Slow TCA flux and ATP production in primary solid tumours but not metastases.

Tissues derive ATP from two pathways-glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electron transport chain. Most energy in mammals is produced via TCA metabolism1. In tumours, however, the absolute rates of these pathways remain unclear. Here we optimize tracer infusion approaches to measure the rates of glycolysis and the TCA cycle in healthy mouse tissues, Kras-mutant solid tumours, metastases and leukaemia. Then, given the rates of these two pathways, we calculate total ATP synthesis rates. We find that TCA cycle flux is suppressed in all five primary solid tumour models examined and is increased in lung metastases of breast cancer relative to primary orthotopic tumours. As expected, glycolysis flux is increased in tumours compared with healthy tissues (the Warburg effect2,3), but this increase is insufficient to compensate for low TCA flux in terms of ATP production. Thus, instead of being hypermetabolic, as commonly assumed, solid tumours generally produce ATP at a slower than normal rate. In mouse pancreatic cancer, this is accommodated by the downregulation of protein synthesis, one of this tissue's major energy costs. We propose that, as solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.

Mitochondrial ATP generation is more proteome efficient than glycolysis.

Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. We accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

Spatially resolved isotope tracing reveals tissue metabolic activity.

Isotope tracing has helped to determine the metabolic activities of organs. Methods to probe metabolic heterogeneity within organs are less developed. We couple stable-isotope-labeled nutrient infusion to matrix-assisted laser desorption ionization imaging mass spectrometry (iso-imaging) to quantitate metabolic activity in mammalian tissues in a spatially resolved manner. In the kidney, we visualize gluconeogenic flux and glycolytic flux in the cortex and medulla, respectively. Tricarboxylic acid cycle substrate usage differs across kidney regions; glutamine and citrate are used preferentially in the cortex and fatty acids are used in the medulla. In the brain, we observe spatial gradations in carbon inputs to the tricarboxylic acid cycle and glutamate under a ketogenic diet. In a carbohydrate-rich diet, glucose predominates throughout but in a ketogenic diet, 3-hydroxybutyrate contributes most strongly in the hippocampus and least in the midbrain. Brain nitrogen sources also vary spatially; branched-chain amino acids contribute most in the midbrain, whereas ammonia contributes in the thalamus. Thus, iso-imaging can reveal the spatial organization of metabolic activity.

Sulfonate Functional Ultramicroporous Materials with Suitable Pore Size and Layer-Stacked Structure for C4 Olefins Purification.

Selective recognition of 1,3-butadiene from complex olefin isomers is vital for 1,3-butadiene purification, but the lack of porous materials with suitable pore structures results in poor selectivity and low capacity in C4 olefin separation. Herein, two sulfonate-functionalized organic frameworks, ZU-601 and ZU-602, are designed and show impressive separation performance toward C4 olefins. Benefiting from the suitable aperture size caused by the flexibility of coordinated organic ligand, ZU-601, ZU-602 that are pillared with different sulfonate anions could discriminate C4 olefin isomers with high uptake ratio: 1,3-butadiene/1-butene (207), 1,3-butadiene/trans-2-butene (10.1). Meanwhile, their layer-stacked structure enables the utilization of both intra- and interlayer space, enhancing the accommodation of guest molecules. ZU-601 exhibits record high 1,3-butadiene adsorption capacity of 2.90 mmol g-1 (0.5 bar, 298 K) among the reported flexible porous materials with high 1,3-butadiene/1-butene selectivity. The breakthrough experiments confirm their superior separation ability even for all five C4 olefin isomers, and the molecular-level structural change is well elucidated via powder, crystal analysis, and simulation studies. The work provides ideas toward advanced materials design with simultaneous high separation capacity and high separation selectivity for challenging separations.

Ultra-small, low-cost, and simple-to-control PSP projector based on SLCD technology.

