Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ...ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure.
Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed.
Serum FGF2 levels were higher in patients with heart failure (125.60 88.95, 183.40 pg/mL) than in those with non-heart-failure dyspnea (65.30 28.85, 78.95 pg/mL) and healthy controls (78.90 60.80, 87.20 pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide.
Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.
Kinetic‐scale magnetic dips (KSMDs), with a significant depression in magnetic field strength, and scale length close to and less than one proton gyroradius, were reported in the turbulent plasmas ...both in recent observation and numerical simulation studies. These KSMDs likely play important roles in energy conversion and dissipation. In this study, we present observations of the KSMDs that are labeled whistler mode waves, electrostatic solitary waves, and electron cyclotron waves in the magnetosheath. The observations suggest that electron temperature anisotropy or beams within KSMD structures provide free energy to generate these waves. In addition, the occurrence rates of the waves are higher in the center of the magnetic dips than at their edges, implying that the KSMDs might be the origin of various kinds of waves. We suggest that the KSMDs could provide favorable conditions for the generation of waves and transfer energy to the waves in turbulent magnetosheath plasmas.
Plain Language Summary
The Earth's magnetosheath is a turbulent plasma environment where energy conversion, particle acceleration, and mass and momentum transport take place. Many of these key processes involve kinetic‐scale physics. However, in‐depth studies from previous missions are limited by their lower spacecraft data resolution. The recent Magnetospheric Multiscale (MMS) mission provides us with a large amount of high‐temporal cadence data for studying kinetic‐scale physics in the magnetosheath. In this study, we report whistler mode waves, electrostatic solitary waves and electron cyclotron waves within kinetic‐scale magnetic dips (KSMDs) that can be generated in the turbulent magnetosheath. These waves could be excited by electron temperature anisotropy or beams. As is well known, plasma waves are important processes in converting energy, accelerating and scattering electrons and ions, and modifying the distributions of charged particles. If plasma instabilities develop within the KSMDs, the resulting waves could absorb free energy from plasma particles and may propagate out of the KSMDs. Thus, our discoveries could significantly advance the understanding of energy conversion and dissipation for kinetic‐scale turbulence. This study provides a new reference not only for observations in space physics but also for related basic plasma theories and numerical simulations.
Key Points
MMS observations reveal KSMDs coupled with whistler mode waves, electrostatic solitary waves, and electron cyclotron waves
These waves are excited by different plasma distributions, and the ESWs could affect the electron distributions in kinetic scale
Statistical results indicate that the KSMDs in the magnetosheath are a possible origin for various kinds of waves
Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile ...as a liquid biopsy medium in patients with BTC.
Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes.
Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis.
We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.
•This is the first study to compare somatic mutation profiling in tumor tissues, bile and plasma samples in BTC patients.•Our findings demonstrated that bile cfDNA outperformed plasma cfDNA in detecting somatic mutations.•Bile cfDNA might be a feasible liquid biopsy medium for BTC diagnosis.
The midline pattern of sternal ossification characteristic of the Cretaceous enantiornithine birds is unique among the Ornithodira, the group containing birds, nonavian dinosaurs and pterosaurs. This ...has been suggested to indicate that Enantiornithes is not the sister group of Ornithuromorpha, the clade that includes living birds and their close relatives, which would imply rampant convergence in many nonsternal features between enantiornithines and ornithuromorphs. However, detailed comparisons reveal greater similarity between neornithine (i.e. crown group bird) and enantiornithine modes of sternal ossification than previously recognized. Furthermore, a new subadult enantiornithine specimen demonstrates that sternal ossification followed a more typically ornithodiran pattern in basal members of the clade. This new specimen, referable to the Pengornithidae, indicates that the unique ossification pattern observed in other juvenile enantiornithines is derived within Enantiornithes. A similar but clearly distinct pattern appears to have evolved in parallel in the ornithuromorph lineage. The atypical mode of sternal ossification in some derived enantiornithines should be regarded as an autapomorphic condition rather than an indication that enantiornithines are not close relatives of ornithuromorphs. Based on what is known about molecular mechanisms for morphogenesis and the possible selective advantages, the parallel shifts to midline ossification that took place in derived enantiornithines and living neognathous birds appear to have been related to the development of a large ventral keel, which is only present in ornithuromorphs and enantiornithines. Midline ossification can serve to medially reinforce the sternum at a relatively early ontogenetic stage, which would have been especially beneficial during the protracted development of the superprecocial Cretaceous enantiornithines.
A full-length cDNA encoding a general odorant binding protein 2 (GOBP2) was cloned from the antennae of the rice striped stem borer, Chilo suppressalis (Lepidoptera: Pyralidae), by the combination of ...reverse transcription PCR (RT-PCR) and rapid amplification of cDNA ends PCR (RACE-PCR). The cDNA contains a 489 bp open reading frame, which encodes a 162 amino acid protein, termed as Ch. suppressalis GOBP2 (CsupGOBP2). CsupGOBP2 is similar in the number of amino acids and protein sequence to GOBP2s in other species of Lepidoptera. RT-PCR results showed that CsupGOBP2 mRNA was highly expressed in the adult antennae of both females and males, as was CsupGOBP2 protein as revealed by Western blot analysis. CsupGOBP2 expressed in Escherichia coli was purified by affinity chromatography, refolding and gel filtration from the inclusion body. Fluorescence emission spectra and competitive binding assays by using N-phenyl-1-naphthylamine as first binding ligand and odorants as potential competitors revealed that the CsupGOBP2 protein has significant affinity to cis-11-hexadecenal (Z11-16:Ald), the main component of Ch. suppressalis pheromone and to laurinaldehyd and benzaldehyde, two general plant volatile aldehydes.
