| 1. |
- Wang, Sainan, et al.
(författare)
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Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment
- 2024
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Ingår i: International Journal of Infectious Diseases. - : ELSEVIER SCI LTD. - 1201-9712 .- 1878-3511. ; 140, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR -TB) treatment, as well as to identify predictive drug exposure thresholds. Methods: We conducted a prospective, observational multicenter study among participants receiving standardized MDR -TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration -time curve from 0 to 24 h, AUC0-24 h ) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. Results: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF > 450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART -derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg <middle dot>h/l (bedaquiline M2); 49.3 mg <middle dot>h/l (moxifloxacin); 119.3 mg <middle dot>h/l (linezolid); 718.7 mg <middle dot>h/l (cycloserine). Conclusions: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR -TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.
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| 2. |
- Zhou, Zichun, et al.
(författare)
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Subtle Molecular Tailoring Induces Significant Morphology Optimization Enabling over 16% Efficiency Organic Solar Cells with Efficient Charge Generation
- 2020
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Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- Manipulating charge generation in a broad spectral region has proved to be crucial for nonfullerene-electron-acceptor-based organic solar cells (OSCs). 16.64% high efficiency binary OSCs are achieved through the use of a novel electron acceptor AQx-2 with quinoxaline-containing fused core and PBDB-TF as donor. The significant increase in photovoltaic performance of AQx-2 based devices is obtained merely by a subtle tailoring in molecular structure of its analogue AQx-1. Combining the detailed morphology and transient absorption spectroscopy analyses, a good structure-morphology-property relationship is established. The stronger pi-pi interaction results in efficient electron hopping and balanced electron and hole mobilities attributed to good charge transport. Moreover, the reduced phase separation morphology of AQx-2-based bulk heterojunction blend boosts hole transfer and suppresses geminate recombination. Such success in molecule design and precise morphology optimization may lead to next-generation high-performance OSCs.
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| 3. |
- Zhu, Wanying, et al.
(författare)
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Dysfunction of vesicular storage in young-onset Parkinson's patient-derived dopaminergic neurons and organoids revealed by single cell electrochemical cytometry
- 2022
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Ingår i: Chemical Science. - 2041-6520. ; 13:21, s. 6217-6223
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical cytometry based on nano-tip microelectrodes was used to quantify the vesicular storage at the single-cell level in human neurons and midbrain organoids which acted as disease models of young-onset Parkinson's disease (YOPD). Human dopaminergic (DA) neurons and midbrain organoids were derived from an induced pluripotent stem cell line from one YOPD patient. We show a significant deficiency in vesicular catecholamine storage and a slower pore forming process on the surface of the microelectrode in the DA neurons derived from the YOPD patient. The upregulation of α-synuclein in both neurons and organoids derived from the YOPD patient is associated with vesicular storage dysfunction, revealing a correlation between the pathogenesis of YOPD and vesicular chemical storage deficiency, a novel chemical insight into the potential pathology of YOPD. Notably, efficacy evaluation and drug testing were performed with our platform to demonstrate that both amantadine, a clinical drug for Parkinson's disease (PD), and phorbol 12-myristate 13-acetate, an attractive candidate, ameliorate the dysfunction of vesicular storage in DA neurons derived from the YOPD patient. Our platform offers promising avenues for new drug discovery for PD and other neurodegenerative disorders.
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| 4. |
- Chen, Jingjing, et al.