Demand for ultra-small, inexpensive, and high-accurate 3D shape measurement devices is growing rapidly, especially in the industrial and consumer electronics sectors. Phase shifting profilometry (PSP) is a powerful candidate due to its advantages of high accuracy, great resolution, and insensitivity to ambient light. As a key component in PSP, the projector used to generate the phase-shifting sinusoidal fringes must be ultra-small (several millimeters), low-cost, and simple to control. However, existing projection methods make it difficult to meet these requirements simultaneously. In this paper, we present a modern technique that can be used to fabricate the desired projector. A specifically designed device based on segmented liquid crystal display (SLCD) technology is used to display the projected patterns, and a cylindrical lens is used as the projection lens. The SLCD device can display four sets of specific filled binary patterns, each yielding a sinusoidal fringe, and all four sinusoidal fringes satisfy the four-step phase shift relation. 3D shape measurement experiments verify the performance of the projector. Considering that the size of SLCD devices can be reduced to a few millimeters, the proposed technique can be easily used to manufacture ultra-small, low-cost, and simple-to-control PSP projectors.

One-Step Butadiene Purification in a Sulfonate-Functionalized Metal-Organic Framework through Synergistic Separation Mechanism.

Porous materials that could recognize specific molecules from complex mixtures are of great potential in improving the current energy-intensive multistep separation processes. However, due to the highly similar structures and properties of the mixtures, the design of desired porous materials remains challenging. Herein, a sulfonate-functionalized metal-organic framework ZU-609 with suitable pore size and pore chemistry is designed for 1,3-butadiene (C4H6) purification from complex C4 mixtures. The sulfonate anions decorated in the channel achieve selective recognition of C4H6 from other C4 olefins with subtle polarity differences through C-H⋅⋅⋅O-S interactions, affording recorded C4H6/trans-2-C4H8 selectivity (4.4). Meanwhile, the shrunken mouth of the channel with a suitable pore size (4.6 Å) exhibits exclusion effect to the larger molecules cis-2-C4H8, iso-C4H8, n-C4H10 and iso-C4H10. Benefiting from the moderate C4 olefins binding affinity exhibited by sulfonate anions, the adsorbed C4H6 could be easily regenerated near ambient conditions. Polymer-grade 1,3-butadiene (99.5 %) is firstly obtained from 7-component C4 mixtures via one adsorption-desorption cycle. The work demonstrates the great potential of synergistic recognition of size-sieving and thermodynamically equilibrium in dealing with complex mixtures.

Activation of the integrated stress response rewires cardiac metabolism in Barth syndrome.

Barth Syndrome (BTHS) is an inherited cardiomyopathy caused by defects in the mitochondrial transacylase TAFAZZIN (Taz), required for the synthesis of the phospholipid cardiolipin. BTHS is characterized by heart failure, increased propensity for arrhythmias and a blunted inotropic reserve. Defects in Ca2+-induced Krebs cycle activation contribute to these functional defects, but despite oxidation of pyridine nucleotides, no oxidative stress developed in the heart. Here, we investigated how retrograde signaling pathways orchestrate metabolic rewiring to compensate for mitochondrial defects. In mice with an inducible knockdown (KD) of TAFAZZIN, and in induced pluripotent stem cell-derived cardiac myocytes, mitochondrial uptake and oxidation of fatty acids was strongly decreased, while glucose uptake was increased. Unbiased transcriptomic analyses revealed that the activation of the eIF2α/ATF4 axis of the integrated stress response upregulates one-carbon metabolism, which diverts glycolytic intermediates towards the biosynthesis of serine and fuels the biosynthesis of glutathione. In addition, strong upregulation of the glutamate/cystine antiporter xCT increases cardiac cystine import required for glutathione synthesis. Increased glutamate uptake facilitates anaplerotic replenishment of the Krebs cycle, sustaining energy production and antioxidative pathways. These data indicate that ATF4-driven rewiring of metabolism compensates for defects in mitochondrial uptake of fatty acids to sustain energy production and antioxidation.

