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Introduction: The aim of this study was to investigate the presence of aortic isthmus flow reversal and its associated factors in fetuses with positive and false‐positive coarctation of the aorta (CoA) compared with normal controls. Material and Methods: Pregnant women with fetuses suspected of CoA and normal control were enrolled, and these women experienced prenatal ultrasound scan and followed up for 6 months after birth to confirm the presence of CoA. All the ultrasound parameters were analyzed. Results: A total of 134 pregnant women were enrolled, with 43 CoA‐positive fetuses and 91 CoA false‐positive fetuses, and 334 matched pregnant women were enrolled in the control group. Aortic isthmus flow reversal occurred in 28 (65.1%) fetuses in the CoA‐positive group, significantly (p < 0.05) more than in the false‐positive (37 or 40.7%) or control group (64 or 19.2%). Aortic isthmus flow reversal was mostly in the full systole (n = 17 or 60.7%) or late systole and early‐middle diastole (n = 10 or 35.7%) in the CoA‐positive fetuses (n = 27 or 96.4%), significantly (p < 0.001) different from that in the false‐positive or control group. The aortic isthmus flow reversal peak systolic velocity (PSV), flow volume, and ratio of reversed flow/forward flow were significantly (p < 0.05) increased in the CoA‐positive and false‐positive groups than in the control group. The aortic isthmus flow reversal incidence was significantly (p < 0.05) correlated with the middle cerebral artery (MCA) PSV in the total three groups or in the false‐positive group but was significantly (p < 0001) negatively correlated with the MCA resistance index (RI) in the CoA‐positive group. The incidence of the aortic isthmus flow reversal was significantly (p < 0.05) positively correlated with the umbilical artery (UA) RI in the false‐positive group and with the UA RI in the total three groups. Independently associated factors for aortic isthmus flow reversal were isthmic flow volume/CCO (combined cardiac output) in the CoA‐positive group. Conclusions: Reversal of flow in the aortic isthmus is much more common in true‐positive cases of CoA as compared to controls, and isthmic flow reversal in the full systolic phase only suggests presence of CoA. The aortic isthmic reversed flow volume accounts for over half of the isthmic forward flow volume in the CoA‐positive fetuses than in the normal controls. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is a nuclear cytoplasmic large DNA virus (NCLDV) that causes devastating hemorrhagic diseases in domestic pigs and wild boars, seriously threatening the development of the global pig industry. IFN-I plays an important role in the body's antiviral response. Similar to other DNA viruses, ASFV has evolved a variety of immune escape strategies to antagonize IFN-I signaling and maintain its proliferation. In this study, we showed that the ASFV early protein pK205R strongly inhibited interferon-stimulated genes (ISGs) as well as the promoter activity of IFN-stimulated regulatory elements (ISREs). Mechanistically, pK205R interacted with the intracellular domains of IFNAR1 and IFNAR2, thereby inhibiting the interaction of IFNAR1/2 with JAK1 and TYK2 and hindering the phosphorylation and nuclear translocation of STATs. Subsequently, we generated a recombinant strain of the ASFV-pK205R point mutation, ASFV-pK205R7PM. Notably, we detected higher levels of ISGs in porcine alveolar macrophages (PAMs) than in the parental strain during the early stages of ASFV-pK205R7PM infection. Moreover, ASFV-pK205R7PM attenuated the inhibitory effect on IFN-I signaling. In conclusion, we identified a new ASFV immunosuppressive protein that increases our understanding of ASFV immune escape mechanisms. Author summary: African Swine fever virus (ASFV) causes a deadly swine disease that originated in Africa and has since spread to Europe, Asia, and Oceania, severely impacting the global pig industry. Although ASFV protein functions have been extensively studied, many remain unknown. pK205R is abundantly expressed during the early stages of ASFV infection and participates in viral replication during the late stages of infection. Our research reveals how pK205R inhibits IFN-I signaling by interacting with IFNAR1 and IFNAR2, blocking downstream signaling. These results improve our understanding of the immune escape process of ASFV, which may have implications for future vaccine development. [ABSTRACT FROM AUTHOR]

