| 1. |
- Zhan, Lingling, et al.
(författare)
-
A Near-Infrared Photoactive Morphology Modifier Leads to Significant Current Improvement and Energy Loss Mitigation for Ternary Organic Solar Cells
- 2018
-
Ingår i: Advanced Science. - : WILEY. - 2198-3844. ; 5:8
-
Tidskriftsartikel (refereegranskat)abstract
- Herein, efficient organic solar cells (OSCs) are realized with the ternary blend of a medium band gap donor (poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo[1,2-b:4,5-b]dithiophene))-alt-(5,5-(1,3-di-2-thienyl-5,7-bis(2-ethylhexyl)benzo[1,2-c:4,5-c]dithiophene-4,8-dione)] (PBDB-T)) with a low band gap acceptor (2,2-((2Z,2Z)-(((2,5-difluoro-1,4-phenylene)bis(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b]dithiophene-6,2-diyl))bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (HF-PCIC)) and a near-infrared acceptor (2,2-((2Z,2Z)-(((4,4,9,9-tetrakis(4-hexylphenyl)-4,9-dihydro-s-indaceno[1,2-b:5,6-b]dithiophene-2,7-diyl)bis(4-((2-ethylhexyl)oxy)thiophene-5,2-diyl))bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (IEICO-4F)). It is shown that the introduction of IEICO-4F third component into PBDB-T:HF-PCIC blend increases the short-circuit current density (J(sc)) of the ternary OSC to 23.46 mA cm(-2), with a 44% increment over those of binary devices. The significant current improvement originates from the broadened absorption range and the active layer morphology optimization through the introduction of IEICO-4F component. Furthermore, the energy loss of the ternary cells (0.59 eV) is much decreased over that of the binary cells (0.80 eV) due to the reduction of both radiative recombination from the absorption below the band gap and nonradiative recombination upon the addition of IEICO-4F. Therefore, the power conversion efficiency increases dramatically from 8.82% for the binary cells to 11.20% for the ternary cells. This work provides good examples for simultaneously achieving both significant current enhancement and energy loss mitigation in OSCs, which would lead to the further construction of highly efficient ternary OSCs.
|
|
| 2. |
- Arora, Abishek, et al.
(författare)
-
Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics
- 2023
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors (lead, valproic acid, bisphenol A, ethanol, fluoxetine hydrochloride and zinc deficiency) and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after 5-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. Moreover, fluoxetine exposure elevated several fatty acids when validated using mass spectrometry-based metabolomics. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD.
|
|
| 3. |
- Gurol, Kerem C., et al.
(författare)
-
Manganese efflux transporter SLC30A10 missense polymorphism T95I associated with liver injury retains manganese efflux activity
- 2023
-
Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 324:1, s. 78-88
-
Tidskriftsartikel (refereegranskat)abstract
- The activity of the manganese (Mn) efflux transporter SLC30A10 in the liver and intestines is critical for Mn excretion and preventing Mn toxicity. Homozygous loss-of-function mutations in SLC30A10 are a well-established cause of hereditary Mn toxicity. But, the relationship between more common SLC30A10 polymorphisms, Mn homeostasis, and disease is only recently emerging. In 2021, the first coding SNP in SLC30A10 (T95I) was associated with liver disease raising the hypothesis that the T95I substitution may induce disease by inhibiting the Mn efflux function of SLC30A10. Here, we test this hypothesis using structural, viability, and metal quantification approaches. Analyses of a predicted structure of SLC30A10 revealed that the side chain of T95 pointed away from the putative Mn-binding cavity, raising doubts about the impact of the T95I substitution on SLC30A10 function. In HeLa or HepG2 cells, overexpression of SLC30A10-WT or T95I resulted in comparable reductions of intracellular Mn levels and protection against Mn-induced cell death. Furthermore, ΔSLC30A10 HepG2 cells, generated using CRISPR/Cas9, exhibited elevated Mn levels and heightened sensitivity to Mn-induced cell death, and these phenotypic changes were similarly rescued by expression of SLC30A10-WT or T95I. Finally, turnover rates of SLC30A10-WT or T95I were also comparable. In summary, our results indicate that the Mn transport activity of SLC30A10-T95I is essentially comparable to the WT protein. Our findings imply that SLC30A10-T95I either has a complex association with liver injury that extends beyond the simple reduction in SLC30A10 activity or alternatively the T95I mutation lacks a causal role in liver disease.NEW & NOTEWORTHY This study demonstrates that the T95I polymorphism in the manganese transporter SLC30A10, which has been associated with liver disease in human GWAS studies, does not impact transporter function in cell culture. These findings raise doubts about the causal relationship of the T95I polymorphism with human disease and highlight the importance of validating GWAS findings using mechanistic approaches.