(författare)
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Slippage on Porous Spherical Superhydrophobic Surface Revolutionizes Heat Transfer of Non-Newtonian Fluid
- 2022
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Ingår i: Advanced Materials Interfaces. - : John Wiley & Sons. - 2196-7350. ; 9:34
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a new strategy to achieve high-efficient heat transfer for non-Newtonian fluids with slippage using a stably prepared superhydrophobic coating is presented. A superhydrophobic coating is prepared on the inner surface of a sleeve at specific shear stress. The slippage and heat-transfer processes of the typical non-Newtonian fluid–1% carboxymethyl cellulose solutions on the superhydrophobic coating are investigated simultaneously. A novel porous spherical type of superhydrophobic coating with a contact angle of 168° is obtained. It is found that the shear stress in electrodeposition is a key parameter to control the morphology and wetting ability of the superhydrophobic coating. The slip length and enhancement factor of heat transfer for the non-Newtonian fluid on the coating are found in a range of 20–900 µm and 1.47 experimentally. A new parameter is proposed as Reynolds number Re divided by the dimensionless slip length ls* (Re/ls*) for the heat-transfer enhancement with slippage, which can be used as the guide for designing coating and selecting the operating conditions. The Re/ls* is <4, which can enhance the heat transfer via the slippage.
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| 5. |
- Chen, Lujie, et al.
(författare)
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Supply chain collaboration for sustainability: A literature review and future research agenda
- 2017
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Ingår i: International Journal of Production Economics. - : ELSEVIER SCIENCE BV. - 0925-5273 .- 1873-7579. ; 194, s. 73-87
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Forskningsöversikt (refereegranskat)abstract
- New technology is altering business strategies and innovation capabilities while increasing the possibilities of production and process innovation. Supply chain collaboration undertaken for the sake of sustainability is currently speeding up this process of change; a growing pool of research is exploring the links between sustainability collaboration and company performance on economic, environmental, and social metrics. It is a good time to review the literature to reveal what has been studied and what are the gaps in the current body of knowledge, and also to comment on what the future research agenda should include. For these purposes, the authors conducted a systematic literature review and a quantitative bibliometric analysis. Results indicate that research about supply chain collaboration for the purpose of sustainability is gaining growing attention in the business field; however, environmental and economic considerations still dominate the research, while there is a lack of consideration about social concerns such as child labor and personal development. In addition, the collaboration partners under investigation have mainly been the company and its customers and suppliers, whereas competitors and other horizontal collaboration partners have received little attention.
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| 6. |
- Deng, Bin, et al.
(författare)
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Ketamine inhibits TNF-α-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS
- 2022
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Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Systemic inflammatory response syndrome (SIRS) is a sepsis-associated inflammatory state and a self-defense mechanism against specific and nonspecific stimuli. Ketamine influences many key processes that are altered during sepsis. However, the underlying mechanisms remain incompletely understood. In this study, TNF-α-treated mice, as well as HT-29 and L929 cell models, were applied to characterize TNF-α-induced systemic and local cecal tissue inflammatory responses. Behavioral, biochemical, histological, and molecular biological approaches were applied to illustrate the related processes. Mice with TNF-α-induced SIRS showed systemic and local cecal tissue inflammatory responses, as indicated by increased levels of high mobility group box 1 protein (HMGB1), chemokines (C-X-C motif) ligand 10 (CXCL10), interleukin-6 (IL-6), and IL-10, as well as high mortality. Ketamine pretreatment alleviated death rates, symptoms, and the production of inflammatory cytokines induced by TNF-α in mice. Moreover, ketamine also protected the mice from TNF-α-induced cecal damage by suppressing the phosphorylation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). In addition, our results showed that ketamine efficiently inhibited TNF-α-induced necroptosis in HT-29 and L929 cells. Furthermore, we explored the mechanism using different L929 cell lines. The results displayed that ketamine inhibited TNF-α-induced necroptosis by enhancing RIP1 ubiquitination and reducing the RIP1-RIP3 and RIP3-MLKL interactions, as well as the formation of necrosomes. Thus, our study may provide a new theoretical and experimental basis for treating diseases characterized by SIRS-associated inflammatory factor storms. Moreover, our exploration may provide potential molecular mechanisms and targets for therapeutic intervention and clinical application of ketamine.
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| 7. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 8. |
- Gao, Qingwei, et al.
