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Objective: The purpose of this work was to obtain the phenotypes and detect potential mutations in three Chinese patients with Marfan syndrome (MFS) or incomplete MFS phenotypes. Methods: Three unrelated patients with a definite or suspected clinical diagnosis of MFS and their family members were recruited for research. Genomic DNA was extracted from peripheral blood of these patients and their family members. All the exons were sequenced by next-generation sequencing and the variants were further validated by Sanger sequencing. The functional consequences of the mutations were analyzed with various genomic resources and bioinformatics tools. Results: Three FBN1 mutations were identified in the three patients, including one novel mutation (2125G > A) and two previously reported mutations (4786C > T and 6325C > T). It was interesting to note that the parents of these patients were normal as assessed by clinical features or genetic testing, but all these mutations were detected in their offspring, except for the variant 6325C > T. We also found that a few young members of the family of probands (proband 1 and proband 2) have exhibited no manifestations of MFS so far, although they carry the same disease-causing mutation. Conclusions: We found three FBN1 mutations in three unrelated Chinese families with MFS by genome sequencing, and the relationship between genotypes and phenotypes in MFS patients needs further exploration.

Familial dilated cardiomyopathy (DCM) is associated with numerous genes, especially those of the sarcomere family. The titin gene (TTN) consists of 365 exons and encodes the largest sarcomere protein (titin) in our bodies. Titin is associated with many diseases, such as hypertrophic cardiomyopathy and DCM. Here we screened three Chinese families affected by DCM, and found that each harbors a stop-gain or splice site mutation in TTN (c.G20137T,c. G52522T,c.44610-2A>C). Assessment of the probands by electrocardiogram, B-mode echocardiography, and cardiac magnetic resonance imaging revealed impaired cardiac function, arrhythmia, or abnormal cardiac structure. In conclusion, using whole exome sequencing, we found three unreported TTN mutations associated with DCM. This has expanded the TTN mutation spectrum of Chinese DCM patients, especially in Henan, the most populous province. These data provide new genetic targets for the diagnosis and treatment of DCM, and will increase our understanding of the relationship between TTN mutation and DCM clinical symptoms.

Long QT syndrome (LQTS), which is caused by an ion channel–related gene mutation, is a malignant heart disease with a clinical course of a high incidence of ventricular fibrillation and sudden cardiac death in the young. Mutations in KCNH2 (which encodes potassium voltage-gated channel subfamily H member 2) are responsible for LQTS in many patients. Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing. The c.916dupA mutation in JUP (which encodes junction plakoglobin) is also discovered. Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy. The double mutation in the proband may help explain his severe clinical manifestations, such as sudden cardiac death at an early age. Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line, while the mutation in JUP came from his maternal line. The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.

ObjectiveLow-density lipoprotein receptor-related protein-1 (LRP-1) and survivin are associated with radiotherapy resistance in patients with locally advanced rectal cancer (LARC). This study aimed to evaluate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the preoperative assessment of LRP-1 and survivin expressions in these patients.MethodsOne hundred patients with pathologically confirmed LARC who underwent DCE-MRI before surgery between February 2017 and September 2021 were included in this retrospective study. DCE-MRI perfusion histogram parameters were calculated for the entire lesion using post-processing software (Omni Kinetics, G.E. Healthcare, China), with three quantitative parameter maps. LRP-1 and survivin expressions were assessed by immunohistochemical methods and patients were classified into low- and high-expression groups.ResultsFour radiomics features were selected to construct the LRP-1 discrimination model. The LRP-1 predictive model achieved excellent diagnostic performance, with areas under the receiver operating curve (AUCs) of 0.853 and 0.747 in the training and validation cohorts, respectively. The other four radiomics characteristics were screened to construct the survivin predictive model, with AUCs of 0.780 and 0.800 in the training and validation cohorts, respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics models.ConclusionDCE-MRI radiomics models are particularly useful for evaluating LRP-1 and survivin expressions in patients with LARC. Our model has significant potential for the preoperative identification of patients with radiotherapy resistance and can serve as an essential reference for treatment planning.

BACKGROUND: Alzheimer’s disease (AD) is closely related to immunity and competitive endogenous RNAs (ceRNAs) are believed to play a key role in the development of AD. Therefore, understanding the ceRNA network related to AD immunity will contribute to the identification of novel immunotherapeutic targets and provide new insights into AD from an immunological perspective. METHODS: Weighted gene coexpression network analysis (WGCNA) and Enrichr enrichment analysis were performed to identify the immune-related gene coexpression modules through microarray datasets from the Gene Expression Omnibus (GEO) database. The differentially expressed long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were identified from the microarray through differential analysis and mapped with related databases. Cytoscape was used to construct a lncRNA-miRNA-mRNA network. Subsequently, ImmuCellAI immune infiltration analysis was performed and a ceRNA sub-network of related core immune cells was constructed. Finally, the potential pathways related to these core factors were determined through gene set enrichment analysis (GSEA). RESULTS: Through WGCNA analysis and enrichment analysis, the blue module and the green module were identified as key modules related to AD immunity. Naïve CD8 cells were shown to be the key immune cells related to AD. Correlation analysis and receiver operating characteristic (ROC) curves verified lncRNA Long Intergenic Non-Protein Coding RNA 472 (LINC00472), lncRNA HLA Complex Group 18 (HCG18), RUNX Family Transcription Factor 3 (RUNX3), Tensionin 1 (TNS1), Linker For Activation Of T Cells Family Member 2 (LAT2), and Solute Carrier Family 38 Member 2 (SLC38A2) as possible key targets related to AD immunity. CONCLUSIONS: The lncRNA LINC00472, lncRNA HCG18, RUNX3, TNS1, LAT2, and SLC38A2 identified in this study may be key targets related to AD immunity. These insights will provide future directions for the further AD research.

This appendix of the book Liangyou: Kaleidoscopic Modernity and the Shanghai Global Metropolis, 1926-1945 presents distribution notes on Chinese magazine - Liangyou . The Liangyou ( The Young Companion ) pictorial commanded an impressive market at home in China and abroad in the 1920s. Its kaleidoscopic blast attracted readers at that time just as it attracts researchers today. There is no doubt that the management of Liangyou was a major commercial success story. Among all magazines in Republican Shanghai, sales of 35,000 to 40,000 copies would rank Liangyou second, one notch behind the top-selling Shenghuo zhoukan ( Life Weekly ). According to an accounting agency, Liangyou was at first distributed in three ways: wholesale transactions, subscriptions, as well as retail and mail order sales. Retail and mail order sales reached a total of 4556 copies according to data from the Shu Lun Pan accountants. This statistic underscores the prosperity of Liangyou Company. Keywords: China; Liangyou ; mail order sales; Republican Shanghai; Shenghuo zhoukan ; Shu Lun Pan accountants; subscriptions; wholesale transactions

Funder: Science and Technology Commission of Shanghai Municipality; FundRef: http://dx.doi.org/10.13039/501100003399, Funder: Dr. John T. MacDonald Foundation; FundRef: http://dx.doi.org/10.13039/100010239, Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration.