Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm.

Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.

Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.

Genomic basis for RNA alterations in cancer.

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.

Flexible Anionic Groups-Activated Structure Dissymmetry for Strong Nonlinearity in Ln2 Ae3 MIV 3 S12 Family.

Structural dissymmetry and strong second-harmonic generation (SHG) responses are key conditions for nonlinear optical (NLO) crystals, and targeted combinatorial screening of suitable anionic groups has become extremely effective. Herein, optimal combination of flexible SnSn (n = 5, 6) groups and highly electropositive cations (lanthanides (Ln3+ ) and alkaline earth (Ae2+ : Sr, Ca) metals) affords the successful synthesis of 12 NLO thiostannates including Ln2 Sr3 Sn3 S12 (Pmc21 ) and Ln2 Ca3 Sn3 S12 (P-62m); whereas 17 rigid GeS4 or SiS4 tetrahedra-constructed Ln2 Ae3 Ge3 S12 and Ln2 Ae3 Si3 S12 crystallize in the centrosymmetric (CS) Pnma. This unprecedented CS to noncentrosymmetric (NCS) structural transformation (Pnma to P-62m to Pmc21 ) in the Ln2 Ae3 MIV 3 S12 family indicates that chemical substitution of the tetrahedral GeS4 /SiS4 units with SnSn breaks the original symmetry to form the requisite NCS structures. Remarkably, strong polarization anisotropy and hyperpolarizability of the Sn(4+) S5 unit afford huge performance improvement from the nonphase-matching (NPM) SHG response (1.4 × AgGaS2 and Δn = 0.008) of La2 Ca3 Sn3 S12 to the strong phase-matching (PM) SHG effect (3.0 × AgGaS2 and Δn = 0.086) of La2 Sr3 Sn3 S12 . Therefore, Sn(4+) S5 is proven to be a promising "NLO-active unit." This study verifies that the coupling of flexible SnSn building blocks into structures opens a feasible path for designing targeted NCS crystals with strong nonlinearity and optical anisotropy.

Influence of Cation-Size Effects of Alkaline Earth (Ae) Metals on Dimensionality and Optical Anisotropy Regulation in K4AeP2S8 Thiophosphates.

Cationic substitution demonstrates significant potential for regulating structural dimensionality and physicochemical performance owing to the cation-size effect. Leveraging this characteristic, this study synthesized a new family of K4AeP2S8 (Ae = alkaline earth elements: Mg, Ca, Sr, and Ba) thiophosphates, involving the substitution of Ae2+ cations. The synthesized compounds crystallized in distinct space groups, monoclinic P2/c (Ae = Mg) versus orthorhombic Ibam (Ae = Ca, Sr, and Ba), exhibiting intriguing dimensionality transformations from zero-dimensional (0D) [Mg2P4S16]8- clusters in K4MgP2S8 to 1D ∞[AeP2S8]4- chains in other K4AeP2S8 thiophosphates owing to the varying ionic radii of Ae2+ cations, Ae-S bond lengths, and coordination numbers of AeSn (Mg: n = 6 versus other: n = 8). Experimental investigations revealed that K4AeP2S8 thiophosphates featured wide optical bandgaps (3.37-3.64 eV), and their optical absorptions were predominantly influenced by the S 3p and P 3s orbitals, with negligible contributions from the K and Ae cations. Notably, within the K4AeP2S8 series, birefringence (Δn) increased from K4MgP2S8 (Δn = 0.034) to other K4AeP2S8 (Δn = 0.050-0.079) compounds, suggesting that infinite 1D chains more significantly influence Δn origins than 0D clusters, thus offering a feasible approach for enhancing optical anisotropy and exploring potential new birefringent materials.

Ultra-Broad-Band-Excitable Cu-Based Halide (C4H10N)4Cu4I8 with High Stability for LED Applications.

