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Abstract Background Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. Results We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. Conclusions These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.

The R2R3-MYB gene family represents a widely distributed class of plant transcription factors. This gene family plays an important role in many aspects of plant growth and development. However, the characterization of R2R3-MYB genes present in the genome of Coptis teeta has not been reported. Here, we describe the bioinformatic identification and characterization of 88 R2R3-MYB genes in this species, and the identification of members of the R2R3-MYB gene family in species within the order Ranales most closely related to Coptis teeta. The CteR2R3-MYB genes were shown to exhibit a higher degree of conservation compared to those of A. thaliana, as evidenced by phylogeny, conserved motifs, gene structure, and replication event analyses. Cis-acting element analysis confirmed the involvement of CteR2R3-MYB genes in a variety of developmental processes, including growth, cell differentiation, and reproduction mediated by hormone synthesis. In addition, through homology comparisons with the equivalent gene family in A. thaliana, protein regulatory network prediction and transcriptome data analysis of floral organs across three time periods of flower development, 17 candidate genes were shown to exhibit biased expression in two floral phenotypes of C. teeta. This suggests their potential involvement in floral development (anther development) in this species.

Epiverta chelonia (Mader 1933; Coleoptera: Coccinellidae) is an important economically and scientifically valuable insect. In this study, the first complete mitochondrial genome of E. chelonia was sequenced and characterized using next-generation sequencing techniques. The circular mitogenome of E. chelonia consists of 17,347 bp including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a control region (D-loop). The base composition was AT-biased (75.77%). Bayesian Inference and Maximum likelihood phylogenetic trees strongly supported the monophyly of Coccinellinae. Also, E. chelonia was supported as the sister group of Subcoccinella vigintiquatuorpunctata, within Epilachninae. Thus, the E. chelonia mitochondrial genome will be a fundamental resource for understanding the molecular phylogenetic relationships of the species-rich family Coccinellidae of Coleoptera.

With high real-time performance and a good filtering effect, the wavelet transform-based real-time filter is more commonly used in the fusion magnet power supply. Considering the signal characteristics of the fusion magnet power supply, the sliding time window method is widely used to satisfy the requirements of filtering efficiency. In this paper, an updated half-edge extension method is proposed to improve the boundary effect of sliding window data. Moreover, the hardware-based wavelet loopback structure is proposed to avoid the double computation of long sliding window data, thereby improving real-time performance and satisfying the demands of fusion magnet power supply filtering. The proposed half-edge extension method and the wavelet loopback structure are implemented by designed FPGA and experimented on the Experimental and Advanced Superconducting Tokamak (EAST) fusion magnet power supply system to verify the filtering efficiency. According to the experiment’s results, the proposed half-edge extension method has a better filtering effect, and the proposed wavelet loopback structure decreases the time by 67.4%, which can satisfy the requirements of the power supply system.

Gynostemma longipes contains an abundance of dammarane-type ginsenosides and gypenosides that exhibit extensive pharmacological activities. Increasing attention has been paid to the elucidation of cytochrome P450 monooxygenases (CYPs) and UDP-dependent glycosyltransferases (UGTs) that participate downstream of ginsenoside biosynthesis in the Panax genus. However, information on oxidosqualene cyclases (OSCs), the upstream genes responsible for the biosynthesis of different skeletons of ginsenoside and gypenosides, is rarely reported. Here, an integrative study of the metabolome and the transcriptome in the leaf, stolon, and rattan was conducted and the function of GlOSC1 was demonstrated. In total, 46 triterpenes were detected and found to be highly abundant in the stolon, whereas gene expression analysis indicated that the upstream OSC genes responsible for saponin skeleton biosynthesis were highly expressed in the leaf. These findings indicated that the saponin skeletons were mainly biosynthesized in the leaf by OSCs, and subsequently transferred to the stolon via CYPs and UGTs biosynthesis to form various ginsenoside and gypenosides. Additionally, a new dammarane-II synthase (DDS), GlOSC1, was identified by bioinformatics analysis, yeast expression assay, and enzyme assays. The results of the liquid chromatography–mass spectrometry (LC–MS) analysis proved that GlOSC1 could catalyze 2,3-oxidosqualene to form dammarenediol-II via cyclization. This work uncovered the biosynthetic mechanism of dammarenediol-II, an important starting substrate for ginsenoside and gypenosides biosynthesis, and may achieve the increased yield of valuable ginsenosides and gypenosides produced under excess substrate in a yeast cell factory through synthetic biology strategy.