|
|
| 4. |
- Han, Jing, et al.
(författare)
-
Altered expression of chondroitin sulfate structure modifying sulfotransferases in the articular cartilage from adult osteoarthritis and Kashin-Beck disease
- 2017
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 25:8, s. 1372-1375
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the expression of enzymes involved in chondroitin sulfate (CS) sulfation in the articular cartilage isolated from adult patients with osteoarthritis (OA) and Kashin-Beck disease (KBD), using normal adults as controls.METHODS: Articular cartilage samples were collected from normal, OA and KBD adults aged 38-60 years old, and divided into three groups with six individual subjects in each group. The morphology and pathology grading of knee joint cartilage was examined by Safranin O staining. The localization and expression of enzymes involved in CS sulfation (CHST-3, CHST-11, CHST-12, CHST-13, CHST-15, and UST) were examined by immunohistochemical staining and semi-quantitative analysis.RESULTS: Positive staining rates for anabolic enzymes CHST-3, CHST-12, CHST-15, and UST were lower in the KBD and OA groups than those in the control group. Meanwhile, reduced levels of CHST-11, and CHST-13 in KBD group were observed, in contrast to those in OA and control groups. The expressions of all six CS sulfation enzymes were less detected in the superficial and deep zones of KBD cartilage compared with control and OA cartilage.CONCLUSION: The reduced expression of the CS structure modifying sulfotransferases in the chondrocytes of both KBD and OA adult patients may provide explanations for their cartilage damages, and therapeutic targets for their treatment.
|
|
| 5. |
- Li, Danyang
(författare)
-
Genetic implications of individual intervention and neuronal dysfunction in neurodevelopmental disorders
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurodevelopmental disorders (NDDs) are a group of conditions appearing in childhood, with developmental deficits that produce impairments of functioning. Autism spectrum disorder (ASD) is a common NDD with a high heritability affected by complex genetic factors, including both common and rare variants. Behavior interventions such as social skills group training (SSGT) have been widely used in school-aged autistic individuals to relieve social communication difficulties in a group setting. Studies have confirmed that intervention outcomes can be influenced by sex and age, but how the genetic risk contributes to the outcome variability remains elusive. Furthermore, although large population cohorts have been well studied and have found numerous genes associated with ASD and NDDs, the molecular and neuronal outcomes of risk variants and genes are unclear. Therefore, this thesis included four studies in which the effects of genetic factors on intervention outcomes and cellular level neuronal functions were investigated. Results from this thesis may provide a genetic perspective for further studies to explore potential individualized treatments for ASD and other NDDs. Specifically, in STUDY 1-3, exome sequencing and microarray were performed on individuals from a randomized controlled trial of SSGT (KONTAKT®). Common and rare variants, including copy number variations (CNVs) and exome variants, were tested for association effects with SSGT and standard care intervention outcomes. Polygenic risk scores (PRSs) were calculated from common variants, and clinically significant rare CNVs and rare exome variants were prioritized. Molecular diagnoses were identified in 12.6% of the autistic participants. PRSs and carrier status of clinically significant rare variants were associated with intervention outcomes, although with varied effects on both SSGT and standard care. In addition, genetic scores representing variant loads in specific gene sets were obtained from rare and common variants in ASD-related pathways. Outcomes of interventions were differentially associated with genetic scores for ASD-related gene sets including synaptic transmission and transcription regulation from RNA polymerase II. After combining genetic information and behavior measures, a machine learning model was able to select important features and confirm that the intervention outcomes were predictable. In STUDY 4, genetic variants affecting Calcium/Calmodulin Dependent Serine Protein Kinase (CASK) gene, a risk gene for NDDs, were examined using human induced pluripotent stem cell-derived neuronal models to identify the cellular effects of these mutation consequences. CASK protein was reduced in maturing neurons from mutation carriers. Bulk RNA sequencing results revealed that the global expression of genes from presynaptic development and CASK network were downregulated in CASK-deficient neurons compared to controls. Neuronal cells influenced by CASK mutations showed a decrease of inhibitory presynapse size and changed excitatory-inhibitory (E/I) balance in developing neural circuitries. In summary, this is the first study to investigate the association of genome-wide rare and common variants with ASD intervention outcomes. Differential variant effects were found for individuals receiving SSGT or standard care. Future studies should include genetic information at different levels to improve molecular genetic testing for diagnoses and intervention plans. Presynapses and E/I imbalance could be an option to be developed for the treatment of CASK-related disorders.