Currently, organic-inorganic hybrid cuprous-based halides are receiving substantial attention for their eco-friendliness, distinctive structures, and outstanding photophysical properties. Nevertheless, most of the reported cuprous-based halides demand deep ultraviolet excitation with a narrow excitation range that can meet the commercial requirement. Herein, zero-dimensional (0D) cuprous-based halide (C4H10N)4Cu4I8 single crystals (SCs) were synthesized, with an ultrabroad band excitation ranging 260-450 nm and a greenish-yellow emission band peaking at 560 nm. Excitingly, (C4H10N)4Cu4I8 also features a large Stokes shift of 300 nm, a high photoluminescence quantum yield (PLQY) of up to 84.66%, and a long lifetime of 137 µs. Furthermore, density functional theory calculations were performed to explore the relationship between structure and photophysical properties, and the photoluminescence performance of (C4H10N)4Cu4I8 originates from the electron interactions in [Cu2I4]2- clusters. Taking advantage of broad band excitation and excellent photoluminescent performances, a high luminescence characteristic UV-pumped light-emitting diode (LED) device with remarkable color stability was fabricated by employing the as-synthesized (C4H10N)4Cu4I8 SCs, which present the promising applications of low-dimensional cuprous-based halides in solid-state lighting.

Prognostic Value of Left Ventricular Global Longitudinal Strain for Major Adverse Cardiovascular Events in Patients with Aortic Valve Disease: A Meta-Analysis.

INTRODUCTION: Valvular heart disease is one of the most common heart diseases. It is characterized by abnormal function or structure of the heart valves. There may be no clinical symptoms in the early stages. Clinical symptoms of arrhythmia, heart failure, or thromboembolic events may occur in the late stages of the disease, such as palpitation after activities, breathing difficulties, fatigue, and so on. Aortic valve disease is a major part of valvular heart disease. The main treatment for aortic valve disease is valve replacement or repair surgery, but it is extremely risky. Therefore, a rigorous prognostic assessment is extremely important for patients with aortic valve disease. The global longitudinal strain is an index that describes the deformation capacity of myocardium. There is evidence that it provides a test for systolic dysfunction other than LVEF (left ventricular ejection fraction) and provides additional prognostic information. METHOD: Search literature published between 2010 and 2023 on relevant platforms and contain the following keywords: "Aortic valve disease," "Aortic stenosis," "Aortic regurgitation," and "longitudinal strain" or "strain." The data is then extracted and collated for analysis. RESULTS: A total of 15 articles were included. The total population involved in this study was 3,678 individuals. The absolute value of LVGLS was higher in the no-MACE group than in the MACE group in patients with aortic stenosis (Z = 8.10, p < 0.00001), and impaired LVGLS was a risk factor for MACE in patients with aortic stenosis (HR = 1.14, p < 0.00001, 95% CI: 1.08-1.20). There was also a correlation between impaired LVGLS and aortic valve surgery in patients with aortic valve disease (HR = 1.16, p < 0.0001, 95% CI: 1.08-1.25) or patients with aortic valve regurgitation (HR = 1.21, p = 0.0004, 95% CI: 1.09-1.34). We also found that impaired LVGLS had no significant association between LVGLS and mortality during the period of follow-up in patients with aortic valve stenosis (HR = 1.08, 95% CI: 0.94-1.25, p = 0.28), but it was associated with mortality in studies of prospective analyses (HR = 1.34, 95% CI: 1.02-1.75, p = 0.04). CONCLUSIONS: Impaired LVGLS correlates with major adverse cardiovascular events in patients with aortic valve disease, and it has predictive value for the prognosis of patients with aortic valve disease.

Directional region-based feature point matching algorithm based on SURF.

Feature point matching is one of the fundamental tasks in binocular vision. It directly affects the accuracy and quality of 3D reconstruction. This study proposes a directional region-based feature point matching algorithm based on the SURF algorithm to improve the accuracy of feature point matching. First, same-name points are selected as the matching reference points in the left and right images. Then, the SURF algorithm is used to extract feature points and construct the SURF feature point descriptors. During the matching process, the location relationship between the query feature point and the reference point in the left image is directed to determine the corresponding matching region in the right image. Then, the matching is completed within this region based on Euclidean distance. Finally, the grid-based motion statistics algorithm is used to eliminate mismatches. Experimental results show that the proposed algorithm can substantially improve the matching accuracy and the number of valid matched points, particularly in the presence of a large amount of noise and interference. It also exhibits good robustness and stability.

