Quality evaluation of natural monomer flavors for Chinese tobacco industry based on dual mode combined Fourier transform ion cyclotron resonance mass spectrometry and isotopic fine structures.

RATIONALE: Natural monomer flavors can modify the taste of cigarettes. However, no report was published to establish the quality control method for their chemical compositions. METHODS: In this study, licorice, a traditional natural monomer flavor used in tobacco aroma processing, was selected, and the fingerprint was developed by high-performance liquid chromatography (HPLC). Next, the chemical markers of samples from different places of origin were discovered by multivariate statistical analysis. Then, its chemical constituents were identified by combination of HPLC-Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), direct infusion FT-ICR-MS (DI-FT-ICR-MS), and the technology of isotopic fine structures (IFSs). Moreover, its characteristic constituents were quantitatively analyzed using HPLC. RESULTS: The 14 common peaks were assigned in the fingerprint, and 8 of them were considered as qualitative markers by multivariate statistical analysis. A total of 42 chemical constituents were detected using HPLC-FT-ICR-MS, and 13 of them were unambiguously identified by references. Meanwhile, the elemental compositions of other eight unknown chemical components were decisively determined using IFSs. Subsequently, the contents of five characteristic constituents in 11 batches of samples were determined. CONCLUSIONS: The integration strategy established here can discover and quantify the chemical markers for improving the quality control standard of natural monomer flavor of licorice. It is expected that the strategy will be valuable for further quality control of other natural monomer flavors in Chinese tobacco industry.

An Integral R-Banded Karyotype Analysis System of Bone Marrow Metaphases Based on Deep Learning.

CONTEXT.­: Conventional karyotype analysis, which provides comprehensive cytogenetic information, plays a significant role in the diagnosis and risk stratification of hematologic neoplasms. The main limitations of this approach include long turnaround time and laboriousness. Therefore, we developed an integral R-banded karyotype analysis system for bone marrow metaphases, based on deep learning. OBJECTIVE.­: To evaluate the performance of the internal models and the entire karyotype analysis system for R-banded bone marrow metaphase. DESIGN.­: A total of 4442 sets of R-banded normal bone marrow metaphases and karyograms were collected. Accordingly, 4 deep learning-based models for different analytic stages of karyotyping, including denoising, segmentation, classification, and polarity recognition, were developed and integrated as an R-banded bone marrow karyotype analysis system. Five-fold cross validation was performed on each model. The whole system was implemented by 2 strategies of automatic and semiautomatic workflows. A test set of 885 metaphases was used to assess the entire system. RESULTS.­: The denoising model achieved an intersection-over-union (IoU) of 99.20% and a Dice similarity coefficient (DSC) of 99.58% for metaphase acquisition. The segmentation model achieved an IoU of 91.95% and a DSC of 95.79% for chromosome segmentation. The accuracies of the segmentation, classification, and polarity recognition models were 96.77%, 98.77%, and 99.93%, respectively. The whole system achieved an accuracy of 93.33% with the automatic strategy and an accuracy of 99.06% with the semiautomatic strategy. CONCLUSIONS.­: The performance of both the internal models and the entire system is desirable. This deep learning-based karyotype analysis system has potential in clinical application.

U-Co Bimetallic-Organic Framework Showing a Helical 1D Pore Decorated by Abundant -CH3 Groups: Robust Nature under Acid, Base, and Water for High-Performance SO2 Removal.

Constructing robust adsorbents for SO2 removal remains a challenging issue. Herein, a U-Co bimetallic-organic framework, namely, ECUT-123, showing a helical 1D pore decorated by abundant -CH3 groups, enables ultrahigh stability under acid, base, and water. This merit further supports its big potential for the removal of trace SO2.

Incidence and Risk Factors of Postoperative Severe Discomfort After Elective Surgery Under General Anesthesia: A Prospective Observational Study.

PURPOSE: Patient comfort is an important concern in patients receiving surgery, but the seriousness of discomfort during recovery is unknown. We investigated the incidence of postoperative discomfort based on the Standardized Endpoints in Perioperative Medicine initiative for patient comfort, and identified the risk factors. DESIGN: This was a single-center prospective observational study. METHODS: We enrolled adult patients who underwent elective surgery under general anesthesia between July and December 2018 at West China Hospital of Sichuan University (ChiCTR1800017324). The primary outcome was the incidence of postoperative severe discomfort (PoSD), defined as occurring when a patient experienced a severe rating in two or more domains in the six domains in the Standardized Endpoints in Perioperative Medicine initiative on the same day, including rest pain, postoperative nausea, and vomiting, dissatisfaction of gastrointestinal recovery, dissatisfaction of mobilization, sleep disturbance, and recovery. A generalized estimated equation was constructed to find risk factors of PoSD. FINDINGS: In total, 440 patients completed the study. The incidence of PoSD was 28% on postoperative day (POD) 1, 13% on POD 2, 9% on POD 3, and 3.6% on both POD 5 and 7. The most common discomfort was serious sleep disturbance, ranging from 43% to 10% in the first week after surgery. Longer operative time (odds ratio [95% confidence interval]: 1.56 [1.19 to 2.05], P = .001), gastrointestinal surgery (5.03[2.08,12.17], P < .001), orthopaedic surgery (3.03 [1.35,6.79], P = .007), ear, nose, and throat (ENT) surgery (3.50 [1.22,10.02], P = .020) and postoperative complications (1.77 [1.03-3.04], P = .038) were significant risk factors of PoSD. CONCLUSIONS: The incidence of PoSD after elective surgery under general anesthesia is high. Sleep disturbance was the most common problem identified. Anesthesia providers and perianesthesia nurses may need to optimize anesthetic application, combine different anesthesia methods, improve perioperative management, and provide interventions to reduce and to treat discomfort after surgeries.