DegU-mediated suppression of carbohydrate uptake in Listeria monocytogenes increases adaptation to oxidative stress.

The foodborne bacterial pathogen Listeria monocytogenes exhibits remarkable survival capabilities under challenging conditions, severely threatening food safety and human health. The orphan regulator DegU is a pleiotropic regulator required for bacterial environmental adaptation. However, the specific mechanism of how DegU participates in oxidative stress tolerance remains unknown in L. monocytogenes. In this study, we demonstrate that DegU suppresses carbohydrate uptake under stress conditions by altering global transcriptional profiles, particularly by modulating the transcription of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS)-related genes, such as ptsH, ptsI, and hprK. Specifically, in the absence of degU, the transcripts of ptsI are significantly upregulated and those of hprK are significantly downregulated in response to copper ion-induced stress. Overexpression of ptsI significantly increases bacterial growth in vitro, while overexpression of hprK leads to a decrease in growth. We further demonstrate that DegU directly senses oxidative stress, downregulates ptsI transcription, and upregulates hprK transcription. Additionally, through an electrophoretic mobility shift assay, we demonstrate that DegU directly regulates the transcription of ptsI and hprK by binding to specific regions within their respective promoter sequences. Notably, the putative pivotal DegU binding sequence for ptsI is located from 38 to 68 base pairs upstream of the ptsH transcription start site (TSS), whereas for hprK, it is mapped from 36 to 124 base pairs upstream of the hprK TSS. In summary, we elucidate that DegU plays a significant role in suppressing carbohydrate uptake in response to oxidative stress through the direct regulation of ptsI and hprK.ImportanceUnderstanding the adaptive mechanisms employed by Listeria monocytogenes in harsh environments is of great significance. This study focuses on investigating the role of DegU in response to oxidative stress by examining global transcriptional profiles. The results highlight the noteworthy involvement of DegU in this stress response. Specifically, DegU acts as a direct sensor of oxidative stress, leading to the modulation of gene transcription. It downregulates ptsI transcription while it upregulates hprK transcription through direct binding to their promoters. Consequently, these regulatory actions impede bacterial growth, providing a defense mechanism against stress-induced damage. These findings gained from this study may have broader implications, serving as a reference for studying adaptive mechanisms in other pathogenic bacteria and aiding in the development of targeted strategies to control L. monocytogenes and ensure food safety.

Deep learning-based multiomics integration model for predicting axillary lymph node metastasis in breast cancer.

Aim: To develop a deep learning-based multiomics integration model. Materials & methods: Five types of omics data (mRNA, DNA methylation, miRNA, copy number variation and protein expression) were used to build a deep learning-based multiomics integration model via a deep neural network, incorporating an attention mechanism that adaptively considers the weights of multiomics features. Results: Compared with other methods, the deep learning-based multiomics integration model achieved remarkable results, with an area under the curve of 0.89 (95% CI: 0.863-0.910). Conclusion: The deep learning-based multiomics integration model achieved promising results and is an effective method for predicting axillary lymph node metastasis in breast cancer.

Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.

The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP activated protein kinase (AMPK), which in turn directly suppresses sterol regulatory element-binding protein 1 (SREBP1)-directed transcription of its direct targets including the BCAT2 branched-chain amino acid transaminase 2) gene. BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to α-ketoglutarate (α-KG) thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with this intractable disease.

A Robust Metal-Organic Framework with Scalable Synthesis and Optimal Adsorption and Desorption for Energy-Efficient Ethylene Purification.

