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Background Preterm birth (PTB), complications of which account for approximately 35% of deaths among neonates, remains a crucial issue. Cervical insufficiency (CI) is defined as the inability of the utrine cervix to retain a pregnancy, leading to PTB. Cervical cerclage is an efficient surgery for CI patients by preventing the cervix from being further mechanically shortened. Unfortunately, a certain number of patients who had cerclage still delivered prematurely, raising the urgent need to accurately assess the risk of PTB in patients with cerclage. Uterine electromyography (uEMG) is an emerging technology that characterizes uterine contractions by describing the actual evolution process of uterine activity and has been used to predict PTB in recent years. Method In this single-center retrospective case-control study, singleton pregnancy women who received cervical cerclage and uEMG assessment between January 2018 and January 2022 at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. Results 32 PTBs were observed of the 69 women who underwent assessment. Based on multivariate logistic regression analysis, PTB after cerclage was significantly associated with previous PTB history or mid-trimester pregnancy loss (OR: 2.87, 95%CI: 1.49–5.54) and contraction frequency detected by uEMG (OR: 2.24, 95%CI: 1.44–3.49). The AUC of contraction frequency (0.766, P <0.001) was observed, and the optimal cut-off value suggested by Youden Index was 1.75 times per hour. Combined with previous preterm history and cervical length, the AUC of contraction frequency reached 0.858. After stratification by contraction frequency, the median duration was 11 weeks in the high frequency group (> 1.75 times per hour) and 15 weeks in the low frequency group (≤ 1.75 times per hour) ( P <0.001). Conclusions The uEMG effectively predicts PTB after transvaginal cervical cerclage and provides a new method for clinicians to evaluate the pregnancy outcome of CI patients.

This article proposes a new method for designing an optical transparent frequency-selective surface absorber using indium tin oxide (ITO) conductive film with different sheet resistances. This novel optical transparent frequency-selective absorber exhibits excellent optical transparency, ensuring a visible light transmittance exceeding 76%. Simultaneously, it exhibits broadband absorption characteristics covering the entire X-Ku band, with an absorption rate exceeding 90%. Due to the simplicity of the design, the overall structure is easily processable, and the desired product can be rapidly fabricated using laser etching equipment without adding any lumped elements in the design. Simulation and experimental results indicate that the S11–10 dB frequency range of the frequency-selective absorber is 7.7–18.4 GHz, with a transmission frequency range below −3 dB between 26.7–29.4 GHz. The findings suggest that this structure holds potential applications in microwave stealth design requiring optical transparency and high-throughput satellite communication scenarios.

ANKRD17 has recently been implicated in intellectual disability (ID) and autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. Using trio whole-exome sequencing (Trio-WES) and chromosomal microarray analysis (CMA), we identified two unrelated cases with novel de novo heterozygous ANKRD17 variants. Case 1 describes a fetus with multiple congenital anomalies, where genetic analysis revealed a microdeletion at 4q13.3 truncating the ANKRD17 gene. Case 2 involves a 12-year-old male presenting with mild ID and progressive social impairments, associated with a NM_032217.5: c.1252 C > T (p.Arg418*) variation in ANKRD17 . Our study highlighted in mouse models an association between Ankrd17 haploinsufficiency and deficits in social behavior, spatial learning and memory, as well as elevated anxiety. Furthermore, our studies suggest dysregulation of synaptic proteins and mitochondrial function, along with impaired neural circuits following Ankrd17 knockdown. These results expand the genetic and phenotypic spectrum of ANKRD17 -related disorders, underscore the critical role of mitochondrial dysfunction in the pathophysiology of ANKRD17 -related ID and ASD.

Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis. To investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA. We profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated . RP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients ( = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes ( and ) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis ( ( = 4.39E-08, Fold change = 4.17), ( = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1β, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA. Our results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA.

The essentiality of assembly assessment and assembly optimization in design stage is analyzed, and the existent problems of conventional assembly design method are illuminated. ADMDMU (Assembly Design Method based Digital Mock-Up) is illuminated, and the process of ADMDMU established, and the ADMDMU architecture is given out. The key techniques of ADMDMU are analyzed, and include assembly design based KBE (Knowledge Based Engineering) and virtual assembly based physically attribute. According to physical attribute, physically based modeling, visual object movement control, force simulation method and assembly sequence planning method are emphatically illuminated. Assembly design system based DMU is established in foundation of ADMDMU.

