal structural abnormalities in 37 microcephaly fetuses; 19 (61.29%) of which occurred de novo. Variants of unknown significance (VUS) was found in 33/162 (20.3%) fetuses. The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3. The live birth rate of fetal microcephaly in the syndromic microcephaly group was significantly higher than that in the primary microcephaly group [62.9% (117/186) vs 31.56% (12/38), p = 0.000].Conclusion: We conducted a prenatal study by conducting CMA and ES for the genetic analysis of fetal microcephaly cases. CMA and ES had a high diagnostic rate for the genetic causes of fetal microcephaly cases. In this study, we also identified 14 novel variants, which expanded the disease spectrum of microcephaly-related genes.

Aims: To compared the amniotic fluid and vaginal microbiota of pregnant women, who developed gestational diabetes mellitus to those who did not, and explored if any differences exist in the composition and functional genes of their amniotic fluid and vaginal microbiota. Methods: We compared the amniotic fluid and vaginal microbiota of five GDM patients and five non-GDM pregnant women in the third trimester of pregnancy by using metagenomics, and analyzed the characteristics, functions, and differences between two groups. Results: The analysis of the amniotic fluid showed significant differences in genus and species. In contrast, there was no significant difference in vaginal microbial community structure between two groups. The alpha diversity in the GDM group was higher than the control, but the difference was not statistically significant. There was a statistically significant difference in the species-level beta-diversity measured by Bray–Curtis distance of the amniotic fluid communities between two groups, while no significant differences were observed in the vaginal microbiota. Regarding the functions, we observed that the microbial communities of the amniotic fluid and vaginal secretions were involved in the regulation of a variety of host metabolic pathways, including carbohydrate metabolism, membrane transport, energy, amino acid metabolism, nucleotide metabolism, etc. No significant differences were observed between two groups, but different sites exist. Conclusion: The amniotic fluid of this study was discovered to have a heterogeneous, albeit small in number, community of microorganisms.Our research suggests that gestational diabetes has a very limited impact on the amniotic fluid and vaginal microbiome. The composition and the functions of the microbiota at different sites are different.

Model systems to study SARS-CoV-2 infection are required to better understand the immune response. Here the authors use a lung and macrophage co-culture system by differentiation of human pluripotent stem cells to better understand the phenotype and gene expression changes in host lung cells and macrophages after SARS-CoV-2 infection in vitro.

As an important part of the space-integrated-ground information network, the satellite communication system has become a research hotspot.The system modeling language (SysML), which is the most popular digital design language, was adopted to analyzing requirements, decomposing functions and synthesizing designs of the satellite communication system.The verifi cation result indicated that the architecture and the service process of the satellite communication system designed in this paper is of robustness to some degree.By used SysML in the digital design of satellite communication system, this research supported the key technologies’ design and verifi cation in the satellite communication system.

Balanced chromosomal abnormalities (BCAs) are the most common chromosomal abnormalities and the frequency of congenital abnormalities is approximately twice as high in newborns with a de novo BCA, but a prenatal diagnosis based on BCAs is subject to evaluation. To detect translocation breakpoints and conduct a prenatal diagnosis, we performed whole-genome sequencing (WGS) in 21 subjects who were found BCAs, 19 balanced chromosome translocations and two inversions, in prenatal screening. In 16 BCAs on non-N-masked regions (non-NMRs), WGS detected 13 (81.2%, 13/16) BCAs, including all the inversions. All the breakpoints of 12 (12/14) cases of sufficient DNA were confirmed by Sanger sequencing. In 13 interrupted genes, CACNA1E (in case 12) and STARD7 (in case 17) are known causative and PDCL was found in subject (case 11) with situs inversus for the first time. Case 12 with abnormal ultrasound reached a definitive genetic diagnosis of CACNA1E-disease, while STARD7 exon deletion has never been found causative in patients. WGS provides the possibility of prenatal diagnosis in fetuses with BCAs, and its clinical significance also lies in providing data for postnatal diagnosis.