Adsorptive separation is an energy-efficient alternative, but its advancement has been hindered by the challenge of industrially potential adsorbents development. Herein, a novel ultra-microporous metal-organic framework ZU-901 is designed that satisfies the basic criteria raised by ethylene/ethane (C2 H4 /C2 H6 ) pressure swing adsorption (PSA). ZU-901 exhibits an "S" shaped C2 H4 curve with high sorbent selection parameter (65) and could be mildly regenerated. Through green aqueous-phase synthesis, ZU-901 is easily scalable with 99 % yield, and it is stable in water, acid, basic solutions and cycling breakthrough experiments. Polymer-grade C2 H4 (99.51 %) could be obtained via a simulating two-bed PSA process, and the corresponding energy consumption is only 1/10 of that of simulating cryogenic distillation. Our work has demonstrated the great potential of pore engineering in designing porous materials with desired adsorption and desorption behavior to implement an efficient PSA process.

Modulating Chemical Environments of Metal-Organic Framework-Supported Molybdenum(VI) Catalysts for Insights into the Structure-Activity Relationship in Cyclohexene Epoxidation.

Solid supports are crucial in heterogeneous catalysis due to their profound effects on catalytic activity and selectivity. However, elucidating the specific effects arising from such supports remains challenging. We selected a series of metal-organic frameworks (MOFs) with 8-connected Zr6 nodes as supports to deposit molybdenum(VI) onto to study the effects of pore environment and topology on the resulting Mo-supported catalysts. As characterized by X-ray absorption spectroscopy (XAS) and single-crystal X-ray diffraction (SCXRD), we modulated the chemical environments of the deposited Mo species. For Mo-NU-1000, the Mo species monodentately bound to the Zr6 nodes were anchored in the microporous c-pore, but for Mo-NU-1008 they were bound in the mesopore of Mo-NU-1008. Both monodentate and bidentate modes were found in the mesopore of Mo-NU-1200. Cyclohexene epoxidation with H2O2 was probed to evaluate the support effect on catalytic activity and to unveil the resulting structure-activity relationships. SCXRD and XAS studies demonstrated the atomically precise structural differences of the Mo binding motifs over the course of cyclohexene epoxidation. No apparent structural change was observed for Mo-NU-1000, whereas the monodentate mode of Mo species in Mo-NU-1008 and the monodentate and bidentate Mo species in Mo-NU-1200 evolved to a new bidentate mode bound between two adjacent oxygen atoms from the Zr6 node. This work demonstrates the great advantage of using MOF supports for constructing heterogeneous catalysts with modulated chemical environments of an active species and elucidating structure-activity relationships in the resulting reactions.

Kinetic-Sieving of Carbon Dioxide from Acetylene through a Novel Sulfonic Ultramicroporous Material.

The engineering and tailoring of porous materials to realize the precise discrimination of CO2 and C2 H2 , with almost identical kinetic diameters, is a challenging task. We herein report the first example of the kinetic-sieving of relatively larger molecule of C2 H2 from CO2 by a novel sulfonic anion-pillared hybrid ultramicroporous materials of ZU-610a. Specifically, ZU-610 constructed from copper(II), isonicotinic acid and 1,2-ethanedisulfonic acid is synthesized and shows the preferential affinity for C2 H2 over CO2 . After the post-synthetic heat treatment of ZU-610, ZU-610a with a contracted aperture is obtained. Interestingly, the C2 H2 -selctive ZU-610 was reversed to the CO2 -selective ZU-610a. High purity C2 H2 (>99.5 %) could be directly obtained from the dynamic breakthrough experiments on an equimolar C2 H2 /CO2 mixture at 298 K. This study provides guidance for the design of adsorbents aimed at separation systems with similar kinetic diameter.

Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: A prospective cohort study.