|
|
| 6. |
- Li, Danyang, et al.
(författare)
-
Rare variants in the outcome of social skills group training for autism
- 2022
-
Ingår i: Autism Research. - : Wiley. - 1939-3792 .- 1939-3806. ; 15:3, s. 434-446
-
Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing has been proposed as the first-tier genetic testing in autism spectrum disorder (ASD). Here, we performed exome sequencing in autistic individuals with average to high intellectual abilities (N = 207) to identify molecular diagnoses and genetic modifiers of intervention outcomes of social skills group training (SSGT) or standard care. We prioritized variants of clinical significance (VCS), variants of uncertain significance (VUS) and generated a pilot scheme to calculate genetic scores of rare and common variants in ASD-related gene pathways. Mixed linear models were used to test the association between the carrier status of VCS/VUS or the genetic scores with intervention outcomes measured by the social responsiveness scale. Additionally, we combined behavioral and genetic features using a machine learning (ML) model to predict the individual response. We showed a rate of 4.4% and 11.3% of VCS and VUS in the cohort, respectively. Individuals with VCS or VUS had improved significantly less after standard care than non-carriers at post-intervention (β = 9.35; p = 0.036), while no such association was observed for SSGT (β = −2.50; p = 0.65). Higher rare variant genetic scores for synaptic transmission and regulation of transcription from RNA polymerase II were separately associated with less beneficial (β = 8.30, p = 0.0044) or more beneficial (β = −6.79, p = 0.014) effects after SSGT compared with standard care at follow-up, respectively. Our ML model showed the importance of rare variants for outcome prediction. Further studies are needed to understand genetic predisposition to intervention outcomes in ASD.
|
|
| 7. |
- Li, Danyang, et al.
(författare)
-
The effects of T-2 toxin on the prevalence and development of Kashin–Beck disease in China : a meta-analysis and systematic review
- 2016
-
Ingår i: Toxicology Research. - : Royal Society of Chemistry. - 2045-4538. ; 5:3, s. 731-751
-
Forskningsöversikt (refereegranskat)abstract
- To reveal the influence of T-2 toxin detection rate and detection amount in food samples on Kashin–Beck disease (KBD), and define a linking mechanism between T-2 toxin induced chondrocytes or cartilage damage and KBD pathological changes, seven electronic databases were searched to obtain epidemiological and experimental studies. For epidemiological studies, subgroup analyses of the positive detection rate (PDR) of the T-2 toxin and PDR of the T-2 toxin with concentrations (PDRC of T-2) >100 ng g−1 were carried out, together with a histogram of the T-2 toxin concentrations in different food types in KBD and non-KBD areas. For experimental studies, a systematic review of a variety of chondrocyte and cartilage changes and damage induced by the T-2 toxin was performed. As a result, in epidemiological studies, meta-analysis demonstrated that the T-2 toxin PDR and the overall PDRC of T-2 toxin >100 ng g−1 showed a slightly significant increase in KBD areas than that in non-KBD areas separately. From the histogram, T-2 toxin accumulation was more serious in endemic areas, especially in wheat flour samples. In experimental studies, the T-2 toxin could induce damage of chondrocytes and cartilage, and inhibit cell proliferation by promoting apoptosis and catabolism as well as intracellular injuries, which is similar to the characteristics of KBD. In conclusion, the amount of T-2 toxin detected has a more significant influence on KBD prevalence and development as compared to the T-2 toxin detection rate. Besides, the T-2 toxin induces chondrocyte and cartilage damage through apoptosis, catabolism promotion and intracellular impairment, which is similar to the KBD change.
|
|
| 8. |
- Li, Danyang, et al.