To investigate the protective role of immune response gene 1 (IRG1) and exogenous itaconate in autoimmune hepatitis (AIH) and elucidate the underlying mechanisms. Wild-type and IRG1−/− AIH mouse models were established, and samples of liver tissue and ocular blood were collected from each group of mice to assess the effects of IRG1/itaconate on the expression of pro- and anti-inflammatory cytokines. The levels of liver enzymes and related inflammatory factors were determined using enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR). Liver histomorphology was detected through hematoxylin and eosin staining and then scored for liver injury, and the infiltration levels of tissue-resident memory T (TRM) cells and related molecules in the liver tissue were detected through immunofluorescence staining in vitro. RNA sequencing and gene enrichment analysis were conducted to identify the corresponding molecules and pathways, and lentiviral transfection was used to generate TRM cell lines with IRG1, Jak3, Stat3, and p53 knockdown. Real-time quantitative PCR and western blot were performed to detect the expression levels of relevant mRNAs and proteins in the liver tissue and cells. The percentage of apoptotic cells was determined using flow cytometry. IRG1/itaconate effectively reduced the release of pro-inflammatory cytokines and the pathological damage to liver tissue, thereby maintaining normal liver function. At the same time, IRG1/itaconate inhibited the JAK3/STAT3 signaling pathway, regulated the expression of related downstream proteins, and inhibited the proliferation and promoted the apoptosis of CD69+CD103+CD8+ TRM cells. For the first time, P53 was found to act as a downstream molecule of the JAK3/STAT3 pathway and was regulated by IRG1/itaconate to promote the apoptosis of CD8+ TRM cells. IRG1/itaconate can alleviate concanavalin A-induced autoimmune hepatitis in mice by inhibiting the proliferation and promoting the apoptosis of CD69+CD103+CD8+ TRM cells via the JAK3/STAT3/P53 pathway. [ABSTRACT FROM AUTHOR]

Objective: To define a novel classification of first branchial cleft anomalies (FBCAs) based on the relationship between lesions and the facial nerve in terms of radiographic imaging findings and to introduce the corresponding surgical managements. Methods: The clinical data were retrospectively reviewed. Novel classification was proposed according to the head–neck MRI findings and surgical records. FBCAs limited in the cartilaginous segment of external auditory canal (EAC) or superficial parotid gland capsule were classified as type A. Lesions close to the FN and(or) involved into the parotid gland with no scar formation and no previous parotidectomy were classified as type B. FBCAs adhered to the FN and(or) invaded the parotid gland with scar formation due to previous surgery were classified as type C. Appropriate surgery approaches was also described, which was correlated with classification. Results: Fifty‐one patients were included, and one patient suffered from bilateral lesions. Thirty‐one, twelve, and nine lesions were classified as type A, type B, and type C FBCAs, respectively. One type A patient (1.92%) suffered from recurrence during follow‐up. Temporary facial palsy (House‐Brackmann II) was identified in 2 type C patients (3.85%) after surgery and recovered to normal within 2 months. One type B patient (1.92%) suffered from facial paralysis due to the FN injury and underwent facial nerve graft simultaneously. No patients with type C complained of hearing loss postoperatively. Conclusion: This novel classification clearly illustrates definitely relationship between lesion and the facial nerve and appropriate surgical strategies were proposed based on the novel classification. Level of Evidence: 4 Laryngoscope, 134:4246–4251, 2024 [ABSTRACT FROM AUTHOR]

DO-178C as an acceptable compliance standard for airborne software airworthiness,it is clearly required that the software quality assurance(SQA)process must be included in the airborne software integration process.Based on the software life cycle definition,process and data of airborne software,the implementation of the software quality assurance process is analyzed from three aspects of objectives,activities,and compliance review based on DO-178C. In combination with software project quality management techniques and tools,the DO-178C-based software quality management method is studied from the three processes of software quality management planning,software quality management and software quality control,and some practical engineering suggestions are given.The results show that,by combining software quality assurance and quality management,the evidence of airworthiness requirements are generated,the civilian airborne software meeting the requirements is provided,and the quality and continuous improvement measurement are effectively ensured.

Abstract Background Primary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features. Methods Seventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants. Results Among the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2–21.3) and five novel variants, including 2 in the NR0B1 gene (c.323–324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein. Conclusions We found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.