BACKGROUND: 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). METHODS AND FINDINGS: 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. Ranging from complete tumor regression (pathological tumor regression grade 0; pTRG0) to poor regression (pTRG3), the ctDNA clearance rate during nCRT showed a significant decreasing trend (95.7%, 77.8%, 71.1%, and 66.7% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.008), while the detection rate of acquired mutations in ctDNA showed an increasing trend (3.8%, 8.3%, 19.2%, and 23.1% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.02). Univariable logistic regression showed that ctDNA clearance was associated with a low probability of non-pCR (odds ratio = 0.11, 95% confidence interval [95% CI] = 0.01 to 0.6, P = 0.04). A risk score predictive model, which incorporated both ctDNA (i.e., features of baseline ctDNA, ctDNA clearance, and acquired mutation status) and MRI tumor regression grade (mrTRG), was developed and demonstrated improved performance in predicting pCR/non-pCR (area under the curve [AUC] = 0.886, 95% CI = 0.810 to 0.962) compared with models derived from only ctDNA (AUC = 0.818, 95% CI = 0.725 to 0.912) or only mrTRG (AUC = 0.729, 95% CI = 0.641 to 0.816). The detection of potential colorectal cancer (CRC) driver genes in ctDNA after nCRT indicated a significantly worse recurrence-free survival (RFS) (hazard ratio [HR] = 9.29, 95% CI = 3.74 to 23.10, P < 0.001). Patients with detectable driver mutations and positive high-risk feature (HR_feature) after surgery had the highest recurrence risk (HR = 90.29, 95% CI = 17.01 to 479.26, P < 0.001). Limitations include relatively small sample size, lack of independent external validation, no serial ctDNA testing after surgery, and a relatively short follow-up period. CONCLUSIONS: 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.

Energy-efficient separation alternatives: metal-organic frameworks and membranes for hydrocarbon separation.

Hydrocarbon separation is one of the most critically important and complex industrial separation processes, offering versatile bulk chemicals and vital support to the national economy. Traditional separation technologies, such as cryogenic distillation and solvent extraction, are energy-intensive and cause serious environmental stress. Moreover, the growth of industries and technologies and the greater requirements for products (e.g., purity) lead to challenges that cannot be met using traditional separation methods. Adsorptive and membrane-based separations are recognized as energy-efficient alternatives by which to revolutionize the current energy-intensive conditions and satisfy the new demands. This critical review presents the recent progress in metal-organic frameworks (MOFs) and related membranes (e.g., continuous MOF membranes and mixed-matrix membranes) for hydrocarbon separation. The contributions of the underlying separation mechanisms (e.g., enthalpy-driven thermodynamic equilibrium, molecular sieving, kinetic separation based on molecular size, and combined mechanisms) and the adopted strategies (e.g., defect and microstructure control, membrane thickness and interfacial compatibility) to the breaking of trade-off (e.g., permeability/selectivity and capacity/selectivity) and the design of novel materials and processing technologies are discussed. Moreover, this review also summarizes the potential barriers that exist from the academic to the ultimate industrial implementations and the prospects of future development.

Diagnosis of Bone Mineral Density Based on Backscattering Resonance Phenomenon Using Coregistered Functional Laser Photoacoustic and Ultrasonic Probes.

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.

Benchmark C2 H2 /CO2 Separation in an Ultra-Microporous Metal-Organic Framework via Copper(I)-Alkynyl Chemistry.

Separation of acetylene from carbon dioxide remains a daunting challenge because of their very similar molecular sizes and physical properties. We herein report the first example of using copper(I)-alkynyl chemistry within an ultra-microporous MOF (CuI @UiO-66-(COOH)2 ) to achieve ultrahigh C2 H2 /CO2 separation selectivity. The anchored CuI ions on the pore surfaces can specifically and strongly interact with C2 H2 molecule through copper(I)-alkynyl π-complexation and thus rapidly adsorb large amount of C2 H2 at low-pressure region, while effectively reduce CO2 uptake due to the small pore sizes. This material thus exhibits the record high C2 H2 /CO2 selectivity of 185 at ambient conditions, significantly higher than the previous benchmark ZJU-74a (36.5) and ATC-Cu (53.6). Theoretical calculations reveal that the unique π-complexation between CuI and C2 H2 mainly contributes to the ultra-strong C2 H2 binding affinity and record selectivity. The exceptional separation performance was evidenced by breakthrough experiments for C2 H2 /CO2 gas mixtures. This work suggests a new perspective to functionalizing MOFs with copper(I)-alkynyl chemistry for highly selective separation of C2 H2 over CO2 .

