| 21. |
- Liu, Lihui, et al.
(författare)
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Ablation of ERO1A induces lethal endoplasmic reticulum stress responses and immunogenic cell death to activate anti-tumor immunity
- 2023
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Ingår i: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.
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| 22. |
- Qian, Yan, et al.
(författare)
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Quantification for total demethylation potential of environmental samples utilizing the EGFP reporter gene
- 2016
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 306, s. 278-285
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The demethylation potential of pollutants is arguably an innate component of their toxicity in environmental samples. A method was developed for determining the total demethylation potential of food samples (TDQ). The demethylation epigenetic toxicity was determined using the Hep G2 cell line transfected with pEGFP-C3 plasmids containing a methylated promoter of the EGFP reporter gene. The total demethylation potential of the sample extracts (the 5-AZA-CdR demethylation toxic equivalency) can be quantified within one week by using a standard curve of the 5-AZA-CdR demethylation agent. To explore the applicability of TDQ for environmental samples, 17 groundwater samples were collected from heavy polluted Kuihe river and the total demethylation potentials of the sample extracts were measured successfully. Meaningful demethylation toxic equivalencies ranging from 0.00050 to 0.01747 μM were found in all groundwater sample extracts. Among 19 kinds of inorganic substance, As and Cd played important roles for individual contribution to the total demethylation epigenetic toxicity. The TDQ assay is reliable and fast for quantifying the DNA demethylation potential of environmental sample extracts, which may improve epigenetic toxicity evaluations for human risk assessment, and the consistent consuming of groundwater alongside the Kuihe river pose unexpected epigenetic health risk to the local residents.
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| 23. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 24. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 25. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 26. |
- Chen, Yaqi, et al.
(författare)
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Insight into the Extreme Side Reaction between LiNi0.5Co0.2Mn0.3O2 and Li1.3Al0.3Ti1.7(PO4)3 during Cosintering for All-Solid-State Batteries
- 2023
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Ingår i: Chemistry of Materials. - 1520-5002 .- 0897-4756. ; 35:22, s. 9647-9656
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Tidskriftsartikel (refereegranskat)abstract
- All-solid-sate batteries (ASSBs) with a NASICON-type solid-state electrolyte (SSE) of Li1.3Al0.3Ti1.7(PO4)3 (LATP) can be accepted as a promising candidate to significantly improve safety and energy density due to their high oxidation potential and high ionic conductivity. However, thermodynamic instability between the cathode and LATP is scarcely investigated during cosintering preparation for the integrated configuration of ASSBs. Herein, the structural compatibility between commercially layered LiNi0.5Co0.2Mn0.3O2 (NCM523) and LATP SSE was systematically investigated by cosintering at 600 °C. It is noticeable that an extreme side reaction between Li from NCM523 and phosphate from LATP happens during its cosintering process, leading to a severe phase transition from a layered to a spinel structure with high Li/Ni mixing. Consequently, the capacity of NCM523 is lost during the preparation of the NCM523-LATP composite cathode. Based on this, we suggested that the interface modification of the NCM523/LATP interface is valued significantly to inhibit this extreme side reaction, quickening the application of LATP-based ASSBs.
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| 27. |
- Cheng, Ye, et al.
(författare)
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Genetic variants in the HLA region contribute to the risk of cerebral palsy
- 2024
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Ingår i: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE. - 0925-4439 .- 1879-260X. ; 1870:3
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 x 10-14, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 x 10-4, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis.
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| 28. |
- Dong, Yu, et al.