Robust metal-organic framework with multiple traps for trace Xe/Kr separation.

Direct separation of Xe and Kr from air or used nuclear fuel (UNF) off-gas by means of porous adsorbents is of industrial importance but is a very challenging task. In this work, we show a robust metal-organic framework (MOF), namely ECUT-60, which renders not only high chemical stability, but also unique structure with multiple traps. This leads to the ultrahigh Xe adsorption capacity, exceeding most reported porous materials. Impressively, this MOF also enables high selectivity of Xe over Kr, CO2, O2, and N2, leading to the high-performance separation for trace quantitites of Xe/Kr from a simulated UNF reprocessing off-gas. The separation capability has been demonstrated by using dynamic breakthrough experiments, giving the record Xe uptake up to 70.4 mmol/kg and the production of 19.7 mmol/kg pure Xe. Consequently, ECUT-60 has promising potential in direct production of Xe from UNF off-gas or air. The separation mechanism, as unveiled by theoretical calculation, is attributed to the multiple traps in ECUT-60 that affords rigid restrict for Xe atom via van der Waals force.

A near-infrared-II fluorescence anisotropy strategy for separation-free detection of adenosine triphosphate in complex media.

Fluorescence anisotropy (FA) has been widely applied for detecting and monitoring special targets in life sciences. However, matrix autofluorescence restricted its further application in complex biological samples. Herein, we report a near-infrared-II (NIR-II) FA strategy for detecting adenosine triphosphate (ATP) in human serum samples and breast cancer cell lysate, which employed NIR-II fluorescent Ag2Se quantum dots (QDs) as tags to reduce matrix autofluorescence effect and applied graphene oxide (GO) to enhance fluorescence anisotropy signals. In the presence of ATP, the recognition between NIR-II Ag2Se QDs labeled aptamer (QD-pDNA) and ATP led to the release of QD-pDNA from GO, resulting in the obvious decrease of FA values. ATP could be quantitatively detected in concentrations ranged from 3 nM to 2500 nM, with a detection limit down to 1.01 nM. This study showed that the developed NIR-II FA strategy could be applied for detecting targets in complex biological samples and had great potential for monitoring interactions between biomolecules in biomedical research.

Grafting functional groups in metal-organic frameworks for U(VI) sorption from aqueous solutions.

Nuclear power is becoming one of the major clean energies for its high efficiency and low load on the environment. Uranium is a key strategic resource for nuclear power. Uranium reclamation from aqueous systems is of great significance, not only in the usage of nuclear power but also for the remediation of nuclear leakage pollution. Recently, metal-organic frameworks (MOFs) with high porosity, regular pore structure and modifiable functional groups, have been considered as one of the most effective uranium adsorption materials. Specifically, the post-grafted functional groups possess strong affinity to uranium. This frontier summarizes the recent progresses on grafting functional groups in MOFs for U(vi) sorption from aqueous solutions. The adsorption performance, interaction mechanisms and the grafted functional groups are assessed in this study. Finally, personal perspectives on challenges and opportunities are discussed with the hope of supporting and providing some assistance to the designation of MOF-based U(vi) sorption materials.

Boosting Selective Adsorption of Xe over Kr by Double-Accessible Open-Metal Site in Metal-Organic Framework: Experimental and Theoretical Research.

Obtaining highly valuable Xe from air or other sources is highly important but still seriously restricted by its inherent inert nature and the great difficulty in separation from other inert gases, especially for Xe and Kr that show comparable size. In this work, we show both experimental and theoretical research of how to boost the selective adsorption of Xe over Kr by double-accessible open-metal site in metal-organic framework (MOF). The MOF, namely, UTSA-74, shows a high Xe uptake up to 2.7 mmol/g and a lower Kr uptake of 0.58 mmol/g at 298 K and 1 bar, leading to a high selectivity of 8.4. The effective Xe/Kr separation was further confirmed by both transient breakthrough simulation and experimental breakthrough. The separation mechanism, as unveiled by the grand canonical Monte Carlo simulation and dispersion-corrected density functional theory calculation, is due to the unique double-accessible open-metal site in UTSA-74 that affords stronger interaction toward Xe than Kr.

A robust Th-azole framework for highly efficient purification of C2H4 from a C2H4/C2H2/C2H6 mixture.