Implications of gut microbiota dysbiosis and metabolic changes in prion disease.

Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the structure of the gut microbiota and metabolic changes by 16S rRNA sequencing and LC-MS-based metabolomics respectively as multi-omic analyses. Additionally, SCFAs and common amino acids were detected by GC-MS and UPLC respectively. Enteric changes induced by prion disease affected both structure and abundances of the gut microbiota. The gut microbiota of infected mice displayed greater numbers of Proteobacteria and less Saccharibacteria at the phylum level and more Lactobacillaceae and Helicobacteraceae and less Prevotellaceae and Ruminococcaceae at the family level. A total of 145 fecal metabolites were found to be significantly different in prion infection, and most (114) of these were lipid metabolites. Using KEGG pathway enrichment analysis, we found that 3 phosphatidylcholine (PC) compounds significantly decreased and 4 hydrophobic bile acids significantly increased. Decreases of 8 types of short-chain acids (SCFAs) and increases of Cys and Tyr and decreases of His, Trp, and Arg were observed in prion infection. Correlation analysis indicated that the gut microbiota changes observed in our study may have been the shared outcome of prion disease. These findings suggest that prion disease can cause significant shifts in the gut microbiota. Certain bacterial taxa can then respond to the resulting change to the enteric environment by causing dramatic shifts in metabolite levels. Our data highlight the health impact of the gut microbiota and related metabolites in prion disease.

Rational Design of Microporous MOFs with Anionic Boron Cluster Functionality and Cooperative Dihydrogen Binding Sites for Highly Selective Capture of Acetylene.

Separation of acetylene (C2 H2 ) from carbon dioxide (CO2 ) or ethylene (C2 H4 ) is important in industry but limited by the low capacity and selectivity owing to their similar molecular sizes and physical properties. Herein, we report two novel dodecaborate-hybrid metal-organic frameworks, MB12 H12 (dpb)2 (termed as BSF-3 and BSF-3-Co for M=Cu and Co), for highly selective capture of C2 H2 . The high C2 H2 capacity and remarkable C2 H2 /CO2 selectivity resulted from the unique anionic boron cluster functionality as well as the suitable pore size with cooperative proton-hydride dihydrogen bonding sites (B-Hδ- ⋅⋅⋅Hδ+ -C≡C-Hδ+ ⋅⋅⋅Hδ- -B). This new type of C2 H2 -specific functional sites represents a fresh paradigm distinct from those in previous leading materials based on open metal sites, strong electrostatics, or hydrogen bonding.

Separation of Xe from Kr with Record Selectivity and Productivity in Anion-Pillared Ultramicroporous Materials by Inverse Size-Sieving.

The separation of xenon/krypton (Xe/Kr) mixture is of great importance to industry, but the available porous materials allow the adsorption of both, Xe and Kr only with limited selectivity. Herein we report an anion-pillared ultramicroporous material NbOFFIVE-2-Cu-i (ZU-62) with finely tuned pore aperture size and structure flexibility, which for the first time enables an inverse size-sieving effect in separation along with record Xe/Kr selectivity and ultrahigh Xe capacity. Evidenced by single-crystal X-ray diffraction, the rotation of anions and pyridine rings upon contact of larger-size Xe atoms adapts cavities to the shape/size of Xe and allows strong host-Xe interaction, while the smaller-size Kr is excluded. Breakthrough experiments confirmed that ZU-62 has a real practical potential for producing high-purity Kr and Xe from air-separation byproducts, showing record Kr productivity (206 mL g-1 ) and Xe productivity (42 mL g-1 , in desorption) as well as good recyclability.