(författare)
-
The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder
- 2020
-
Ingår i: NPJ Genomic Medicine. - : Nature Publishing Group. - 2056-7944. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Social skills group training (SSGT) is a frequently used behavioral intervention in autism spectrum disorder (ASD), but the effects are moderate and heterogeneous. Here, we analyzed the effect of polygenic risk score (PRS) and common variants in gene sets on the intervention outcome. Participants from the largest randomized clinical trial of SSGT in ASD to date were selected (N = 188, 99 from SSGT, 89 from standard care) to calculate association between the outcomes in the SSGT trial and PRSs for ASD, attention-deficit hyperactivity disorder (ADHD), and educational attainment. In addition, specific gene sets were selected to evaluate their role on intervention outcomes. Among all participants in the trial, higher PRS for ADHD was associated with significant improvement in the outcome measure, the parental-rated Social Responsiveness Scale. The significant association was due to better outcomes in the standard care group for individuals with higher PRS for ADHD (post-intervention: β = −4.747, P = 0.0129; follow-up: β = −5.309, P = 0.0083). However, when contrasting the SSGT and standard care group, an inferior outcome in the SSGT group was associated with higher ADHD PRS at follow-up (β = 6.67, P = 0.016). Five gene sets within the synaptic category showed a nominal association with reduced response to interventions. We provide preliminary evidence that genetic liability calculated from common variants could influence the intervention outcomes. In the future, larger cohorts should be used to investigate how genetic contribution affects individual response to ASD interventions.
|
|
| 9. |
- Lin, Danyang, et al.
(författare)
-
A Si-containing FeCoCrNi high-entropy alloy with high strength and ductility synthesized in situ via selective laser melting
- 2020
-
Ingår i: Additive Manufacturing. - : Elsevier. - 2214-8604 .- 2214-7810. ; 35
-
Tidskriftsartikel (refereegranskat)abstract
- To widen the applications of new materials in additive manufacturing (AM), the traditional method of printing using pre-alloyed powders should be improved because the pre-alloying process is expensive and makes it difficult to adjust the composition of new materials. This study investigates the synthesis of a FeCoCrNi high-entropy alloy (HEA) containing 1.5 at.% Si in situ using selective laser melting (SLM). A remelting strategy and process optimization based on polynomial regression modeling allowed for the printing of almost fully dense (99.78 %) samples. The samples comprised columnar grains, each containing numerous subgrains of a single-phase face-centered cubic solid solution. No precipitation or segregation were observed. The room temperature tensile properties of the samples were excellent, with yields and tensile strengths reaching 701 +/- 14 and 907 +/- 25 MPa, respectively, and an elongation at fracture of 30.8 +/- 2%. These properties were attributed to solid solution strengthening and novel dislocation loop strengthening mechanism. These findings demonstrate that HEAs with a high relative density and good mechanical properties can be directly synthesized by SLM using inexpensive pure metal powders, thereby extending the application potential of AM to manufacture new materials.
|
|
| 10. |
- Mastropasqua, Francesca, et al.
(författare)
-
Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis.
- 2023
-
Ingår i: Biology open. - : The Company of Biologists. - 2046-6390. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants affecting Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU) have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role of HNRNPU in cerebral cortical development, but the effects of HNRNPU deficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes of HNRNPU locus deficiency during in vitro neural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate that HNRNPU deficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level HNRNPU downregulation leads to an increased fraction of neural progenitors in the maturing neuronal population. We conclude that the HNRNPU locus is involved in delayed commitment of neural progenitors to differentiate in cell types with hindbrain profile.
|
|