In protein–ligand binding, only a few residues contribute significantly to the ligand binding. Quantitative characterization of binding free energies of specific residues in protein–ligand binding is ...extremely useful in our understanding of drug resistance and rational drug design. In this paper, we present an alanine scanning approach combined with an efficient interaction entropy method to compute residue-specific protein–ligand binding free energies in protein–drug binding. In the current approach, the entropic components in the free energies of all residues binding to the ligand are explicitly computed from just a single trajectory MD simulation by using the interaction entropy method. In this approach the entropic contribution to binding free energy is determined from fluctuations of individual residue–ligand interaction energies contained in the MD trajectory. The calculated residue-specific binding free energies give relative values between those for ligand binding to the wild type protein and those to the mutants when specific results mutated to alanine. Computational study for the binding of two classes of drugs (first and second generation drugs) to target protein ALK and its mutant was performed. Important or hot spot residues with large contributions to the total binding energy are quantitatively characterized and the mutation effect for the loss of binding affinity for the first generation drug is explained. Finally, it is very interesting to note that the sum of those individual residue-specific binding free energies are in quite good agreement with the experimentally measured total binding free energies for this protein–ligand system.
Microbial metabolism plays a key role in regulating the biogeochemical cycle of forest ecosystems, but the mechanisms driving microbial growth are not well understood. Here, we synthesized 689 ...measurements on soil microbial biomass carbon (Cmic) and nitrogen (Nmic) and related parameters from 207 independent studies published up to November 2014 across China's forest ecosystems. Our objectives were to (1) examine patterns in Cmic, Nmic, and microbial quotient (i.e., Cmic / Csoil and Nmic / Nsoil rates) by climate zones and management regimes for these forests; and (2) identify the factors driving the variability in the Cmic, Nmic, and microbial quotient. There was a large variability in Cmic (390.2 mg kg−1), Nmic (60.1 mg kg−1, Cmic : Nmic ratio (8.25), Cmic / Csoil rate (1.92 %), and Nmic / Nsoil rate (3.43 %) across China's forests. The natural forests had significantly greater Cmic (514.1 mg kg−1 vs. 281.8 mg kg−1) and Nmic (82.6 mg kg−1 vs. 39.0 mg kg−1) than the planted forests, but had less Cmic : Nmic ratio (7.3 vs. 9.2) and Cmic / Csoil rate (1.7 % vs. 2.1 %). Soil resources and climate together explained 24.4–40.7 % of these variations. The Cmic : Nmic ratio declined slightly with Csoil : Nsoil ratio, and changed with latitude, mean annual temperature and precipitation, suggesting a plasticity of microbial carbon-nitrogen stoichiometry. The Cmic / Csoil rate decreased with Csoil : Nsoil ratio, whereas the Nmic / Nsoil rate increased with Csoil : Nsoil ratio; the former was influenced more by soil resources than by climate, whereas the latter was influenced more by climate. These results suggest that soil microbial assimilation of carbon and nitrogen are jointly driven by soil resources and climate, but may be regulated by different mechanisms.
The major histocompatibility complex (MHC) can recognize and bind to external peptides to generate effective immune responses by presenting the peptides to T cells. Therefore, understanding the ...binding modes of peptide-MHC complexes (pMHC) and predicting the binding affinity of pMHCs play a crucial role in the rational design of peptide vaccines. In this study, we employed molecular dynamics (MD) simulations and free energy calculations with an Alanine Scanning with Generalized Born and Interaction Entropy (ASGBIE) method to investigate the protein-peptide interaction between HLA-A*02:01 and the G9
peptide derived from the melanoma antigen gp100. The energy contribution of individual residue was calculated using alanine scanning, and hotspots on both the MHC and the peptides were identified. Our study shows that the pMHC binding is dominated by the van der Waals interactions. Furthermore, we optimized the ASGBIE method, achieving a Pearson correlation coefficient of 0.91 between predicted and experimental binding affinity for mutated antigens. This represents a significant improvement over the conventional MM/GBSA method, which yields a Pearson correlation coefficient of 0.22. The computational protocol developed in this study can be applied to the computational screening of antigens for the MHC1 as well as other protein-peptide binding systems.
We study the process e^{+}e^{-}→Λ_{c}^{+}Λover ¯_{c}^{-} at twelve center-of-mass energies from 4.6119 to 4.9509 GeV using data samples collected by the BESIII detector at the BEPCII collider. The ...Born cross sections and effective form factors (|G_{eff}|) are determined with unprecedented precision after combining the single and double-tag methods based on the decay process Λ_{c}^{+}→pK^{-}π^{+}. Flat cross sections around 4.63 GeV are obtained and no indication of the resonant structure Y(4630), as reported by Belle, is found. In addition, no oscillatory behavior is discerned in the |G_{eff}| energy dependence of Λ_{c}^{+}, in contrast to what is seen for the proton and neutron cases. Analyzing the cross section together with the polar-angle distribution of the Λ_{c}^{+} baryon at each energy point, the moduli of electric and magnetic form factors (|G_{E}| and |G_{M}|) are extracted and separated. For the first time, the energy dependence of the form factor ratio |G_{E}/G_{M}| is observed, which can be well described by an oscillatory function.
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