Catalytic Refining Lignin-derived Monomers: Seesaw Effect between Nanoparticle and Single-Atom Pt.

Pt automatically adsorbed on oxygen vacancy of TiO2 via an in-situ interfacial redox reaction, resulting in atomically dispersion of Pt on TiO2.In the upgrading of lignin-derived 4-propylguaiacol, single-atom catalyst (SAC) Pt/TiO2-H achieved a conversion of 96.9% and a demethoxylation selectivity of 93.3% under 3 MPa H2 at 250 °C for 3 h, markedly different from the performance of nanoparticle counterpart that gave deep deoxygenation selectivity over 99.0%. The high demethoxylation activity of SAC Pt/TiO2-H is mainly attributed to its weak hydrogen spillover capacity that suppressed the benzene ring hydrogenation and the deep deoxygenation. Additionally, SAC Pt/TiO2-H reduced the energy barrier of CAr-OCH3 bond cleavage and accordingly lowered the Gibbs free energy of the demethoxylation reaction. This facile method could fabricate single-atom Au, Pd, Ir, and Ru supported on TiO2-H, demonstrating the generality of this strategy for the establishment of a library of SACs. Moreover, SAC exhibited versatile capacity in demethoxylation of different lignin-derived monomers and high stability.This study showcases the superiority of atomically dispersed metal catalysts for selective demethoxylation reactions and proposes a renewable alternative to fossil-based 4-alkylphenols through upgrading of lignin-derived monomers.

d6versus d10, Which Is Better for Second Harmonic Generation Susceptibility? A Case Study of K2TGe3Ch8 (T = Fe, Cd; Ch = S, Se).

Two acentric chalcogenide compounds, K2CdGe3S8 and K2CdGe3Se8, were synthesized via conventional high-temperature solid-state reactions. The crystal structures of K2CdGe3S8 and K2CdGe3Se8 were accurately determined by single-crystal X-ray diffraction and crystallize in the K2FeGe3S8 structure type. K2CdGe3S8 is isostructural to K2FeGe3S8 with superior nonlinear optical properties. For the second harmonic generation (SHG) response, K2CdGe3S8 is 18× K2FeGe3S8 for samples of particle size of 38-55 µm. The superior nonlinear optical properties of K2CdGe3S8 over K2FeGe3S8 are mainly contributed by the chemical characteristics of Cd compared with Fe, which are elucidated by nonlinear optical property measurements, electronic structure calculations, and density functional theory calculations. The [CdS4] tetrahedra within K2CdGe3S8 exhibit a higher degree of distortion and larger volume compared to the [FeS4] tetrahedra in K2FeGe3S8. This study possesses a good platform to investigate how d-block elements contribute to the SHG response. The fully occupied d10-elements are better for SHG susceptibility than d6-elements in this study. K2CdGe3S8 is a good candidate as an infrared nonlinear optical material of high SHG response (2.1× AgGaS2, samples of particle size of 200-250 µm), type-I phase-matching capability, high laser damage threshold (6.2× AgGaS2), and good stability.

Noncentrosymmetric Na6Pb3P4S16 and Centrosymmetric K2MIIP2S6 (MII = Mg and Zn) Displaying Multiple Membered-Ring Configurations and Strong Optical Anisotropy.

