| 1. |
- Liu, Jiale, et al.
(författare)
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STING inhibitors sensitize platinum chemotherapy in ovarian cancer by inhibiting the CGAS-STING pathway in cancer-associated fibroblasts (CAFs)
- 2024
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Ingår i: Cancer Letters. - : Elsevier. - 0304-3835 .- 1872-7980. ; 588
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy resistance in ovarian cancer hampers cure rates, with cancer-associated fibroblasts (CAFs) playing a pivotal role. Despite their known impact on cancer progression and chemotherapy resistance, the specific mechanism by which CAFs regulate the tumor inflammatory environment remains unclear. This study reveals that cisplatin facilitates DNA transfer from ovarian cancer cells to CAFs, activating the CGAS-STING-IFNB1 pathway in CAFs and promoting IFNB1 release. Consequently, this reinforces cancer cell resistance to platinum drugs. High STING expression in the tumor stroma was associated with a poor prognosis, while inhibiting STING expression enhanced ovarian cancer sensitivity. Understanding the relevance of the CGAS-STING pathway in CAFs for platinum resistance suggests targeting STING as a promising combination therapy for ovarian cancer, providing potential avenues for improved treatment outcomes.
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| 2. |
- Marcotte, Harold, et al.
(författare)
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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages
- 2024
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 121:3
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previ- ously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot suffi- ciently boost the mucosal secretory IgA response in uninfected individuals, particu- larly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgAl antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibod- ies, dimeric and secretory IgAl antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgAl form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secre- tory IgA delivered by nasal administration may potentially be exploited for the treatment Iand prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.
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| 3. |
- Zhou, Shengquan, et al.
(författare)
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MILD combustion of low calorific value gases
- 2024
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Ingår i: Progress in Energy and Combustion Science. - 0360-1285. ; 104
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Forskningsöversikt (refereegranskat)abstract
- The utilization of low calorific value gases (LCVG) in combustion devices presents particular challenges in terms of ignition and sustained combustion stability due to the presence of non-combustible components. Moderate or intense low-oxygen dilution (MILD) combustion has emerged as a promising technology for LCVG combustion, offering numerous advantages such as high combustion efficiency, reduced pollutant emissions, and increased fuel flexibility. However, the current body of research in this area is fragmented, making it challenging to draw meaningful comparisons between studies and hindering its practical application. This paper provides a comprehensive review of conventional and MILD combustion of LCVG. To understand the impact of composition on combustion, the fuels are classified based on their composition of hydrogen, carbon monoxide, methane, carbon dioxide, nitrogen, and water. We also delve into the chemical and physical effects of composition, including reaction kinetics and turbulence mixing, and provide an overview of the burners and methods used in establishing MILD combustion. Furthermore, computational fluid dynamics (CFD) models and chemical kinetics in MILD combustion are also thoroughly discussed. The presence of a large amount of dilution gas in LCVG increases the self-ignition temperature and ignition delay time of the mixture, making preheating the reactants a critical consideration. In MILD combustion, it is crucial to have an inlet reactant temperature higher than the self-ignition temperature (Tin>Tsi) to mitigate the difficulties associated with ignition and unstable combustion. The heat release in MILD combustion should be moderate to ensure that the combustion temperature does not become too high. The non-combustible components of LCVG are beneficial in this regard, as they allow for a temperature increase of less than the self-ignition temperature (ΔT
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