| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Guo, JP, et al.
(author)
-
Sequencing of the MHC region defines HLA-DQA1 as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population
- 2019
-
In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:6, s. 773-780
-
Journal article (peer-reviewed)abstract
- The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC.MethodsWe first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case–control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants.ResultsHLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10−36, OR=2.29). DRβ1:37N had an independent protective effect (p=5.81×10−16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRβ1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.ConclusionsWe provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Zhang, L, et al.
(author)
-
Using human genetics to understand the epidemiological association between obesity, serum urate, and gout
- 2023
-
In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3280-3290
-
Journal article (peer-reviewed)abstract
- ObjectivesWe aimed to clarify the genetic overlaps underlying obesity-related traits, serum urate, and gout.MethodsWe conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci, and causal relationships between obesity (the exposure variable), gout (the primary outcome) and serum urate (the secondary outcome). Summary statistics were collected from the hitherto largest genome-wide association studies conducted for BMI (N = 806 834), waist-to-hip ratio (WHR; N = 697 734), WHR adjusted for BMI (WHRadjBMI; N = 694 649), serum urate (N = 288 649), and gout (Ncases = 13 179 and Ncontrols = 750 634).ResultsPositive overall genetic correlations were observed for BMI (rg = 0.27, P = 6.62 × 10−7), WHR (rg = 0.22, P = 6.26 × 10−7) and WHRadjBMI (rg = 0.07, P = 6.08 × 10−3) with gout. Partitioning the whole genome into 1703 LD (linkage disequilibrium)-independent regions, a significant local signal at 4q22 was identified for BMI and gout. The global and local shared genetic basis was further strengthened by the multiple pleiotropic loci identified in the cross-phenotype association study, multiple shared gene–tissue pairs observed by Transcriptome-wide association studies, as well as causal relationships demonstrated by Mendelian randomization [BMI–gout: OR (odds ratio) = 1.66, 95% CI = 1.45, 1.88; WHR–gout: OR = 1.57, 95% CI = 1.37, 1.81]. Replacing the binary disease status of gout with its latent pathological measure, serum urate, a similar pattern of correlation, pleiotropy and causality was observed with even more pronounced magnitude and significance.ConclusionOur comprehensive genome-wide cross-trait analysis demonstrates a shared genetic basis and pleiotropic loci, as well as a causal relationship between obesity, serum urate, and gout, highlighting an intrinsic link underlying these complex traits.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Pelaz, B, et al.
(author)
-
Diverse Applications of Nanomedicine
- 2017
-
In: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 11:3, s. 2313-2381
-
Journal article (peer-reviewed)
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Zhu, RJ, et al.
(author)
-
Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
-
In: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
-
Journal article (peer-reviewed)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Callaway, EM, et al.
(author)
-
A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
|
|
| 39. |
- Chen, DS, et al.
(author)
-
Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
-
Journal article (peer-reviewed)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Dong, CH, et al.
(author)
-
PPFIBP1 induces glioma cell migration and invasion through FAK/Src/JNK signaling pathway
- 2021
-
In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:9, s. 827-
-
Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM) is the most aggressive brain tumor, with a 5-year survival ratio <5%. Invasive growth is a major determinant of the poor prognosis in GBM. In this study, we demonstrate that high expression of PPFIA binding protein 1 (PPFIBP1) correlates with remarkable invasion and poor prognosis of GBM patients. Using scratch and transwell assay, we find that the invasion and migration of GBM cells are promoted by overexpression of PPFIBP1, while inhibited by knockdown of PPFIBP1. Then, we illustrate that overexpression of PPFIBP1 facilitates glioma cell infiltration and reduces survival in xenograft models. Next, RNA-Seq and GO enrichment analysis reveal that PPFIBP1 regulates differentially expressed gene clusters involved in the Wnt and adhesion-related signaling pathways. Furthermore, we demonstrate that PPFIBP1 activates focal adhesion kinase (FAK), Src, c-Jun N-terminal kinase (JNK), and c-Jun, thereby enhancing Matrix metalloproteinase (MMP)-2 expression probably through interacting with SRCIN1 (p140Cap). Finally, inhibition of phosphorylation of Src and FAK significantly reversed the augmentation of invasion and migration caused by PPFIBP1 overexpression in GBM cells. In conclusion, these findings uncover a novel mechanism of glioma invasion and identify PPFIBP1 as a potential therapeutic target of glioma.
|
|
| 44. |
|
|
| 45. |
- Feng, HL, et al.
(author)
-
Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study
- 2023
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 930-
-
Journal article (peer-reviewed)abstract
- There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