ObjectiveTo evaluate the utility of chromosomal microarray analysis (CMA) in fetuses with isolated ventricular septal defect (VSD) and to explore the favorable factors for predicting spontaneous closure of defects.MethodsThe study included 436 singleton pregnancies seen at a referral prenatal diagnosis center, between January 2016 and May 2020, of which 168 fetuses with isolated VSD were diagnosed in the prenatal setting. VSD was classified as an isolated VSD whether it had ultrasound soft markers or not. All patients underwent testing employing quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategies, mainly in amniotic fluid and umbilical blood samples. Rates of chromosomal abnormalities were compared by subgroups of isolated VSD (muscular or perimembranous). Binary logistic regression analysis was performed to predict the independent determinants of spontaneous closure by 2 years.ResultsOverall, the CMA identified clinically significant copy number variations (CNVs) in 7/168 (4.2%) fetuses and variants of unknown significance (VOUS) in 15/168 (8.9%). Muscular and perimembranous VSDs were found in 53.6 and 46.4%, respectively. Clinically significant relevant subchromosomal aberrations were revealed in seven (9.0%) perimembranous VSDs compared with none in 90 muscular defects (P < 0.01). The median initial size of the defect in the muscular VSDs was 2.2(1.8–2.7) mm, as compared to that of 2.8 (2.2–3.2) mm in the perimembranous VSDs group (p = 0.000). In muscular vs. perimembranous VSDs, spontaneous closure occurred more frequently and earlier [40.0 vs. 15.4% in utero (p = 0.000), 61.1 vs. 30.8% at 1-year (p = 0.000), and 75.6 vs. 42.3% at 2-year (P = 0.000)]. Postnatal surgical closure was warranted in 4/90 (4.4%) of the infants with muscular VSDs, as compared to 29/71 (40.8%) with perimembranous defects (p = 0.000). Furthermore, isolated muscular type VSD, smaller defect size, and maternal age of less than 35 years are all positive predictors of spontaneous closure of the defects.ConclusionThis study highlighted the value of microarray for unbalanced subchromosomal abnormalities in fetuses with isolated VSD, particularly in the perimembranous defects. The detection of an isolated muscular VSD prenatally may be considered a benign or likely benign finding; in contrast, for perimembranous VSD, a prenatal CMA should be offered.

A global survey indicates that genetic syndromes affect approximately 8% of the population, but most genetic diagnoses can only be performed after babies are born. Abnormal facial characteristics have been identified in various genetic diseases; however, current facial identification technologies cannot be applied to prenatal diagnosis. We developed Pgds-ResNet, a fully automated prenatal screening algorithm based on deep neural networks, to detect high-risk fetuses affected by a variety of genetic diseases. In screening for Trisomy 21, Trisomy 18, Trisomy 13, and rare genetic diseases, Pgds-ResNet achieved sensitivities of 0.83, 0.92, 0.75, and 0.96, and specificities of 0.94, 0.93, 0.95, and 0.92, respectively. As shown in heatmaps, the abnormalities detected by Pgds-ResNet are consistent with clinical reports. In a comparative experiment, the performance of Pgds-ResNet is comparable to that of experienced sonographers. This fetal genetic screening technology offers an opportunity for early risk assessment and presents a non-invasive, affordable, and complementary method to identify high-risk fetuses affected by genetic diseases. Additionally, it has the capability to screen for certain rare genetic conditions, thereby enhancing the clinic’s detection rate.

Abstract Background Noninvasive prenatal testing (NIPT) of recessive monogenic diseases depends heavily on knowing the correct parental haplotypes. However, the currently used family-based haplotyping method requires pedigrees, and molecular haplotyping is highly challenging due to its high cost, long turnaround time, and complexity. Here, we proposed a new two-step approach, population-based haplotyping-NIPT (PBH-NIPT), using α-thalassemia and β-thalassemia as prototypes. Methods First, we deduced parental haplotypes with Beagle 4.0 with training on a large retrospective carrier screening dataset (4356 thalassemia carrier screening-positive cases). Second, we inferred fetal haplotypes using a parental haplotype-assisted hidden Markov model (HMM) and the Viterbi algorithm. Results With this approach, we enrolled 59 couples at risk of having a fetus with thalassemia and successfully inferred 94.1% (111/118) of fetal alleles. We confirmed these alleles by invasive prenatal diagnosis, with 99.1% (110/111) accuracy (95% CI, 95.1–100%). Conclusions These results demonstrate that PBH-NIPT is a sensitive, fast, and inexpensive strategy for NIPT of thalassemia.

