Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain ...mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines, pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells. In this article, we review oncogene-, tumor suppressor-, and tumor microenvironment-mediated regulation of glutamine metabolism in cancer cells. We describe the mechanism of glutamine's regulation of tumor proliferation, metastasis, and global methylation. Furthermore, we highlight the therapeutic potential of glutamine metabolism and emphasize that clinical application of in vivo assessment of glutamine metabolism is critical for identifying new ways to treat patients through glutamine-based metabolic therapy.
For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before ...surgery. For patients with clinical complete response (cCR), a "Watch and Wait" (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME). We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks.
Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients ...remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.
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•Living biobank with 80 tumor organoids was derived from treatment-naive CRC patients•Tumor organoids recapitulate histological and genetic features of original tumors•Interpatient variability in the PDO response to chemoradiation treatments•PDOs can predict locally advanced rectal cancer patient responses in the clinic
Yao et al. generated a patient-derived organoid (PDO) biobank from patients with locally advanced rectal cancer (LARC) and reported that organoids had similar molecular profiles to those of the patient tumor and that PDOs can predict LARC patient chemoradiation responses, reinforcing their value as a companion diagnostic tool in LARC treatment.
The efficient capture of SO2 is of great significance in gas‐purification processes including flue‐gas desulfurization and natural‐gas purification, but the design of porous materials with high ...adsorption capacity and selectivity of SO2 remains very challenging. Herein, the selective recognition and dense packing of SO2 clusters through multiple synergistic host–guest and guest–guest interactions by controlling the pore chemistry and size in inorganic anion (SiF62−, SIFSIX) pillared metal–organic frameworks is reported. The binding sites of anions and aromatic rings in SIFSIX materials grasp every atom of SO2 firmly via Sδ+···Fδ− electrostatic interactions and Oδ−···Hδ+ dipole–dipole interactions, while the guest–guest interactions between SO2 molecules further promote gas trapping within the pore space, which is elucidated by first‐principles density functional theory calculations and powder X‐ray diffraction experiments. These interactions afford new benchmarks for the highly efficient removal of SO2 from other gases, even if at a very low SO2 concentration. Exceptionally high SO2 capacity of 11.01 mmol g−1 is achieved at atmosphere pressure by SIFSIX‐1‐Cu, and unprecedented low‐pressure SO2 capacity is obtained in SIFSIX‐2‐Cu‐i (4.16 mmol g−1 SO2 at 0.01 bar and 2.31 mmol g−1 at 0.002 bar). More importantly, record SO2/CO2 selectivity (86–89) and excellent SO2/N2 selectivity (1285–3145) are also achieved. Experimental breakthrough curves further demonstrate the excellent performance of these hybrid porous materials in removing low‐concentration SO2.
Selective recognition and dense packing of SO2 clusters through multiple synergistic host–guest and guest–guest interactions within SiF62−‐anion‐pillared hybrid porous materials sets new benchmarks for SO2 capture. The binding sites of anions and aromatic rings in SIFSIX materials grasp every atom of SO2 firmly via Sδ+···Fδ− electrostatic interactions and Oδ−···Hδ+ dipole–dipole interactions.
Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual ...use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high-carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.
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•Comprehensive isotope tracer studies reveal TCA substrate usage for 11 major organs•These data also reveal interconversion rates between circulating nutrients•Circulatory fluxes are similar across high-carbohydrate and ketogenic diet•Futile cycling helps render internal metabolic activity robust to food choice
By infusing 15 different 13C-isotope tracers, Hui et al. quantify metabolic fluxes in mice on either high-carbohydrate or ketogenic diet. Results include interconversion fluxes between circulating metabolites and their contributions to the TCA cycle in 11 major organs. Rapid interconversion among circulating carbon carriers renders internal metabolic activity robust to diet.
Electric‐field‐controlled tunneling magnetoresistance (TMR) of magnetic tunnel junctions is considered as the milestone of ultralow power spintronic devices. Here, reversible, continuous ...magnetization rotation and manipulation is reported for TMR at room temperature in CoFeB/AlOx/CoFeB/piezoelectric structure by electric fields without the assistance of a magnetic field through strain‐mediated interaction. These results provide a new way of exploring electric‐field‐controlled spintronics.
