The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2 virus) has been sustained in China since December 2019, and has become a ...pandemic. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the factors influencing medical worker anxiety in China during the COVID-19 outbreak. We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff in China from 10 February 2020 to 20 February 2020 using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, with the criteria of normal (⩽49), mild (50-59), moderate (60-70) and severe anxiety (⩾70). We used multivariable linear regression to determine the factors (e.g. having direct contact when treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status. Of 512 medical staff in China, 164 (32.03%) had had direct contact treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers suffering from moderate (1.36%) and four workers suffering from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients experienced higher anxiety scores than those who had not had direct contact (β value = 2.33, confidence interval (CI) 0.65-4.00; P = 0.0068). A similar trend was observed in medical staff from Hubei province, compared with those from other parts of China (β value = 3.67, CI 1.44-5.89; P = 0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (β value = 4.44, CI 1.55-7.33; P = 0.0028). In this survey of hospital medical workers during the COVID-19 outbreak in China, we found that study participants experienced anxiety symptoms, especially those who had direct clinical contact with infected patients; as did those in the worst affected areas, including Hubei province; and those who were suspect cases. Governments and healthcare authorities should proactively implement appropriate psychological intervention programmes, to prevent, alleviate or treat increased anxiety.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC ...intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Although 5-methylcytosine (m
C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the ...single-nucleotide resolution landscape of messenger RNA m
C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m
C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m
C 'reader' recognizing m
C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m
C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m
C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•The prevalence of anxiety and depression symptom was 7.7% and 12.2%, respectively.•Having confirmed and suspected cases in family members or relatives was associated with the higher risk of ...depression symptom.•Self-reported health condition was strongly associated with risk of anxiety and depression symptom.
: Although studies have suggested experiencing the epidemic of severe infectious diseases increased the prevalence of mental health problems, the association between COVID-19 epidemic and risk of anxiety and depression symptom in college students in China was unclear.
: A large cross-sectional online survey with 44,447 college students was conducted in Guangzhou, China. The Zung's Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D Scale) were used to define the anxiety and depression symptom, respectively. Multivariable logistic regression models were used to analyze the association between COVID-19 epidemic and risk of anxiety and depression symptom.
: The prevalence of anxiety and depression symptom was 7.7% (95% confidence interval CI: 7.5%, 8.0%) and 12.2% (95%CI: 11.9%, 12.5%), respectively. Compared with students who reported have not infected or suspected cases in family members and relatives, students who reported having confirmed (OR=4.06; 95%CI: 1.62, 10.19; P = 0.003), and suspected (OR=2.11; 95%CI: 1.11, 4.00; P = 0.023) cases in family members and relatives had higher risk of depression symptom. Additionally, the proportions of students with anxiety and depression symptom reported more demand of psychological knowledge and interventions than those without (P<0.001).
: All the data in this study was collected through online questionnaire, and we did not evaluate the reliability and validity.
: The prevalence of anxiety and depression symptom was relatively low in college students, but the COVID-19 epidemic-related factors might be associated with higher depression symptom risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The nucleocapsid (N) protein is an important antigen for coronavirus, which participate in RNA package and virus particle release. In this study, we expressed the N protein of SARS-CoV-2 and ...characterized its biochemical properties. Static light scattering, size exclusive chromatography, and small-angle X-ray scattering (SAXS) showed that the purified N protein is largely a dimer in solution. CD spectra showed that it has a high percentage of disordered region at room temperature while it was best structured at 55 °C, suggesting its structural dynamics. Fluorescence polarization assay showed it has non-specific nucleic acid binding capability, which raised a concern in using it as a diagnostic marker. Immunoblot assays confirmed the presence of IgA, IgM and IgG antibodies against N antigen in COVID-19 infection patients’ sera, proving the importance of this antigen in host immunity and diagnostics.
•SARS-CoV-2 nucleocapsid protein is full of coils and highly disordered.•SARS-CoV-2 N protein forms a dimer by CTD-CTD interaction.•SARS-CoV-2 N protein can bind with non-specific nucleic acid with high affinity.•SARS-CoV-2 N protein can be a good antigen for serological test of COVID-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic ...reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1’s cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.