Abstract Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6−/−) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6−/−-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6−/−-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6−/−-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence.

The distribution of the microbiome in women with advanced maternal age (AMA) is poorly understood. To gain insight into this, the vaginal and gut microbiota of 62 women were sampled and sequenced using the 16S rRNA technique. These women were divided into three groups, namely, the AMA (age ≥ 35 years, n = 13) group, the non-advanced maternal age (NMA) (age < 35 years, n = 38) group, and the control group (non-pregnant healthy women, age >35 years, n = 11). We found that the alpha diversity of vaginal microbiota in the AMA group significantly increased. However, the beta diversity significantly decreased in the AMA group compared with the control group. There was no significant difference in the diversity of gut microbiota among the three groups. The distributions of microbiota were significantly different among AMA, NMA, and control groups. In vaginal microbiota, the abundance of Lactobacillus was higher in the pregnant groups. Bifidobacterium was significantly enriched in the AMA group. In gut microbiota, Prevotella bivia was significantly enriched in the AMA group. Vaginal and gut microbiota in women with AMA were noticeably different from the NMA and non-pregnant women, and this phenomenon is probably related to the increased risk of complications in women with AMA.

Objective: To evaluate the utility of a chromosomal microarray (CMA) in fetuses with isolated fetal growth restriction (FGR) and explore risk factors for the prediction of chromosomal aberration and perinatal adverse outcomes.Method: This study included 271 fetuses of estimated fetal weight less than the 3rd percentile without other structural malformation. Early-onset and late-onset FGR were defined as gestational weeks less than 32 weeks and more than 32 weeks respectively. These patients underwent quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategy. Chromosomal anomalies were compared after stratified analysis by the early-onset and the late-onset FGR, including the absence or presence of ultrasound soft markers, abnormal amniotic fluid, abnormal umbilical Doppler, and gestational disorders. The follow-up time was within 1 year after birth. Logistic regression was used to seek risk predictors of chromosomal aberration and perinatal adverse outcomes for isolated FGR.Results: The CMA identified clinically significant variants in 18/271 (6.6%) fetuses, and variants of unknown significance (VOUS) in 15/271 (5.5%) fetuses. Stratified analysis showed that there was a higher incidence of clinically significant variants in fetuses with the early-onset FGR compared with late-onset FGR (8.7%, 17/195 vs. 1.3%, 1/76, p < 0.05). Regression analysis showed that early gestational age (GA) at diagnosis of FGR was the major risk factor for chromosomal aberration (OR = 0.846). By variable regression analysis, early GA at diagnosis and decreased estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia could all increase the risk of adverse outcomes of isolated FGR including intra-uterine fetal death (IUFD), termination of pregnancy (TOP), and preterm birth in pregnancies with FGR.Conclusion: This study emphasized the value of microarrays for unbalanced genomic variants in fetuses with isolated FGR, especially since the gestational age of nullipara was less than 32 weeks. Perinatal adverse outcomes of isolated FGR were influenced by multiple factors including GA and estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia.

L1 cell adhesion molecule is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. Pathogenic mutations of L1CAM can cause L1 syndrome, referred to as a variety of disease spectrums characterized by hydrocephalus. In the present study, we reported two novel variants of L1CAM in two unrelated Chinese families with fetal hydrocephalus history. The woman of family 1, with three consecutive adverse birth histories of male fetuses with hydrocephalus, was identified by an exome sequence with a heterozygous mutation in the L1CAM gene, NM_000425.4: c.1696_1703 + 14del (p. S566Vfs*35), which was predicted to be pathogenic. It is predicted to disrupt RNA splicing and likely leads to an absent or disrupted protein product. In family 2, the mother, previously with once a voluntary termination of pregnancy owning to the fetus with hydrocephalus, was pregnant with a fetus with hydrocephalus in her second pregnancy. After fetal blood sampling, a pathogenic deletion of 1511bp in L1CAM, chromosome X: 153131395-153132905(hg19/GRCh37)/NM_000425.4: c.2043_2432-121del1511 leading to deletion of fibronectin type-III repeats I-II, was identified in the fetus with hydrocephalus inherited from the mother by an exome sequence. On her third pregnancy, a healthy female fetus was born without the L1CAM variant by preimplantation genetic testing for the monogenic disorder. This study emphasizes the importance of ultrasonic manifestation and family history of fetal hydrocephalus for L1CAM diagnosis. Our study expands the genotypes of L1CAM and aids the genetic counseling of fetal hydrocephalus and even preimplantation genetic testing for the monogenic disorder.