(författare)
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Observation of a Ubiquitous (π, π)-Type Nematic Superconducting Order in the Whole Superconducting Dome of Ultra-Thin BaFe2–xNixAs2 Single Crystals
- 2021
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Ingår i: Chinese Physics Letters. - : Institute of Physics Publishing (IOPP). - 0256-307X .- 1741-3540. ; 38:9
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Tidskriftsartikel (refereegranskat)abstract
- In iron-based superconductors, the (0, pi) or (pi, 0) nematicity, which describes an electronic anisotropy with a four-fold symmetry breaking, is well established and believed to be important for understanding the superconducting mechanism. However, how exactly such a nematic order observed in the normal state can be related to the superconducting pairing is still elusive. Here, by performing angular-dependent in-plane magnetoresistivity using ultra-thin flakes in the steep superconducting transition region, we unveil a nematic superconducting order along the (pi, pi) direction in electron-doped BaFe2 - x Ni x As2 from under-doped to heavily overdoped regimes with x = 0.065-0.18. It shows superconducting gap maxima along the (pi, pi) direction rotated by 45 degrees from the nematicity along (0, pi) or (pi, 0) direction observed in the normal state. A similar (pi, pi)-type nematicity is also observed in the under-doped and optimally doped hole-type Ba1 - y K y Fe2As2, with y = 0.2-0.5. These results suggest that the (pi, pi) nematic superconducting order is a universal feature that needs to be taken into account in the superconducting pairing mechanism in iron-based superconductors.
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| 29. |
- Du, Jian, et al.
(författare)
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Antiproliferative effect of alpinetin in BxPC-3 pancreatic cancer cells
- 2012
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 29:4, s. 607-612
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Tidskriftsartikel (refereegranskat)abstract
- Alpinetin is a novel plant flavonoid derived from Alpinia katsumadai Hayata, found to possess strong anticancer effects. However, the antitumor effect of alpinetin on pancreatic cancer cells and the detailed mechanism remain unclear. The aim of this study was to investigate alpinetin's beneficial effect on pancreatic cancer and the possible molecular mechanism involved. Pancreatic cancer cell lines were treated with alpinetin at various doses and for different times, and the effect of alpinetin on cell growth inhibition, apoptosis and the cell cycle was determined. The expression of Bcl-2, Bcl-xL, XIAP and Bax, the activity of caspases and the levels of cytochrome c released were measured. The results showed that alpinetin inhibited the viability of three pancreatic cancer cell lines and induced apoptosis of BxPC-3 cells in a dose- and time-dependent manner. This was accompanied by regulation of the expression of Bcl-2, Bcl-xL, Bax and XIAP. Furthermore, alpinetin treatment led to the release of cytochrome c and activation of caspases-3, -8 and -9 proteins. Taken together, our studies indicate that alpinetin inhibited the proliferation of pancreatic cancer cells possibly through the regulation of the Bcl-2 family and XIAP expression, release of cytochrome c and the activation of caspases. Alpinetin may serve as a potential agent for the development of pancreatic cancer cell therapies.
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| 30. |
- Fan, Zheyong, et al.
(författare)
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GPUMD: A package for constructing accurate machine-learned potentials and performing highly efficient atomistic simulations
- 2022
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 1089-7690 .- 0021-9606. ; 157:11
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Tidskriftsartikel (refereegranskat)abstract
- We present our latest advancements of machine-learned potentials (MLPs) based on the neuroevolution potential (NEP) framework introduced in Fan et al. [Phys. Rev. B 104, 104309 (2021)] and their implementation in the open-source package gpumd. We increase the accuracy of NEP models both by improving the radial functions in the atomic-environment descriptor using a linear combination of Chebyshev basis functions and by extending the angular descriptor with some four-body and five-body contributions as in the atomic cluster expansion approach. We also detail our efficient implementation of the NEP approach in graphics processing units as well as our workflow for the construction of NEP models and demonstrate their application in large-scale atomistic simulations. By comparing to state-of-the-art MLPs, we show that the NEP approach not only achieves above-average accuracy but also is far more computationally efficient. These results demonstrate that the gpumd package is a promising tool for solving challenging problems requiring highly accurate, large-scale atomistic simulations. To enable the construction of MLPs using a minimal training set, we propose an active-learning scheme based on the latent space of a pre-trained NEP model. Finally, we introduce three separate Python packages, viz., gpyumd, calorine, and pynep, that enable the integration of gpumd into Python workflows.
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