Three thiophosphates including noncentrosymmetric Na6Pb3P4S16 and centrosymmetric K2MIIP2S6 (MII = Mg and Zn) were successfully synthesized in vacuum-sealed silica tubes. Note that interesting multiple six membered-rings (6-MRs) including 6-NaS6-MRs and 6-KSn-MRs (n = 6 and 7) formed by A+-centered polyhedra were discovered in the structures of title thiophosphates and these MR-composed three-dimensional (3D) tunnels show great possibility to facilitate the filling of various structural blocks (such as zero-dimensional (0D) Pb3S10 trimers or one-dimensional (1D) (MIISn)n chains). Na6Pb3P4S16 exhibits the strongest nonlinear optical (NLO) response (5.4 × AgGaS2) with phase-matching (PM) behavior among the known Pb-based PM NLO sulfides, which is much larger than that of Pb3P2S8 (3.5 × AgGaS2); it was verified that such large second harmonic generation (SHG) response in Na6Pb3P4S16 can be attributed to the huge contribution of stereochemically active PbS4 units based on the SHG-density and dipole-moment calculations. Moreover, title thiophosphates show large birefringences (Δn = 0.102-0.21), which indicates that incorporation of [P2S6] dimers or polarized PbS4 units into structures provides positive benefits for the onset of strong optical anisotropy.

Comprehensive evaluation of BRCA1/2 variant interpretation ability among laboratories in China.

High-quality interpretation of BRCA1/2 variants plays a critical role in the clinical practice of precision medicine. However, a comprehensive system to evaluate the quality and accuracy of variant interpretation has yet to be established. This study investigates the performance of an interpretation system in evaluating the capacities of BRCA1/2 interpretation among distinct laboratories in China. The evaluation system is based on a reference database that contains 750 different variants in BRCA1/2 Evaluation was performed among 41 laboratories in China. We classified their performance into five levels. Only level A was considered qualified. This level allows for a 0.3% error rate for clinical decision-related misinterpretation; 26 of 41 laboratories (63%) met the qualified standard, while 7 laboratories were at levels D and E, which indicated egregious mistakes and systemic problems in variant interpretation. Due to strict quality demands, the interpretation of several variants was amended, which largely influenced the quality rate. The number of qualified laboratories would decrease from 26 to 17 if those incorrect recommended interpretations were not corrected. This evaluation system provides a potential approach for standardisation of variant interpretation and lowers the discordance of variant interpretation between different laboratories. A well-designed interpretation ability evaluation is essential to evaluate the interpretation level of laboratories before they provide service in real-world clinical settings.

Metagenomic analysis reveals crosstalk between gut microbiota and glucose-lowering drugs targeting the gastrointestinal tract in Chinese patients with type 2 diabetes: a 6 month, two-arm randomised trial.

AIMS/HYPOTHESIS: The use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses. METHODS: This was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose (n=50) or vildagliptin (n=50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations. RESULTS: Ninety-two participants were analysed. After 6 months of acarbose (n=44) or vildagliptin (n=48) monotherapy, both groups achieved significant reductions in HbA1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre-post comparisons <0.05). Both arms showed drug-specific and shared changes in relative abundances of multiple gut microbial species and pathways, especially the common reductions in Bacteroidetes species. Three months and 6 months of acarbose-induced changes in microbial composition were highly similar in type 2 diabetes patients from the two independent studies. Vildagliptin treatment significantly enhanced fasting active glucagon-like peptide-1 (GLP-1) levels. Baseline gut microbiota, rather than baseline GLP-1 levels, were strongly associated with GLP-1 response to vildagliptin, and to a lesser extent with GLP-1 response to acarbose. CONCLUSIONS/INTERPRETATION: This study reveals common microbial responses in type 2 diabetes patients treated with two glucose-lowering drugs targeting the gut differently and acceptable performance of baseline gut microbiota in classifying individuals with different GLP-1 responses to vildagliptin. Our findings highlight bidirectional interactions between gut microbiota and glucose-lowering drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02999841 FUNDING: National Key Research and Development Project: 2016YFC1304901.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

Tumor heterogeneity assessed by sequencing and fluorescence in situ hybridization (FISH) data.