Separation of C2H4 from C2H4/C2H2/C2H6 mixture with high working capacity is still a challenging task. Herein, we deliberately design a Th-metal-organic framework (MOF) for highly efficient separation of C2H4 from a binary C2H6/C2H4 and ternary C2H4/C2H2/C2H6 mixture. The synthesized MOF Azole-Th-1 shows a UiO-66-type structure with fcu topology built on a Th6 secondary building unit and a tetrazole-based linker. Such noticeable structure, is connected by a N,O-donor ligand with high chemical stability. At 100 kPa and 298 K Azole-Th-1 performs excellent separation of C2H4 (purity > 99.9%) from not only a binary C2H6/C2H4 (1:9, v/v) mixture but also a ternary mixture of C2H6/C2H2/C2H4 (9:1:90, v/v/v), and the corresponding working capacity can reach up to 1.13 and 1.34 mmol g-1, respectively. The separation mechanism, as unveiled by the density functional theory calculation, is due to a stronger van der Waals interaction between ethane and the MOF skeleton.

Identification of a t(X;17)(q28;q21) generating a KANSL1-MTCP1 gene fusion leading to dysregulated expression of MTCP1 in acute myeloid leukemia.

Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28;q21) chromosomal rearrangement in a patient with acute monocytic leukemia. Using RNA-sequencing, we identified a KANSL1-MTCP1 and a KANSL1-CMC4 fusion gene. 5'-UTR sequences of the KANSL1 gene were found to become fused upstream of the coding sequence region of the MTCP1 and CMC4 genes, respectively, resulting in an aberrantly high expression of these genes. Functional studies revealed that overexpression of the MTCP1 gene induced an increased cell proliferation and partial blockage of cell differentiation, suggesting that the aberrant expression of MTCP1 is of critical importance in leukemogenesis.

Measuring propionyl-CoA carboxylase activity in phytohemagglutinin stimulated lymphocytes using high performance liquid chromatography.

BACKGROUND: Propionyl-CoA carboxylase (PCC) is a mitochondrial enzyme involved in the catabolism of several essential amino acids and odd chain fatty acids. Previous PCC assays have involved either a radiometric assay or have required mitochondria isolation and/or enzyme purification. METHODS: We developed an enzymatic method to analyze PCC activity in phytohemagglutinin (PHA) stimulated lymphocytes that involves high performance liquid chromatography. RESULTS: The method shows good linearity and sensitivity. PCC activity was unaffected even when lymphocytes were isolated and PHA stimulated after a whole blood sample had been stored at 4°C for 5days. This indicates that this method is suitable for analyzing samples from distant medical centers. The PCC activity of patients with propionic acidemia was found to be much lower than that of normal individuals and carriers. However, this PCC assay is significantly affected by the red blood cell contamination. In conclusion, this is a reliable method for performing PCC assays and only requires 0.5 to 1.0ml of whole blood from newborns. CONCLUSIONS: The PCC assay established in this study is useful for the confirmation of PA in individuals, and prenatal diagnosis and genetic counseling for the affected families.

Mutation Profile of the MUT Gene in Chinese Methylmalonic Aciduria Patients.

The mut-type methylmalonic aciduria (MMA, MIM 251000) is caused by a deficiency of mitochondrial methylmalonyl-CoA mutase (MCM, E.C. 5.4.99.2) activity, which results from defects in the MUT gene. To elucidate the mutation spectrum of the MUT gene in Chinese MMA patients, 13 exons of the MUT gene, including untranslated regions, were analyzed by PCR-based sequencing for 42 unrelated Chinese MMA patients. All the 42 patients were found to have at least one MUT mutation. A total of 41 mutations were identified. Of these mutations, 20 were novel ones, including one nonsense mutation (c.103C>T), 12 missense mutations (c.316A>C, c.424A>G, c.494A>G, c.554C>T, c.599T>C, c.919T>C, c.1009T>C, c.1061C>T, c.1141G>A, c.1208G>A, c.1267G>A, and c.1295A>C), one duplication (c.755dupA), three small deletions (c.398_399delGA, c.1046_1058del, and c.1835delG), two mutations that might affect mRNA splicing (c.754-1G>A and c.1084-10A>G), and one major deletion. Among the mutations identified, the c.1280G>A (15.5%), c.729_730insTT (10.7%), c.1106G>A (4.8%), c.1630_1631GG>TA (4.8%), and c.2080C>T (4.8%) accounted for 40% of the diseased alleles. The c.1280G>A and c.729_730insTT mutations were found to be the most frequent mutations in Southern and Northern Chinese, respectively. The results of microsatellite analysis suggest that the spread of c.729_730insTT among the Northern Chinese and of c.1280G>A and c.1630_1631GG>TA among the Southern Chinese may have undergone founder effects. This mutation analysis of the gene responsible for mut-type MMA will help to provide a molecular diagnostic aid for differential diagnosis of MMA and could be applied for carrier detection and prenatal diagnosis among Chinese family at risk of mut-type MMA.