Abstract
Selective paraffin capture from olefin/paraffin mixtures could afford high-purity olefins directly, but suffers from the issues of low separation selectivity and olefin productivity. Herein, ...we report an ultramicroporous material (PCP-IPA) with parallel-aligned linearly extending isophthalic acid units along the one-dimensional channel, realizing the efficient production of ultra-high purity C
2
H
4
and C
3
H
6
(99.99%). The periodically expanded and parallel-aligned aromatic-based units served as a paraffin nano-trap to contact with the exposed hydrogen atoms of both C
2
H
6
and C
3
H
8
, as demonstrated by the simulation studies. PCP-IPA exhibits record separation selectivity of 2.48 and separation potential of 1.20 mol/L for C
3
H
8
/C
3
H
6
(50/50) mixture, meanwhile the excellent C
2
H
6
/C
2
H
4
mixture separation performance. Ultra-high purity C
3
H
6
(99.99%) and C
2
H
4
(99.99%) can be directly obtained through fixed-bed column from C
3
H
8
/C
3
H
6
and C
2
H
6
/C
2
H
4
mixtures, respectively. The record C
3
H
6
productivity is up to 15.23 L/kg from the equimolar of C
3
H
8
/C
3
H
6
, which is 3.85 times of the previous benchmark material, demonstrating its great potential for those important industrial separations.
Abstract
The separation of xylene isomers (
para
-,
meta
-,
orth
-) remains a great challenge in the petrochemical industry due to their similar molecular structure and physical properties. Porous ...materials with sensitive nanospace and selective binding sites for discriminating the subtle structural difference of isomers are urgently needed. Here, we demonstrate the adaptively molecular discrimination of xylene isomers by employing a NbOF
5
2−
-pillared metal–organic framework (NbOFFIVE-bpy-Ni, also referred to as ZU-61) with rotational anionic sites. Single crystal X-ray diffraction studies indicate that ZU-61 with guest-responsive nanospace/sites can adapt the shape of specific isomers through geometric deformation and/or the rotation of fluorine atoms in anionic sites, thereby enabling ZU-61 to effectively differentiate xylene isomers through multiple C–H···F interactions. ZU-61 exhibited both high
meta
-xylene uptake capacity (3.4 mmol g
−1
) and
meta
-xylene/
para
-xylene separation selectivity (2.9, obtained from breakthrough curves), as well as a favorable separation sequence as confirmed by breakthrough experiments:
para
-xylene elute first with high-purity (≥99.9%), then
meta
-xylene, and
orth
-xylene. Such a remarkable performance of ZU-61 can be attributed to the type anionic binding sites together with its guest-response properties.
Subpixel object detection presents a significant challenge within the domain of hyperspectral image (HSI) processing, primarily due to the inherently limited spatial resolution of imaging ...spectrometers. For subpixel object detection, the dimensional extent of the object of interest is smaller than an individual pixel, which significantly diminishes the utility of spatial information pertaining to the object. Therefore, the efficacy of detection algorithms depends heavily on the spectral data inherent in the image. The detection of subpixel objects in hyperspectral imagery primarily relies on the suppression of the background and the enhancement of the object of interest. Hence, acquiring accurate background information from HSI images is a crucial step. In this study, an adaptive background endmember extraction for hyperspectral subpixel object detection is proposed. An adaptive scale constraint is incorporated into the background spectral endmember learning process to improve the adaptability of background endmember extraction, thus further enhancing the algorithm’s generalizability and applicability in diverse analytical scenarios. Experimental results demonstrate that the adaptive endmember extraction-based subpixel object detection algorithm consistently outperforms existing state-of-the-art algorithms in terms of detection efficacy on both simulated and real-world datasets.
Dual-energy X-ray absorptiometry (DXA) machines based on bone mineral density (BMD) represent the gold standard for osteoporosis diagnosis and assessment of fracture risk, but bone strength and ...toughness are strongly correlated with bone collagen content (CC). Early detection of osteoporosis combined with BMD and CC will provide improved predictability for avoiding fracture risk. The backscattering resonance (BR) phenomenon is present in both ultrasound (US) and photoacoustic (PA) signal transmissions through bone, and the peak frequencies of BR can be changed with BM and CC. This phenomenon can be explained by the formation of standing waves within the pores. Simulations were then conducted for the same bone µCT images and the resulting resonance frequencies were found to match those predicted using the standing wave hypothesis. Experiments were performed on the same bone sample using an 808 nm wavelength laser as the PA source and 3.5 MHz ultrasonic transducer as the US source. The backscattering resonance effect was observed in the transmitted waves. These results verify our hypothesis that the backscattering resonance phenomenon is present in both US and PA signal transmissions and can be explained using the standing waves model, which will provide a suitable method for the early detection of osteoporosis.
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