MOTIVATION: Computational reconstruction of clonal evolution in cancers has become a crucial tool for understanding how tumors initiate and progress and how this process varies across patients. The field still struggles, however, with special challenges of applying phylogenetic methods to cancers, such as the prevalence and importance of copy number alteration (CNA) and structural variation events in tumor evolution, which are difficult to profile accurately by prevailing sequencing methods in such a way that subsequent reconstruction by phylogenetic inference algorithms is accurate. RESULTS: In this work, we develop computational methods to combine sequencing with multiplex interphase fluorescence in situ hybridization to exploit the complementary advantages of each technology in inferring accurate models of clonal CNA evolution accounting for both focal changes and aneuploidy at whole-genome scales. By integrating such information in an integer linear programming framework, we demonstrate on simulated data that incorporation of FISH data substantially improves accurate inference of focal CNA and ploidy changes in clonal evolution from deconvolving bulk sequence data. Analysis of real glioblastoma data for which FISH, bulk sequence and single cell sequence are all available confirms the power of FISH to enhance accurate reconstruction of clonal copy number evolution in conjunction with bulk and optionally single-cell sequence data. AVAILABILITY AND IMPLEMENTATION: Source code is available on Github at https://github.com/CMUSchwartzLab/FISH_deconvolution. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

CqsA-introduced quorum sensing inhibits type VI secretion system 2 through an OpaR-dependent pathway in Vibrio parahaemolyticus.

The well-known food-borne pathogen Vibrio parahaemolyticus employs at least three quorum sensing signals to maintain its high environmental adaptability. V. parahaemolyticus CqsA, the synthase involved in 3-hydroxyundecan-4-one quorum sensing signal, introduces a quorum sensing network. The V. parahaemolyticus virulent factor type VI secretion system 2 (T6SS2), which is associated with adhesion to host cells, was previously reported to be regulated by a quorum sensing system. Herein, we set out to determine the role of CqsA-introduced quorum sensing (CIQS) in T6SS2-associated virulent regulation. Using a tandem mass tag (TMT)-based quantitative proteomics assay, 17 T6SS2 proteins were found having significantly higher abundances in the ΔcqsA strain than in the wild type strain. TMT proteomics assay results were confirmed by a parallel reaction-monitoring (PRM)-based proteomics assay. Two T6SS2 up-regulators, OpaR and CalR, were found under control of CIQS in the TMT proteomics assay, while OpaR was down-regulated and CalR was up-regulated by CIQS. Thus, it was hypothesized that CIQS would inhibit T6SS2 with an OpaR-dependent mechanism. Epistasis experiment with quantitative PCR was designed to analyze the role of OpaR in the process of CIQS inhibiting T6SS2 production. The mRNA levels of T6SS2 genes were up-regulated in the ΔcqsA strain while down-regulated in the ΔopaR strain and in the ΔcqsAΔopaR mutant, indicating that OpaR plays a predominant role in the regulation of T6SS2 by CIQS. Using a cell adhesion assay, we further found that the T6SS2-dependent adhesion activity of V. parahaemolyticus to Hela cells was also inhibited by CIQS and the inhibition was OpaR-dependent. In this study, we confirmed that V. parahaemolyticus CIQS inhibited T6SS2 through an OpaR-dependent pathway. It enriches the knowledge of how V. parahaemolyticus quorum sensing regulates its virulence.

Sex Differences and Temporal Trends in Hospitalization for Catheter Ablation of Nonvalvular Atrial Fibrillation: A Single-Center Experience for 15 Years.

