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Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome is an autosomal recessive genetic disorder caused by mutations in NHL-repeat-containing protein 2 (NHLRC2) gene. This case report describes two Chinese siblings with FINCA syndrome carrying a novel frameshift variant, c.1610dupT (p.L537Ffs*17), of NHLRC2 gene. They shared similar symptoms of interstitial lung disease (ILD) and neurodegeneration, with early onset during infancy, and shared similar chest CT findings of bilateral ground-glass opacities and consolidations. The elder brother died of infantile respiratory failure, while the younger brother showed improvement in respiratory symptoms, chest CT, and Krebs von den Lungen-6 levels after long-term systemic glucocorticoid therapy, indicating that anti-inflammatory treatment may be beneficial in the treatment of ILD caused by FINCA syndrome.

Abstract Civic scientific literacy (CSL) is a fundamental indicator of social development and national literacy and is very important for personal well-being and national competitiveness. To be in line with the technological advancements and demands of the current era, we focused on “science engagement”, which is now considered an important approach to enhance the CSL of the general public, and developed a 4-dimensional CSL assessment framework based on the crucial elements for citizens to engage in science. The 4 dimensions are scientific knowledge (SK), scientific method (SM), problem-solving (PS), and scientific thought and spirit of science (STSS). With this framework, a CSL measurement instrument including 50 items was developed. Various validity evidence, including evidence with reliability close to or exceeding 0.8 for all four dimensions, supports the use of the instrument to provide a valuation of CSL. Age, location type (urban or rural), educational background, and occupation are all significant factors associated with CSL.

BackgroundChronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR).MethodsThe research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software.ResultsThe IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: β = 0.015, 95% CI: 0.005–0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: β = 0.02, 95% CI: 0.010–0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO.ConclusionGenetic evidence indicates a positive correlation between CHF and pars opercularis TH.

ABSTRACT A deep understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–host interactions is crucial to developing effective therapeutics and addressing the threat of emerging coronaviruses. The role of noncoding regions of viral RNA (ncrRNAs) has yet to be systematically scrutinized. We developed a method using MS2 affinity purification coupled with liquid chromatography-mass spectrometry and designed a diverse set of bait ncrRNAs to systematically map the interactome of SARS-CoV-2 ncrRNA in Calu-3, Huh7, and HEK293T cells. Integration of the results defined the core ncrRNA–host protein interactomes among cell lines. The 5′ UTR interactome is enriched with proteins in the small nuclear ribonucleoproteins family and is a target for the regulation of viral replication and transcription. The 3′ UTR interactome is enriched with proteins involved in the stress granules and heterogeneous nuclear ribonucleoproteins family. Intriguingly, compared with the positive-sense ncrRNAs, the negative-sense ncrRNAs, especially the negative-sense of 3′ UTR, interacted with a large array of host proteins across all cell lines. These proteins are involved in the regulation of the viral production process, host cell apoptosis, and immune response. Taken together, our study depicts the comprehensive landscape of the SARS-CoV-2 ncrRNA–host protein interactome and unveils the potential regulatory role of the negative-sense ncrRNAs, providing a new perspective on virus–host interactions and the design of future therapeutics. Given the highly conserved nature of UTRs in positive-strand viruses, the regulatory role of negative-sense ncrRNAs should not be exclusive to SARS-CoV-2. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic affecting millions of lives. During replication and transcription, noncoding regions of the viral RNA (ncrRNAs) may play an important role in the virus–host interactions. Understanding which and how these ncrRNAs interact with host proteins is crucial for understanding the mechanism of SARS-CoV-2 pathogenesis. We developed the MS2 affinity purification coupled with liquid chromatography-mass spectrometry method and designed a diverse set of ncrRNAs to identify the SARS-CoV-2 ncrRNA interactome comprehensively in different cell lines and found that the 5′ UTR binds to proteins involved in U1 small nuclear ribonucleoprotein, while the 3′ UTR interacts with proteins involved in stress granules and the heterogeneous nuclear ribonucleoprotein family. Interestingly, negative-sense ncrRNAs showed interactions with a large number of diverse host proteins, indicating a crucial role in infection. The results demonstrate that ncrRNAs could serve diverse regulatory functions.

RFWD2, an E3 ubiquitin ligase, is overexpressed in numerous human cancers, including leukemia, lung cancer, breast cancer, renal cell carcinoma, and colorectal cancer. The roles of RFWD2 in cancer are related to the targeting of its substrates for ubiquitination and degradation. This study aimed to investigate the role of TRIB2 in relation to the regulation of protein degradation through RFWD2. inBio Discover™ results demonstrated that TRIB2 can perform its functions by interacting with RFWD2 or other factors. TRIB2 can interact with and regulate RFWD2, which further attends the proteasome-mediated degradation of the RFWD2 substrate p-IκB-α. TRIB2 colocalizes with RFWD2-related IκB-α to form a ternary complex and further affects the IκB-α degradation by regulating its phosphorylation. Specific domain analysis showed that TRIB2 may bind to RFWD2 via its C-terminus, whereas it binds to IκB via its pseudokinase domain. TRIB2 acts as an oncogene and promotes cancer cell proliferation and migration, whereas RFWD2 knockdown reversed the role of TRIB2 in promoting cancer cell growth and colony formation in vitro and in vivo. In summary, this study reveals that TRIB2 promotes the progression of cancer by affecting the proteasome-mediated degradation of proteins through the interaction with RFWD2.