| 1. |
- Xie, Jiaying, et al.
(author)
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STING activation in TET2-mutated hematopoietic stem/progenitor cells contributes to the increased self-renewal and neoplastic transformation
- 2023
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In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 37:12, s. 2457-2467
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Journal article (peer-reviewed)abstract
- Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain unclear. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in dysregulated hematopoiesis in mouse models. DNA damage arising in Tet2-deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn promotes the enhanced self-renewal and development of CH. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant hematopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the development of CH associated with TET2 mutations is powered through chronic inflammation dependent on the activated cGAS-STING pathway and that STING may represent a potential target for intervention of relevant hematopoietic diseases.
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| 2. |
- Clarke, Andrew J., et al.
(author)
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Non-fullerene acceptor photostability and its impact on organic solar cell lifetime
- 2021
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In: Cell Reports Physical Science. - : Elsevier. - 2666-3864. ; 2:7
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Journal article (peer-reviewed)abstract
- The development of non-fullerene acceptors (NFAs) has facilitated the realization of efficient organic solar cells (OSCs) with minimal burn-in losses and excellent long-term stability. However, the role of NFA molecular structures on device stability remains unclear, limiting commercialization of NFA-based OSCs. Herein, the photostability of 10 OSC devices, fabricated with various NFAs (O-IDTBR, EH-IDTBR, ITIC, and ITIC-M) blended with donor polymers (PTB7-Th, PffBT4T-2OD, and PBDB-T), is investigated. O-IDTBR and EH-IDTBR form highly stable devices with all three polymers, whereas ITIC and ITIC-M devices suffer from burn-in losses and long-term degradation. Conformational instability is found to be responsible for the poor photostability of ITIC and ITIC-M, resulting in poor device stability. Twisting and potential breakage of the chemical bond that links the end group to the main backbone of ITIC and ITIC-M molecules causes undesirable conformational changes. Potential strategies to overcome such detrimental photo-induced conformational changes in NFAs are proposed.
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| 3. |
- Lai, Heidi T. M., et al.
(author)
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Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes : Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE)
- 2022
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:4, s. 854-863
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >= 18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P >= 0.1).CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.
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| 4. |
- Lin, Yen-Hung, et al.
(author)
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A piperidinium salt stabilizes efficient metal-halide perovskite solar cells
- 2020
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In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 369:6499, s. 96-
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Journal article (peer-reviewed)abstract
- Longevity has been a long-standing concern for hybrid perovskite photovoltaics. We demonstrate high-resilience positive-intrinsic-negative perovskite solar cells by incorporating a piperidinium-based ionic compound into the formamidinium-cesium lead-trihalide perovskite absorber. With the bandgap tuned to be well suited for perovskite-on-silicon tandem cells, this piperidinium additive enhances the open-circuit voltage and cell efficiency. This additive also retards compositional segregation into impurity phases and pinhole formation in the perovskite absorber layer during aggressive aging. Under full-spectrum simulated sunlight in ambient atmosphere, our unencapsulated and encapsulated cells retain 80 and 95% of their peak and post-burn-in efficiencies for 1010 and 1200 hours at 60 degrees and 85 degrees C, respectively. Our analysis reveals detailed degradation routes that contribute to the failure of aged cells.
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| 5. |
- Qian, Deping, et al.
(author)
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Correlating the Hybridization of Local-Exciton and Charge-Transfer States with Charge Generation in Organic Solar Cells
- 2023
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In: Advanced Energy Materials. - : WILEY-V C H VERLAG GMBH. - 1614-6832 .- 1614-6840. ; 13
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Journal article (peer-reviewed)abstract
- In organic solar cells with very small energetic-offset (& UDelta;ELE - CT), the charge-transfer (CT) and local-exciton (LE) states strongly interact via electronic hybridization and thermal population effects, suppressing the non-radiative recombination. Here, we investigated the impact of these effects on charge generation and recombination. In the blends of PTO2:C8IC and PTO2:Y6 with very small, ultra-fast CT state formation was observed, and assigned to direct photoexcitation resulting from strong hybridization of the LE and CT states (i.e., LE-CT intermixed states). These states in turn accelerate the recombination of both CT and charge separated (CS) states. Moreover, they can be significantly weakened by an external-electric field, which enhanced the yield of CT and CS states but attenuated the emission of the device. This study highlights that excessive LE-CT hybridization due to very low , whilst enabling direct and ultrafast charge transfer and increasing the proportion of radiative versus non-radiative recombination rates, comes at the expense of accelerating recombination losses competing with exciton-to-charge conversion process, resulting in a loss of photocurrent generation.
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