Abstract Background Individuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling. Methods A total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects. Results A total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δβ-thalassemia, including Chinese Gγ (Aγδβ)0-thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore–Boston–Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying β-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the Aγ-197C-T heterozygous state. It is difficult to discriminate between Chinese Gγ (Aγδβ)0-thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis. Conclusions This study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia.

Beta-thalassemia (BT) is a hereditary disease caused by abnormal hemoglobin synthesis with consequent ineffective erythropoiesis. Patients with thalassemia major are dependent on long-term blood transfusions with associated long-term complications such as iron overload (IO). This excess iron can result in tissue damage, impaired organ function, and increased morbidity. Growing evidence has demonstrated that IO contributes to impairment of the bone marrow (BM) microenvironment that largely impacts the function of BM mesenchymal stem cells, hematopoietic stem cells, and endothelial cells. In this article, we review recent progress in the understanding of iron metabolism and the perniciousness induced by IO. We highlight the importance of understanding the cross-talk between BM stem cells and the BM microenvironment, particularly the pathological effect of IO on BM stem cells and BT-associated complications. We also provide an update on recent novel therapies to cure transfusion-dependent beta-thalassemia and iron overload-induced complications for their future clinical application.

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder associated with mutations of the ABCD1 gene that encodes a peroxisomal transmembrane protein. It results in accumulation of very long chain fatty acids in tissues and body fluid. Along with other factors such as epigenetic and environmental involvement, ABCD1 mutation-provoked disorders can present different phenotypes including cerebral adrenoleukodystrophy (cALD), adrenomyeloneuropathy (AMN), and peripheral neuropathy. cALD is the most severe form that causes death in young childhood. Bone marrow transplantation and hematopoietic stem cell gene therapy are only effective when performed at an early stage of onsets in cALD. Nonetheless, current research and development of novel therapies are hampered by a lack of in-depth understanding disease pathophysiology and a lack of reliable cALD models. The Abcd1 and Abcd1/Abcd2 knock-out mouse models as well as the deficiency of Abcd1 rabbit models created in our lab, do not develop cALD phenotypes observed in human beings. In this review, we summarize the clinical and biochemical features of X-ALD, the progress of pre-clinical and clinical studies. Challenges and perspectives for future X-ALD studies are also discussed.

Objective: In this study, we aimed to examine the changes in the composition of vaginal and gut microbiota during the third trimester of pregnancy among women who delivered preterm. To further understand the relationship of these changes to preterm birth, we analyzed the microecology of vaginal and gut microbiota in mothers, as well as oral and gut microbiota in their newborns, and then compared the microecological characteristics of the microbiome at different body sites between the mothers and their newborns, as well as between the mothers and between the newborns from different groups. Methods: In total, 26 women who delivered at Zhujiang Hospital, Southern Medical University (China) from July 2020 to January 2021 were categorized into the preterm and term groups. A blank swab and laboratory air and water samples were collected as part of the control group. We collected maternal vaginal and rectal samples, as well as neonatal oral and rectal samples. Total DNA from different parts of the swabs was extracted and sequenced using the 16s rRNA technique. Then, the data was analyzed using bioinformatics and statistical analysis. Results: The abundance and alpha diversity of vaginal microbiota in the preterm group was found to be higher, but the difference was not statistically significant. There were significant differences in beta diversity of vaginal microbiota between the two groups (p ​