With the growing complexity of integrated circuits (IC), more and more test patterns are added to test set to test more defects, making the number of test pattern and individual test pattern length continues to increase as the size of IC gets larger, boosting test time and consequently test cost. To solve this problem, this paper proposes a kind of valid pattern identification method. The method uses machine learning to reorder the test pattern which can select the most effective patterns, to determine the optimal training set and test set first. Then, by means of the weighted SVMRANK algorithm to find the optimal pattern sequence. Experiment results demonstrate that the method only sacrifices 2% prediction accuracy in exchange for 3.89 times the time saving. The method aims at maximizing the accuracy of test, and minimizing the number of patterns. The proposed idea significantly improves the test time and test efficiency compared to conventional test flows. This is an innovative test cost reduction method with the growing complexity of IC.

Security is critical to the growing popularity of the Internet of Things(IoT), and true random number generator (TRNG) plays an increasingly important role in information security systems. Conventional TRNGs use natural physical stochastic processes including thermal noise, chaos-based circuit, and so on to generate random numbers. These analog circuits based TRNG structures often consume excessive hardware resources. Meanwhile, it is difficult to incorporate them into digital system. In this paper, a novel all-digital true random number generator in SRAM-based FPGAs is proposed by using Vernier technique that precisely quantize random edge jitter. The proposed TRNG design is implemented on Xilinx Virtex-6 XC6VLX240T-1FF1156 FPGA and shows a high quality of randomness which has passed the NIST test suite with relatively high p-values, achieves a high throughput of 127 Mbps with occupying 32 slices. Experimental results show a good tolerance to bias phenomenon induced by process, voltage, and temperature variations.

Erigeron breviscapus (Vant.) Hand.-Mazz. is a famous traditional Chinese medicine that has positive effects on the treatment of cardiovascular and cerebrovascular diseases. With the increase of market demand (RMB 500 million per year) and the sharp decrease of wild resources, it is an urgent task to cultivate high-quality and high-yield varieties of E. breviscapus. However, it is difficult to obtain homozygous lines in breeding due to the self-incompatibility (SI) of E. breviscapus. Here, we first proved that E. breviscapus has sporophyte SI (SSI) characteristics. Characterization of the ARC1 gene in E. breviscapus showed that EbARC1 is a constitutive expression gene located in the nucleus. Overexpression of EbARC1 in Arabidopsis thaliana L. (Col-0) could cause transformation of transgenic lines from self-compatibility (SC) into SI. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated that EbARC1 and EbExo70A1 interact with each other in the nucleus, and the EbARC1-ubox domain and EbExo70A1-N are the key interaction regions, suggesting that EbARC1 may ubiquitinate EbExo70A to regulate SI response. This study of the SSI mechanism in E. breviscapus has laid the foundation for further understanding SSI in Asteraceae and breeding E. breviscapus varieties.

Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR), can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs.

Abstract This research aimed to assess the validity of ultrasound scans with new features in detecting fetal anal atresia and verify the effectiveness of these new features. Additionally, we aimed at investigating the perinatal incidence of anal atresia. This multicenter prospective study recruited 94,617 normal gravidas and 84 gravidas with anal atresia fetuses. The gold standard for diagnosing perinatal anal atresia is routine neonatal anus examinations. The incidence calculation was based on the results of the gold standard. The validity of our new approach was evaluated via a diagnostic test involving all 94,701 subjects. The effectiveness of our new features was assessed through an ablation study in a randomly established new dataset, with the ratio of anal atresia to non-anal atresia cases of 1:4. The annual perinatal incidence of anal atresia between 2019 and 2023 ranges from 0.57‰ to 1.29‰. Our new method performed great regarding the Youden index, diagnostic odds ratio (DOR), area under the curve (AUC) of the receiver operating characteristic curve (ROCC), AUC of the precision-recall curve (PRC), F1-score, and Cramer’s V. In the ablation study, our new approach surpassed its competitors concerning Youden index, DOR, AUC of the ROCC, and AUC of the PRC. Ultrasound scans show high validity and clinical value in detecting fetal anal atresia. Our new ultrasound features significantly promote the detection of fetal anal atresia.

