Although soluble bio-accelerators have proven effective in mitigating Cr(VI) inhibition within denitrification system, issues persist in immobilizing bio-accelerators and making them slow-release for sustained regulation. In this study, a novel strategy was proposed to fabricate immobilized bio-accelerators with controlled structure, sustained release property by 3D printing technology. Notably, the sustained release of bio-accelerators from 3D-printed bio-accelerators (3DP-B) lasted for at least 144 h. Compared to control group, 3DP-B with basic components (3DP-BB) shortened the recovery time by 1.4 folds, and the COD and NO₃^--N removal efficiency was 36.5 % and 38.0 % higher than that of natural recovery. Correspondingly, the activity of key enzymes (nitrate reductase, nitrite reductase, nitric oxide reductase, and nitrous oxide reductase), electron transfer system activity and extracellular polymer substances of denitrification biofilm maintained at relatively high levels. Furthermore, introducing 60 mg·L^-1 anthraquinone-2,6-disulfonate (AQDS) into the ink showed noticeable superiority on the bio-inhibition release over 1000 mg·L^-1 AQDS. The released AQDS facilitated the electron transport capacity by 1.25 times compared with control group. The groundbreaking findings of this study could advance the development of 3D printing technology and utilization of bio-accelerators in the field of wastewater treatment.

2024-10-01·HemaSphere

Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53‐deficient myeloma cells

Article

作者: Bellanger, Céline ; Parker, Andrew ; Maïga, Sophie ; Moreau‐Aubry, Agnès ; Derrien, Jennifer ; Devilder, Marie‐Claire ; Gomez‐Bougie, Patricia ; Touzeau, Cyrille ; Chiron, David ; Thirouard, Laura ; Pellat‐Deceunynck, Catherine ; Bouard, Louise ; Asnagli, Hélène ; Beer, Philip ; Moreau, Philippe ; Dousset, Christelle ; Durand, Romane ; Descamps, Géraldine

AbstractIn multiple myeloma, as in B‐cell malignancies, mono‐ and especially bi‐allelic TP53 gene inactivation is a high‐risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53‐deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (CTPS1), which encodes a CTP synthesis rate‐limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high MKI67 expression) or a low p53 score (synonymous with TP53 deletion and/or mutation). This overexpression of CTPS1 was associated with reduced survival in two cohorts. Using scRNA‐seq analysis in 24 patient samples, we further demonstrate that myeloma cells in the S or G2/M phase display high CTPS1 expression. Pharmacological inhibition of CTPS1 by STP‐B induced cell cycle arrest in early S phase in isogenic NCI‐H929 or XG7 TP53+/+, TP53−/−, and TP53R175H/R175H cells and in a TP53−/R123STOP patient sample. The functional annotation of transcriptional changes in 10 STP‐B‐treated myeloma cell lines revealed a decrease in protein translation and confirmed the blockade of cells into the S phase. The pharmacological inhibition of ATR, which governs the intrinsic S/G2 checkpoint, in STP‐B‐induced S‐phase arrested cells synergistically induced cell death in TP53+/+, TP53−/−, and TP53R175H/R175H isogenic cell lines (Bliss score >15). This combination induced replicative stress and caspase‐mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53−/− NCI‐H929 xenografted NOD‐scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53‐deficient patients.

2024-09-03·Cerebral Cortex

A layered microcircuit model of somatosensory cortex with three interneuron types and cell-type-specific short-term plasticity

Article

作者: Duarte, Renato ; van Albada, Sacha J ; Qi, Guanxiao ; Feldmeyer, Dirk ; Jiang, Han-Jia

AbstractThree major types of GABAergic interneurons, parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV, SOM, VIP) cells, play critical but distinct roles in the cortical microcircuitry. Their specific electrophysiology and connectivity shape their inhibitory functions. To study the network dynamics and signal processing specific to these cell types in the cerebral cortex, we developed a multi-layer model incorporating biologically realistic interneuron parameters from rodent somatosensory cortex. The model is fitted to in vivo data on cell-type-specific population firing rates. With a protocol of cell-type-specific stimulation, network responses when activating different neuron types are examined. The model reproduces the experimentally observed inhibitory effects of PV and SOM cells and disinhibitory effect of VIP cells on excitatory cells. We further create a version of the model incorporating cell-type-specific short-term synaptic plasticity (STP). While the ongoing activity with and without STP is similar, STP modulates the responses of Exc, SOM, and VIP cells to cell-type-specific stimulation, presumably by changing the dominant inhibitory pathways. With slight adjustments, the model also reproduces sensory responses of specific interneuron types recorded in vivo. Our model provides predictions on network dynamics involving cell-type-specific short-term plasticity and can serve to explore the computational roles of inhibitory interneurons in sensory functions.

100 项与 STP-B 相关的药物交易

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