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•RNA-BisSeq revealed a dynamic RNA m5C landscape during zebrafish embryogenesis•Ybx1 preferentially recognizes m5C-modified mRNAs•Ybx1 deficiency leads to early gastrulation defects in zebrafish embryos•Ybx1 and Pabpc1a coordinately regulate m5C-modified maternal mRNA stability
RNA modifications exert important effects in many critical physiological processes. Using RNA-BisSeq, Yang et al. provide a comprehensive view of the RNA m5C landscape in zebrafish early embryos and show that m5C-modified maternal mRNAs are stabilized by Ybx1 and Pabpc1a during zebrafish MZT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Microscale cell carriers have recently garnered enormous interest in repairing tissue defects by avoiding substantial open surgeries using implants for tissue regeneration. In this study, the highly ...open porous microspheres (HOPMs) are fabricated using a microfluidic technique for harboring proliferating skeletal myoblasts and evaluating their feasibility toward cell delivery application in situ. These biocompatible HOPMs with particle sizes of 280–370 µm possess open pores of 10–80 µm and interconnected paths. Such structure of the HOPMs conveniently provide a favorable microenvironment, where the cells are closely arranged in elongated shapes with the deposited extracellular matrix, facilitating cell adhesion and proliferation, as well as augmented myogenic differentiation. Furthermore, in vivo results in mice confirm improved cell retention and vascularization, as well as partial myoblast differentiation. These modular cell‐laden microcarriers potentially allow for in situ tissue construction after minimally invasive delivery providing a convenient means for regeneration medicine.
Highly open porous microspheres (HOPMs) are conveniently designed using a microfluidic setup and evaluated for their feasibility toward minimally invasive cell delivery‐based tissue regeneration. These biocompatible HOPMs with interconnected paths facilitate a high cell proliferation rate, and partial differentiation of skeletal myoblasts. These modular cells‐laden microcarriers provide a convenient means for in situ repair of tissue defects and applications in regenerative medicine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We combine the labeling of newly transcribed RNAs with 5-ethynyluridine with the characterization of bound proteins. This approach, named capture of the newly transcribed RNA interactome using click ...chemistry (RICK), systematically captures proteins bound to a wide range of RNAs, including nascent RNAs and traditionally neglected nonpolyadenylated RNAs. RICK has identified mitotic regulators amongst other novel RNA-binding proteins with preferential affinity for nonpolyadenylated RNAs, revealed a link between metabolic enzymes/factors and nascent RNAs, and expanded the known RNA-bound proteome of mouse embryonic stem cells. RICK will facilitate an in-depth interrogation of the total RNA-bound proteome in different cells and systems.
The methyltransferase like 3 （METTL3）-containing methyltransferase complex catalyzes the N6-methyladenosine （m6A） formation, a novel epitranscriptomic marker; however, the nature of this complex ...remains largely unknown. Here we report two new components of the human m6A methyltransferase complex, Wilms＇ tumor 1-associating protein （WTAP） and methyltransferase like 14 （METTL14）. WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic ac- tivity of the m6A methyltransferase in vivo. The majority of RNAs bound by WTAP and METTL3 in vivo represent mRNAs containing the consensus m6A motif. In the absence of WTAP, the RNA-binding capability of METTL3 is strongly reduced, suggesting that WTAP may function to regulate recruitment of the m6A methyltransferase complex to mRNA targets. Furthermore, transcriptomic analyses in combination with photoactivatable-ribonucleoside-en- hanced crosslinking and immunoprecipitation （PAR-CLIP） illustrate that WTAP and METTL3 regulate expression and alternative splicing of genes involved in transcription and RNA processing. Morpholino-mediated knockdown targeting WTAP and/or METTL3 in zebrafish embryos caused tissue differentiation defects and increased apoptosis. These findings provide strong evidence that WTAP may function as a regulatory subunit in the m6A methyltransferase complex and play a critical role in epitranscriptomic regulation of RNA metabolism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were ...more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.
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•We build the genomic and transcriptomic landscape of 465 primary TNBCs•Chinese TNBC cases demonstrate more PIK3CA mutations and LAR subtype•Transcriptomic data classify TNBCs into four subtypes•Multi-omics profiling identifies potential targets within specific TNBC subtypes
Jiang et al. characterize primary Chinese triple-negative breast cancer (TNBC) and classify it into four subtypes. They find that these TNBCs have more frequent PIK3CA mutations and chromosome 22q11 copy-number gains than non-Asian TNBCs and that the LAR subtype has more ERBB2 somatic mutations and CDKN2A loss.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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