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis and progression of autoimmune disease. Patients with rheumatoid arthritis (RA) are at high risk of developing atrial fibrillation (AF), while whether PCSK9 is involved in the onset of AF among RA patients remains unclear. Objectives: To explore the role of PCSK9 in the occurrence of AF in RA patients and decipher the underlying mechanism. Methods: We established a rat model of collagen-induced arthritis (CIA) by immunization with type II collagen in Freund’s incomplete adjuvant. Atrial electrophysiological test was used to evaluate AF susceptibility. We performed a clinical study to examine the correlation between PCSK9 level and AF, which recruited healthy control, RA patients and RA patients complicated with AF. Evolocumab (a monoclonal antibody of PCSK9) is administered via intraperitoneal injection in CIA rats to assess the role of PCSK9 in RA-related AF. LPS-RS (LPS inhibitor), clodronate liposomes (depletion of macrophages), and cell co-culture model were used to dissect the mechanism underlying PCSK9 promotes AF. Results: AF inducibility and duration were higher in CIA rats, accompanied by elevated plasma and atrial PCSK9. Interestingly, compared with healthy control subjects, patients with RA showed an increase in PCSK9, and the PCSK9 is much higher in RA patients complicated with AF. The level of PCSK9 was independently associated with AF risk in RA patients. In the in vivo experiment, evolocumab reduced AF susceptibility, and ameliorated atrial structural remodeling of CIA rats. Mechanistically, augmented LPS in CIA rats led to an increase in PCSK9, which exacerbated fibrosis of cardiac fibroblasts and apoptosis of cardiac myocytes by enhancement of M1 macrophages polarization and inflammation, thereby contributing to AF. Conclusion: This study suggests that elevated PCSK9 causes atrial structural remodeling by enhancement of M1 macrophages polarization in atria, and evolocumab can effectively protects CIA rats from AF.

Abstract This study aims at suggesting an end-to-end algorithm based on a U-net-optimized generative adversarial network to predict anterior neck lower jaw angles (ANLJA), which are employed to define fetal head posture (FHP) during nuchal translucency (NT) measurement. We prospectively collected 720 FHP images (half hyperextension and half normal posture) and regarded manual measurement as the gold standard. Seventy percent of the FHP images (half hyperextension and half normal posture) were used to fit models, and the rest to evaluate them in the hyperextension group, normal posture group (NPG), and total group. The root mean square error, explained variation, and mean absolute percentage error (MAPE) were utilized for the validity assessment; the two-sample t test, Mann–Whitney U test, Wilcoxon signed-rank test, Bland–Altman plot, and intraclass correlation coefficient (ICC) for the reliability evaluation. Our suggested algorithm outperformed all the competitors in all groups and indices regarding validity, except for the MAPE, where the Inception-v3 surpassed ours in the NPG. The two-sample t test and Mann–Whitney U test indicated no significant difference between the suggested method and the gold standard in group-level comparison. The Wilcoxon signed-rank test revealed significant differences between our new approach and the gold standard in personal-level comparison. All points in Bland–Altman plots fell between the upper and lower limits of agreement. The inter-ICCs of ultrasonographers, our proposed algorithm, and its opponents were graded good reliability, good or moderate reliability, and moderate or poor reliability, respectively. Our proposed approach surpasses the competition and is as reliable as manual measurement.

Research is presented describing the use of quantum mechanical calculations to explain an adduct, 5,6-azulyne trapped with furan, where a marked bond alternation is shown in the azulene pi system of the crystal structure.

Abstract Background Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. Case presentation A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks’ gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. Conclusion The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.