Background and methods: Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution single nucleotide polymorphism (SNP) arrays to investigate 489 patients with unexplained DD/ID in whom standard karyotyping analyses showed normal karyotypes. This study aimed to assess the usefulness of CMA for clinical diagnostic testing in the Chinese population. Results: A total of 489 children were classified into three groups: isolated DD/ID (n = 358), DD/ID with epilepsy (n = 49), and DD/ID with other structural anomalies (n = 82). We identified 126 cases (25.8%, 126/489) of pathogenic copy number variants (CNVs) by CMA, including 89 (24.9%, 89/358) with isolated DD/ID, 13 (26.5%, 13/49) with DD/ID with epilepsy, and 24 (29.3%, 24/82) with DD/ID with other structural anomalies. Among the 126 cases of pathogenic CNVs, 79 cases were identified as microdeletion/microduplication syndromes, among which 76 cases were classified as common syndromes, and 3 cases were classified as rare syndromes, including 15q24 microdeletion syndrome, Xq28 microduplication syndrome and Lowe syndrome. Additionally, there were forty-seven cases of non-syndromic pathogenic CNVs. The ABAT, FTSJ1, DYNC1H1, and SETBP1 genes were identified as DD/ID candidate genes. Conclusion: Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD/ID in South China. Key Words: developmental delay, intellectual disability, chromosome microarray analysis, CNVs, microdeletion/microduplication

Abstract Background Our study was aimed to explore the clinical implication of chromosome microarray analysis (CMA) in genetically etiological diagnosis of children with congenital heart disease (CHD). Methods A total of 104 children with CHD with or without multiple congenital anomalies (MCA) or intellectual disabilities/developmental delay (ID/DD) but normal karyotype were investigated using Affymetrix CytoScan HD array. Result Pathogenic copy number variations (PCNVs) were identified in 29 children (27.9%). The detection rates in children with simple CHD and complex CHD were 31.1% (19/61) and 23.2% (10/43), respectively. The detection rates of PCNVs were 17.9% (7/39), 20% (5/25), 63.2% (12/19) and 23.8% (5/21) in isolated CHD, CHD plus MCA, CHD plus ID/DD, CHD plus MCA and ID/DD, respectively. The PCNVs rate of CHD plus ID/DD was significantly higher than that of isolated CHD. Two genomic loci including 15q11.2 deletion and 1q43-q44 deletion were considered as CHD locus. The DVL1, SKI, STIM1, CTNNA3 and PLN were identified as candidate genes associated with CHD phenotypes. Conclusion CMA can increase the diagnostic rate and improve the etiological diagnosis in children with CHD. We suggest CMA as a first-tier test in children with CHD, especially in children with CHD plus ID/DD.

Objective: Smith–Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation disorder characterized by an interstitial deletion involving chromosome 17p11.2 containing the retinoic acid-induced 1 (RAI1) gene or due to mutation of RAI1. Few cases have been reported in the medical literature regarding prenatal diagnosis of SMS. We report on the prenatal diagnosis of SMS in two fetuses with increased nuchal translucency (NT), mild lateral ventriculomegaly, and congenital heart defects by whole-genome and high-resolution chromosome microarray analysis (CMA). Case Report: The CMA result of Fetus 1, which had increased NT, mild lateral ventriculomegaly, tricuspid regurgitation, and right aortic arch with left ductus arteriosus, revealed a de novo 4.79-Mb deletion at 17p12p11.2. Fetus 2 had increased NT, pulmonary stenosis, and a ventricular septal defect, and showed a de novo 3.68-Mb deletion at 17p11.2. Conclusion: The findings further confirm that increased NT is associated with genetic syndromes, and brain imaging is necessary for SMS fetuses. Both deletions encompass the SMS “critical region”, which includes many genes including RAI1. However, the precise gene(s) responsible for the heart defects in SMS remain unclear; further efforts should be undertaken to understand the molecular basis of this syndrome.

Current research on pedestrian flows has mainly focused on evacuation optimization during or after emergencies; however, crowd management before emergencies has received little attention. This paper examines the management of a Safe Pedestrian Flow Rate, in which the Bayesian-Nash Equilibrium mimics pedestrians’ decision-making, and a multiagent system is employed to reproduce pedestrians’ interactions. In the model, the pedestrian tunnel is divided into cells, with each pedestrian in a cell receiving a utility depending on the distance to the exit and the number of pedestrians in the cell. Then, each pedestrian uses the Bayesian-Nash Equilibrium to search for the target cell with maximum expected utility, moves in, and makes next decision until exiting the tunnel. The simulation model is calibrated and validated from a real scenario. Finally, from the experimental data collected from different simulation scenarios, this research reaches the conclusion that the Safe Pedestrian Flow Rate increases by about 2.96ped/s as the tunnel width expanded by 1m. This paper offers a novel method for reducing potential losses caused by crowd emergencies and can be a valuable reference for managing pedestrian flows and designing public places.

