Doxycycline (DOX) represents a second-generation tetracycline antibiotic that persists as a challenging-to-degrade contaminant in environmental compartments. Despite its ubiquity, scant literature ...exists on bacteria proficient in DOX degradation. This study marked a substantial advancement in this field by isolating Chryseobacterium sp. WX1 from an activated sludge enrichment culture, showcasing its unprecedented ability to completely degrade 50 mg/L of DOX within 44 h. Throughout the degradation process, seven biotransformation products were identified, revealing a complex pathway that began with the hydroxylation of DOX, followed by a series of transformations. Employing an integrated multi-omics approach alongside in vitro heterologous expression assays, our study distinctly identified the tetX gene as a critical facilitator of DOX hydroxylation. Proteomic analyses further pinpointed the enzymes postulated to mediate the downstream modifications of DOX hydroxylation derivatives. The elucidated degradation pathway encompassed several key biological processes, such as the microbial transmembrane transport of DOX and its intermediates, the orchestration of enzyme synthesis for transformation, energy metabolism, and other gene-regulated biological directives. This study provides the first insight into the adaptive biotransformation strategies of Chryseobacterium under DOX-induced stress, highlighting the potential applications of this strain to augment DOX removal in wastewater treatment systems containing high concentrations of DOX.
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•A potent DOX-degrading bacterium Chryseobacterium sp. WX1 was isolated.•Transformation products lose antibacterial efficacy against Gram-positive bacteria.•Multi-omic was applied to profile the mechanism of DOX biodegradation.•The hydroxylation of DOX was driven by the tetX gene.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thallium (Tl) is widely used in various industries, which increases the risk of leakage into the environment. Since Tl is highly toxic, it can do a great harm to human health and ecosystem. In order ...to explore the response of freshwater sediment microorganisms to sudden Tl spill, metagenomic technique was used to elucidate the changes of microbial community composition and functional genes in river sediments. Tl pollution could have profound impacts on microbial community composition and function. Proteobacteria remained the dominance in contaminated szediments, indicating that it had a strong resistance to Tl contamination, and Cyanobacteria also showed a certain resistance. Tl pollution also had a certain screening effect on resistance genes and affected the abundance of resistance genes. Metal resistance genes (MRGs) and antibiotic resistance genes (ARGs) were enriched at the site near the spill site, where Tl concentration was relatively low among polluted sites. When Tl concentration was higher, the screening effect was not obvious and the resistance genes even became lower. Moreover, there was a significant correlation between MRGs and ARGs. In addition, co-occurrence network analysis showed that Sphingopyxis had the most links with resistance genes, indicating that it was the biggest potential host of resistance genes. This study provided new insight towards the shifts in the composition and function of microbial communities after sudden serious Tl contamination.
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•Thallium spill altered microbial composition and function in sediments.•Proteobacteria dominated the microbial community and Cyanobacteria had a strong metal resistance.•Thallium pollution played a role in screening resistance genes in the environment.•Sphingopyxis was the largest potential host of resistance genes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mangrove wetlands, as one of the natural ecosystems with the most ecological services, have garnered widespread attention about their microbial driven biogeochemical cycling. Urbanization have led to ...different spatial patterns of environmental conditions and microbial communities in mangroves. However, viruses, as the pivotal drivers of biogeochemical cycling in mangroves, remain inadequately explored in terms of how their ecological potential and complex interactions with host respond to functional zonings. To address this knowledge gap, we conducted a comprehensive investigation on the structural and functional properties of temperate and lytic viruses in mangrove wetlands from different functional zonings by jointly using high-throughput sequencing, prokaryotic and viral metagenomics. Multiple environmental factors were found to significantly influence the taxonomic and functional composition, as well as lysogen-lysis decision-making of mangrove viruses. Furthermore, enriched auxiliary metabolic genes (AMGs) involved in methane, nitrogen and sulfur metabolism, and heavy metal resistance were unveiled in mangrove viruses, whose community composition was closely related to lifestyle and host. The virus-host pairs with different lifestyles were also discovered to react to environmental changes in different ways, which provided an empirical evidence for how virus and bacteria dynamics were specific to viral lifestyles in nature. This study expands our comprehension of the intricate interactions among virus, prokaryotic host and the environment in mangrove wetlands from multiple perspectives, including viral lifestyles, virus-host interactions, and habitat dependence. Importantly, it provides a new ecological perspective on how mangrove viruses are adapted to the stress posed by urbanization.
•Mangrove viruses were explored by integration of prokaryotic and viral metagenomics.•Lifestyle, host and habitat shaped the viral taxonomic and functional composition.•Abundant AMGs revealed the importance of viruses in mangrove biogeochemical cycling.•The interaction mechanism of virus-host-environment systems varied with lifestyle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The magnesium oxide modified TiO2 nanotube arrays (TiO2 NTs) was prepared to investigate the photoelectrochemical (PEC) cathodic protection performance to 304 stainless steel (SS 304). With the ...annealing treatment at different temperature, the surface of the modified materials changed remarkably. The film-like Mg(OH)2 obtained at 400°C transformed to MgO particles after treatment at 500°C and 600°C. Further thermal processing at 700°C enables MgTixOy@TiO2 shell-core structure. Using photoelectrochemical approaches to study the series samples, the cathodic protection performance of the modified TiO2 NTs has significantly improved. The magnesium oxides modified TiO2 NTs treated at 600°C (Ti-Mg-O 600) shows the best PEC cathodic protection to the underneath steel. Further investigation shows that the highly enhanced PEC cathodic protection performance of Ti-Mg-O 600 was attributed to the effective separation of photogenerated carriers, the increase of carrier concentration and the negative shift of the conduction band potential.