Wiring of cables is very important in the design of electro-mechanical products. Whereas, there is not an effectual virtual wiring method for the moment. Aimed at the problem, a virtual wiring is expatiated in this paper. Virtual layout design is achieved based on human-computer interaction, which is verified by virtual assembling. Geometrical modeling of cables, the precision of which is quite high, is established based on energy-optimized method. The characteristic of virtual assembling to the products, which make up of cables and other parts, is discussed. Especially, the assemble technique programming and transformation simulating of cables are studied. In the end, the wiring is actualized on a product, intention to validate the feasibility of the method.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex natural products with diverse bioactivities. Here we report discovery of a RiPP, kintamdin, for which the structure is determined through spectroscopy, spectrometry and genomic analysis to feature a bis -thioether macrocyclic ring and a β-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase homolog KinH and flavoprotein KinI, which share low homologues to enzymes known in other RiPP biosynthesis. During the posttranslational modifications, KinCD is responsible for the formation of the characteristic dehydroamino acid residues including the β-enamino acid residue, followed by oxidative decarboxylation on the C-terminal Cys and subsequent cyclization to provide the bis -thioether ring moiety mediated by coordinated action of KinH and KinI. Finally, conserved genomic investigation allows further identification of two kintamdin-like peptides among the kin -like BGCs, suggesting the occurrence of RiPPs from actinobacteria. The chemical diversity of peptides from ribosomal origin is a growing field of research. Here, the authors report the discovery, genomic and biosynthetic investigations of kintamdin, a ribosomally synthesized and post-translationally modified peptides featuring a beta-enamino acid and a bis-thioether macrocyclic motif.

Background Preeclampsia (PE) is a multisystem progressive disease that occurs during pregnancy. Previous studies have shown that the immune system is involved in the placental trophoblast function and the pathological process of uterine vascular remodeling in PE. However, its molecular mechanism is still unclear. This study aimed to identify critical genes and immune cells involved in the pathological process of PE. Methods The PE-related GSE74341 and GSE160888 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis were combined to screen the PE-related DEGs. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic specificity of obtained DEGs, and the GSE35574 dataset was used for preliminary validation. Furthermore, the single-sample Gene Set Enrichment Analysis (ssGSEA) was used to elucidate the correlation between the DEGs and the 28 types of infiltrating immune cells in PE. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to verify the differential expression of DEGs in the PE placental tissues. Results A total of 143 DEGs (DE-mRNAs) were screened using the PE datasets. The analysis of DEG modules and LASSO logistic regression were used to identify high-temperature requirement factor A4 (HtrA4), tumour suppressor candidate 3 (TUSC3), endothelial protein C receptor gene (PROCR), claudin 3 (CLDN3), and thioredoxin binding protein (TXNIP) as the hub DEGs in PE. Furthermore, validation with the GSE35574 dataset and ROC analysis was used to clarify that the HTRA4, PROCR, and TXNIP genes are potential markers of PE and are closely related to the infiltrating immune cells in PE, such as gamma delta T cells, mast cells, natural killer cells, and T follicular helper cells. Finally, differential HTRA4, PROCR, and TXNIP expression were confirmed in PE placental tissues ( p  < 0.001). Conclusion HTRA4, PROCR, and TXNIP can be used as potential PE biomarkers to provide a new strategy for early diagnosing and treating PE.

Psoriasis vulgaris (PV) is an inflammatory, chronically relapsing dermatological disease associated with significant comorbidities. Ixekizumab is recommended as the first-line therapy for severe PV, but encounters persistent challenges with relapse after treatment discontinuation. In clinical practice, Chinese herbal medicine (CHM) including Guben Qushi Huayu formula (GQHF) has been demonstrated effective in reducing PV relapse. However, there remains a scarcity of high-level evidence-based study in this respect. Therefore, this study aims to preliminarily evaluate the feasibility and acceptability of Ixekizumab combined with GQHF in reducing PV relapse. This study employs a mixed-method research (MMR) design, encompassing both quantitative and qualitative studies. The quantitative study consists of a randomized controlled trial involving 50 participants with severe PV, who will be randomly allocated to the intervention group (Ixekizumab plus GQHF) and the control group (Ixekizumab plus GQHF placebo) in a 1:1 ratio. Relapse rate is the primary endpoint. The qualitative study involves semi-structured interviews to concurrently explore the acceptability of the application of Ixekizumab combined with GQHF among the enrolled participants. This pilot study utilizes MMR to investigate the effect of Ixekizumab combined with GQHF in reducing PV relapse. The findings are expected to provide valuable clinical evidence and a novel therapeutic option for PV. Moreover, it is our intention to conduct a larger MMR trial to further strengthen the clinical evidence and broaden the application of Ixekizumab in combination with GQHF. https://www.chictr.org.cn/index.html, identifier ChiCTR2100054950.

Non-Ribosomal Peptide Synthetases (NRPSs) assemble a diverse range of natural products with important applications in both medicine and agriculture. They consist of several multienzyme subunits that must interact with each other in a highly controlled manner to facilitate efficient chain transfer, thus ensuring biosynthetic fidelity. Several mechanisms for chain transfer are known for NRPSs, promoting structural diversity. Herein, we report the first biochemically characterized example of a type II thioesterase (TE II ) domain capable of catalysing aminoacyl chain transfer between thiolation (T) domains on two separate NRPS subunits responsible for installation of a dehydrobutyrine moiety. Biochemical dissection of this process reveals the central role of the TE II -catalysed chain translocation event and expands the enzymatic scope of TE II domains beyond canonical (amino)acyl chain hydrolysis. The apparent co-evolution of the TE II domain with the NRPS subunits highlights a unique feature of this enzymatic cassette, which will undoubtedly find utility in biosynthetic engineering efforts. Non-Ribosomal Peptide Synthetases (NRPSs) are responsible for the construction of many types of natural products. Here the authors characterize a key type II thioesterase domain that sheds light on the chain translocation processes of legonmycin NRPSs.