Objective: The objective of this study was to characterize the genetic abnormalities in two fetuses with congenital anomalies in prenatal screening. Materials and methods: The mother of Fetus 1 was 26 years old and had a second trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound and magnetic resonance imaging (MRI) at 28 weeks of gestation showed mild ventriculomegaly, microcephaly, and agenesis of the corpus callosum. The mother of Fetus 2 was 25 years old and also had a second trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 32 weeks of gestation showed the presence of hyperechogenic and enlarged kidneys with multicystic renal dysplasia bilaterally and a persistent left superior vena cava (PLSVC). Both pregnant women underwent cord blood samplings because of the abnormal imaging results. Karyotype analysis revealed normal results in the two fetuses. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the cord blood and parental blood samples. Ultimately, the pregnancies were both terminated. Results: CMA detected a 1.56-Mb duplication at 17q12 in Fetus 1 and a 1.93-Mb deletion of 17q12 in Fetus 2. Both the duplicated and deleted regions included the HNF1B and LHX1 genes. Neither the duplication nor deletion was inherited from the parents. Conclusion: This study is the first to report the prenatal diagnosis of a 17q12 duplication syndrome. Our results further confirmed that genes in this region, including HNF1B and LHX1, are essential for normal brain and kidney development, and also indicated some genes that may be associated with the cardiovascular abnormality. Combined with imaging examination, the use of CMA will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.

In this paper, we optimize the search and rescue (SAR) in disaster relief through agent-based simulation. We simulate rescue teams’ search behaviors with the improved Truncated Lévy walks. Then we propose a cooperative rescue plan based on a distributed auction mechanism, and illustrate it with the case of landslide disaster relief. The simulation is conducted in three scenarios, including “fatal”, “serious” and “normal”. Compared with the non-cooperative rescue plan, the proposed rescue plan in this paper would increase victims’ relative survival probability by 7–15%, increase the ratio of survivors getting rescued by 5.3–12.9%, and decrease the average elapsed time for one site getting rescued by 16.6–21.6%. The robustness analysis shows that search radius can affect the rescue efficiency significantly, while the scope of cooperation cannot. The sensitivity analysis shows that the two parameters, the time limit for completing rescue operations in one buried site and the maximum turning angle for next step, both have a great influence on rescue efficiency, and there exists optimal value for both of them in view of rescue efficiency.

As the "safety switch" of lithium batteries, the separator controls the electrochemical performance and safety performance of lithium batteries. However, highly flammable and easy to induce lithium dendrite generation of commercial polyolefin pose a huge safety hazard for current commercial lithium-ion batteries. Therefore, developing a flame-retardant, lithium dendrite-inhibiting separator can achieve further leap in the lithium battery industry. A "sandwich" separator (SPS-B) is designed by integrating silk fibroin (SF), decabromodiphenyl ethane, and polyvinyl alcohol through electrospinning. SPS-B shows excellent flame-retardant properties through a free radical trapping mechanism. Moreover, the SPS-B demonstrated satisfactory capability of suppressing lithium dendrites by constructing Li3N-SEI with high ionic conductivity and high strength, and the secondary structure β-sheets of SF can inhibit the "tip effect" of lithium dendrites, which enables efficient lithium plating/stripping in Li//Li and Li//Cu cells. In addition, the enhanced porosity, electrolyte affinity of SPS-B promotes excellent electrochemical performance with enhanced discharge capacity and reduced concentration polarization. Finally, fire risk of soft-pack batteries are evaluated by continuous external heating. Compared with commercial separator, soft-pack batteries with SPS-B show much lower heat release rate, peak temperature and flue gas release rate, further confirming the effectiveness of SPS-B in reducing fire risk. Overall, the SPS-B provides a satisfactory way to develop high-performance and superior safety lithium batteries. [ABSTRACT FROM AUTHOR]