•The magnesium oxides modified TiO2 NTs were prepared to investigate the PEC cathodic protection performance of 304 ss.•The surfaces of the modified TiO2 NTs changed obviously with the annealing treatment at different temperatures.•The PEC cathodic protection performance of the modified TiO2 NTs was significantly improved.•The enhanced PEC cathodic protection performance of modified TiO2 NTs was analyzed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The synergistic mechanism of hydrogen treatment technology and heterogeneous structure was firstly reported to enhance the photoelectrochemical properties of SrTiO3/TiO2 composite. The SrTiO3 ...nanoparticles were successfully synthesized on the surface of TiO2 nanotube arrays to form SrTiO3/TiO2 heterostructure by a hydrothermal method. The heterogeneous structure was further optimized by hydrogen treatment under calcinations to prepare the hydrogen-treated SrTiO3/TiO2 nanotube arrays heterojunction composite (H-SrTiO3/TiO2). The photoelectrochemical performance of H-SrTiO3/TiO2 was significantly enhanced, whose photocurrent density was 3 times of that of hydrogen treated TiO2 (H-TiO2) and 1.5 times of that of SrTiO3/TiO2 heterostructures. The improved photoelectrochemical performance of H-SrTiO3/TiO2 can be attributed to the synergistic effect of hydrogen treatment and heterojunction, which results in the enhancement of light absorption and the increase of photogenerated carrier concentration.
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•H-SrTiO3/TiO2 was successfully prepared to investigate its photoelectrochemical performance.•The photoelectrochemical performance of H-SrTiO3/TiO2 was significantly enhanced.•Hydrogen treatment and heterojunction synergistic effect can improve photoelectrochemical performance of H-SrTiO3/TiO2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Multiple myeloma (MM) is a heterogenous plasma cell malignancy. About 30-40% of newly diagnosed and 20-60% of relapsed/refractory MM patients carry 1q21 amplification worldwide, a ...high-risk indicator for poor prognosis in RRMM. Different BCL-2 family anti-death proteins play important roles in MM survival and drug resistance. High expression of BCL-2 due to t (11;14) renders cell vulnerability to BCL-2 antagonist, however, patients carrying other genetic abnormality including 1q21 amplification have limited response to the newly emerged treatment choice. With MCL-1 upregulation accompanied with 1q21 amplification, we tested whether BCL-2 antagonist combined with IMiDs (immunomodulatory imide drugs), improves cell killing in high-risk MM patient models, including those resistant to bortezomib and lenalidomide. For that aim, we studied APG-2575, a novel and potent BCL-2 inhibitor developed by Ascentage Pharma Group and it is currently in clinical trials for hematologic malignances, including MM.
Methods
1. Cells were treated with APG-2575 single agent or in combination with lenalidomide;
2. Cell line viability was assessed by CellTiter-Glo (CTG) assay;
3. Flow cytometry analysis was used to detect CD138+ cell surface marker in primary cells derived from MM patients;
4. Western blot analysis for BCL-2 family and IMiD signaling proteins.
Results
We first determined the cell sensitivity of APG-2575 as a single agent in a panel of MM cell lines, and as expected, those carrying t (11;14) were very sensitive to APG-2575, with low IC50 values ranging 7-23 nM. The IC50 values for cells carrying other genetic markers were greater than 5-10 μM.
We then evaluated cell-death inducing activity of APG-2575 in MM patient-derived primary cells ex vivo, which were freshly prepared from patients’ bone marrow aspirates. Primary cells were treated with APG-2575 or ABT-199 (venetoclax) for 18-24 hours, and the loss of CD138 surface marker was used to quantify cell death. As shown in Figure 1a, APG-2575 induced cell death (CD138+ loss) in a dose-dependent manner, and significant cell death was observed at 0.37-3.3 μM of APG-2575, indicating primary cells more sensitive than MM cell lines. Interestingly, the sensitivity to APG-2575 is similar in primary MM cells with or without 1q21 amplification.
Since moderate cell death inducing activity was observed in MM cells when APG-2575 used as a single agent, we combined APG-2575 with lenalidomide. Cell death was increased in the combination groups compared with single agent, and it was dose-dependent (Figure 1b).Similar enhanced antiproliferative activity was confirmed in RPMI 8226 cell line, which carries 1q21 amplification (Figure 1c).
We furthered to understand the mechanism of action (MoA) of this combination. In Figure 1d, Western blot analysis of RPMI 8226 cell line revealed that IKZF1 and IKZF3 proteins from the NF-KB pathway were downregulated by lenalidomide. And the decrease of MCL-1 protein and the strong induction of pro-death protein BAK were evident in the combination group of APG-2575 and lenalidomide, which helps to illustrate MoA underlying the synergistic effect of APG-2575 and lenalidomide in MM models.