(författare)
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Preliminary study on mechanism of confined mass transfer and separation : "secondary confinement" effect of interfacial adsorption layer [限域传质分离机制初探:界面吸附层的"二次限域"效应]
- 2020
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Ingår i: Huagong Xuebao/CIESC Journal. - : Materials China. - 0438-1157. ; 71:10, s. 4688-4695
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Tidskriftsartikel (refereegranskat)abstract
- The confined mass transfer separation membrane is mainly for the high-precision separation process at the molecular/ion level, which is of great significance to solve the application needs of CO2 separation, azeotrope separation, lithium extraction from salt lake, desalination of seawater and so on. However, at present, the research of the confined mass transfer mechanism of this kind of membrane is lagging behind, and the theoretical models of confined mass transfer are lacking, which can no longer meet the needs of the rapid development of materials and chemical engineering. From the perspective of meso-science, the abnormal phenomenon of high flux and high selectivity of the confined mass transfer separation membrane is considered, that is, breaking through the trade-off effect, which is governed by compromise-in-competition between the selectivity mechanism and the flux mechanism. It is found that the fluid molecules will preferentially adsorb at the interface and form a stable adsorption layer. Based on this, the hypothesis of "secondary confinement" is put forward, that is, the surface induced new solid-like interface will have confinement effect on the intermediate fluid again. By comparing the pore size and the secondary confined size of the confined mass transfer separation membrane, the selective mechanism of the secondary confinement is further confirmed, and the quantitative prediction of the membrane flux and selectivity is preliminarily explored by combining the selective mechanism and the flux model, which may provide a theoretical basis for the precise construction of the limited area mass transfer membrane. © 2020, Chemical Industry Press Co., Ltd. All right reserved.
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| 9. |
- Liu, Feng, et al.
(författare)
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Modulating Structure Ordering via Side-Chain Engineering of Thieno[3,4-b]thiophene-Based Electron Acceptors for Efficient Organic Solar Cells with Reduced Energy Losses
- 2019
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Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 11:38, s. 35193-35200
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Tidskriftsartikel (refereegranskat)abstract
- Nonfullerene-based organic solar cells (OSCs) have made a huge breakthrough in the recent years. Introducing a proper side chain on the pi-conjugated backbone plays a vital role for further improving the power conversion efficiency (PCE) of OSCs due to easy tuning of the physical properties of the molecule such as absorption, energetic level, solid-state stacking, and charge transportation. More importantly, the side chain significantly affected the blend films morphology and thus determined the PCEs of the devices. In this work, two low-band-gap nonfullerene acceptors, ATT-4 and ATT-5, with an alkyl or branched alkyl substitute on indacenodithiophene (IDT) and thieno[3,4-b]thiophene (TbT) backbone were synthesized for investigating the effect of the substituent on the performance of the nonfullerene acceptors (NFAs). In comparison to ATT-1 with p-hexylphenyl-substituted IDT and n-octyl-substituted TbT moieties, ATT-4 and ATT-5 exhibit better crystallinity with shorter interchain distance and ordered molecular structure in neat and the corresponding blend films. The tailored ATT-5 exhibits a high PCE of 12.36% with a V-oc of 0.93 V, J(sc) of 18.86 mA cm(-2), and fill factor (FF) of 0.71, blending with a wide-band-gap polymer donor PBDB-T. Remarkably, although ATT-4 and ATT-5 exhibit broader light absorption, the devices obtained higher V-oc than that of ATT-1 mainly due to the reduced nonradiative recombination in the blend films. These results implied that side-chain engineering is an efficient approach to regulate the electronic structure and molecular packing of NFAs, which can well match with polymer donor, and obtain high PCEs of the OSCs with improved V-oc, J(sc), and FF, simultaneously.
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| 10. |
- Liu, Yu, et al.
(författare)
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Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus
- 2023
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Ingår i: Journal of Inflammation Research. - : Dove Medical Press. - 1178-7031. ; 16, s. 5367-5383
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.
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