Background: There exist sex differences in the clinical profile, management, and outcome of atrial fibrillation (AF). Catheter ablation of AF has become a first-line therapy and has markedly made headway over the recent decades. Little is known about sex differences and temporal trends in hospitalization for catheter ablation of AF in the real-world setting. Methods: We retrospectively retrieved medical records of patients at Beijing Anzhen Hospital between January 2005 and December 2019. The patients undergoing catheter ablation of AF were enrolled. Demographical and clinical data were compared between sexes. The temporal trends of sex differences were evaluated. Results: We identified 13502 male patients (66.8%) and 6713 female patients (33.2%). The number of patients undergoing AF ablation had remarkably increased over time, but no sex differences were observed (p=0.17). The median age of women was five years older than that of men (p < 0.001). The median time of in-hospital stay for the women decreased from 11 days to 4 days and for the men from 9 to 4 days. In-hospital mortality was 0.03% and 0.01% for women and men, respectively, with no significant difference between sexes. The women were more likely to have a comorbid diagnosis of hypertension and heart failure than men (p < 0.001). The CHA2DS2-VA score was higher in women than in men (1.64 vs. 1.28, p < 0.001). The temporal trend in the score increased in women from 1.17 to 1.81 (p < 0.001) and in men from 0.91 to 1.41 (p < 0.001). The percentage of patients with CHA2DS2-VA score ≥2 was higher in women than in men (49.8% vs. 35.8%, p < 0.001), and the temporal trend of this sex gap was nearly doubled (8.0% in 2005-2007 vs. 15.5% in 2017-2019, p=0.03). Conclusions: Safety of catheter ablation for AF was comparable in both sexes. In contrast, the women showed a higher CHA2DS2-VA score than men. The percentage of patients with CHA2DS2-VA score ≥2 increased more quickly in women than in men. Furthermore, sex-specific research is warranted to reduce this sex disparity.

Serum phosphopeptide profiling for colorectal cancer diagnosis using liquid chromatography-mass spectrometry.

RATIONALE: The identification and evaluation of novel biomarkers are essential to clinical diagnosis and prognosis of colorectal cancer (CRC). Serum phosphopeptides have been recognized as a potential signature pool for cancers; therefore, we aim to profile the expression of serum phosphopeptides and to evaluate their feasibility in CRC diagnosis. METHODS: We conducted the characterization and absolute quantification of endogenous phosphopeptides in sera using liquid chromatography-mass spectrometry analysis in combination with enrichment of phosphopeptides by ZrAs-Fe3 O4 @SiO2 nanoparticles and use of deuterium-labeled standards. Differentially expressed analysis of four phosphopeptides was performed, generating a two-phosphopeptide-based biomarker, LF3-4 , by logistic regression analysis, where LF3-4 is equal to (5.85 - 5.13 × [F3] - 3.57 × [F4]), and [F3] and [F4] are the concentration of phosphopeptides DpSGEGDFLAEGGGVR and ADpSGEGDFLAEGGGVR in sera, respectively. RESULTS: The LF3-4 values showed significant difference in CRC cases compared with controls, and yielded a specificity of 100%, leading to correct classification of 56 (93%) out of 60 CRC patients, including 12 (92.3%) of 13 CRC cases in stage I. Double-blind validation showed that 97.5% of CRC cases were discriminated accurately. CONCLUSIONS: The LF3-4 value was firstly verified to be a potential biomarker for CRC diagnosis, and may expand our view in underlying mechanisms for CRC.

Triphenylamine indanedione as an AIE-based molecular sensor with one-step facile synthesis toward viscosity detection of liquids.

Viscosity is one of the most important physical parameters in a liquid, noninvasive, and effective viscosity inspection method toward liquid safety that needs to be developed urgently. In this study, two kinds of novel molecular sensors, namely, DPBID and DPTMID, were strategically constructed by the triphenylamine indanedione derivates; the rotatable conjugate structure was utilized as the recognition site and fluorescence quencher. This couple of molecular sensors was synthesized in a one-step facile manner. DPTMID displayed longer emission wavelength and larger Stokes shift (195 nm in water, 138 nm in glycerol) with a narrower energy band. Moreover, DPTMID exhibited high selectivity, sensitivity, and significant fluorescence signal enhancement toward a higher viscous microenvironment. The molecular sensor displayed good photostability, selectivity, and universality in various commercial liquids and featured with typical aggregation-induced emission (AIE). With the aid of DPTMID, the thickening effects of liquid thickeners can be captured. More importantly, DPTMID was explored to visualize the viscosity fluctuations during the metamorphic stages of liquids, and it was found that the microenvironment viscosity level is closely related to the spoilage degree of liquids. The method with rapid detection, high sensitivity, cheap equipment, and fast results output toward food quality and safety inspection can be achieved through this study.