Conclusions
In both cell lines and primary samples derived from MM patients, APG-2575 demonstrates cell death inducing activity as a single agent, and enhanced/synergistic effects when it combines with lenalidomide in RRMM resistant to lenalidomide and bortezomib. The combination decreases IKZF1, IKZF3 and MCL-1 proteins, and upregulates pro-death protein BAK, thus providing a strong rationale to combine BCL-2 inhibitor and lenalidomide to treat high-risk patient populations carrying 1q21 amplification.
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FU:Ascentage Pharma (SuZhou) Co., Ltd: Other: research agreement contract . Yin:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Mao:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Deng:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Fang:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Yang:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests. Zhai:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Promotion of ICD via Nanotechnology Qin, Yang; Zhang, Haitao; Li, Yunxian ...
Macromolecular bioscience,
September 2023, Volume:
23, Issue:
9
Journal Article
Peer reviewed
Immunotherapy represents the most promising treatment strategy for cancer, but suffers from compromised therapeutic efficiency due to low immune activity of tumor cells and an immunosuppressive ...microenvironment, which significantly hampers the clinical translations of this treatment strategy. To promote immunotherapy with desired therapeutic efficiency, immunogenic cell death (ICD), a particular type of death capable of reshaping body's antitumor immune activity, has drawn considerable attention due to the potential to stimulate a potent immune response. Still, the potential of ICD effect remains unsatisfactory because of the intricate tumor microenvironment and multiple drawbacks of the used inducing agents. ICD has been thoroughly reviewed so far with a general classification of ICD as a kind of immunotherapy strategy and repeated discussion of the related mechanism. However, there are no published reviews, to the authors’ knowledge, providing a systematic summarization on the enhancement of ICD via nanotechnology. For this purpose, this review first discusses the four stages of ICD according to the development mechanisms, followed by a comprehensive description on the use of nanotechnology to enhance ICD in the corresponding four stages. The challenges of ICD inducers and possible solutions are finally summarized for future ICD‐based enhanced immunotherapy.
This review summarizes four leading strategies used to promote the therapeutic effects of immunogenic cell death (ICD) via nanotechnology, including increasing the localized concentration of an ICD inducer in tumor, inducing various intracellular reactions, catalyzing the activity of antigen‐presenting cells, and protecting the function of cytotoxic T cells, together with an overview of the state‐of‐the‐art clinical applications of ICD via nanotechnology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The synergistic mechanism of hydrogen treatment technology and heterogeneous structure was firstly reported to enhance the photoelectrochemical properties of SrTiO3/TiO2 composite. The SrTiO3 ...nanoparticles were successfully synthesized on the surface of TiO2 nanotube arrays to form SrTiO3/TiO2 heterostructure by a hydrothermal method. The heterogeneous structure was further optimized by hydrogen treatment under calcinations to prepare the hydrogen-treated SrTiO3/TiO2 nanotube arrays heterojunction composite (H-SrTiO3/TiO2). The photoelectrochemical performance of H-SrTiO3/TiO2 was significantly enhanced, whose photocurrent density was 3 times of that of hydrogen treated TiO2 (H-TiO2) and 1.5 times of that of SrTiO3/TiO2 heterostructures. The improved photoelectrochemical performance of H-SrTiO3/TiO2 can be attributed to the synergistic effect of hydrogen treatment and heterojunction, which results in the enhancement of light absorption and the increase of photogenerated carrier concentration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Heterojunction connecting by interface chemical bonds is a promising method as it can provide more efficient route for photogenerated charge separation. In this work, the oxygen vacancies are ...introduced into the surface of SrTiO3 by a one‐step hydrogenation method. SrTiO3 with oxygen vacancy (STO) is compounded with Cd0.5Zn0.5S (CZS) by hydrothermal method, resulting in the successful formation of a good heterojunction structure. By comparing with the pristine SrTiO3/CZS composites, it is found that the oxygen vacancies play an important role in the formation of excellent heterojunctions, in addition to the traditional reports as charge traps and adsorption sites or the ability to cause band changes. X‐ray photoelectron spectroscopy (XPS) and high‐resolution transmission electron microscope results disclose that S2− enters the oxygen vacancy on the (110) plane of STO and interacts with the adjacent Ti in the van der Waals force to form the Ti‐O‐S group, which results in the formation of excellent heterojunctions and makes the CZS nanoparticles growth evenly on the STO nanoplates. Furthermore, the formation of excellent heterojunction and the introduction of interfaced oxygen vacancy significantly improve the separation efficiency of photogenerated charge carriers, which dramatically increases the photoelectrochemical performance.
Heterojunction connecting by interface chemical bonds is a promising method as it can provide more efficient route for photogenerated charge separation. In this work, oxygen vacancy forming on the surface of SrTiO3 is employed to fabricate heterojunction with ZnCdS, which provides an excellent interface for photogenerated charge transfer and separation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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