Comprehensive metabolome characterization and comparison between two sources of Dragon's blood by integrating liquid chromatography/mass spectrometry and chemometrics.

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.

Natural stable calcium isotope ratios: a new gold standard for bone balance?

Bone calcium balance is the net gain, loss, or equilibrium of calcium moving to and from bone, which reflects bone balance. There are currently no clinically available tools for measuring real-time bone balance. In this issue, Shroff et al. demonstrate the use of natural stable calcium isotope ratios as a novel biomarker of bone balance in children with chronic kidney disease on dialysis that is highly repeatable and associated with radiological and biochemical markers of bone metabolism.

Determination of Picogram-per-Gram Concentrations of 231Pa and 230Th in Sediments by Melt Quenching and Laser Ablation Mass Spectrometry.

Uranium, thorium, and protactinium radionuclides in marine sediments are important proxies for understanding the earth's environmental evolution. Conventional solution-based methods, which typically involve isotope spike preparation, concentrated acid sample digestion, column chemistry, and mass spectrometry, allow precise but time-consuming and costly measurements of these nuclide concentrations (i.e., 230Th and 231Pa). In this work, we have established an efficient method for 230Th and 231Pa measurement of marine sediments down to the picogram-per-gram level without purification and enrichment. Our method first transforms a small amount of thermally decomposed sediments (∼0.1-0.2 g) to homogeneous silicate glass using a melt quenching technique and then analyzes the glass with laser ablation multicollector inductively coupled plasma-mass spectrometry. Standard sample bracketing with isotope-spike-calibrated glass standards prepared in this study was used to correct for instrumental fractionation during measurement. It is demonstrated that our method can accurately determine the U-Th-Pa concentrations of typical marine sediments in the late Pleistocene with precision of a few percent. Compared with the conventional solution-based methods, the turnover time of sample preparation and measurement with our established protocol is greatly reduced, facilitating future application of U-series radionuclides in reconstructing oceanic processes at high temporal and spatial resolution.

Geochemistry and Cosmochemistry of Potassium Stable Isotopes.

Stable potassium isotopes are one of the emerging non-traditional isotope systems enabled in recent years by the advance of Multi-Collector Inductively-Coupled-Plasma Mass-Spectrometry (MC-ICP-MS). In this review, we first summarize the geochemical and cosmochemical properties of K, its major reservoirs, and the analytical methods of K isotopes. Following this, we review recent literature on K isotope applications in the fields of geochemistry and cosmochemistry. Geochemically, K is a highly incompatible lithophile element, and a highly soluble, biophile element. The isotopic fractionation of K is relatively small during magmatic processes such as partial melting and fractional crystallization, whereas during low-temperature and biological processes fractionation is considerably larger. This resolvable fractionation has made K isotopes promising tracers for a variety of Earth and environmental processes, including chemical weathering, low-temperature alteration of igneous rocks, reverse weathering, and the recycling of sediments into the mantle during subduction. Sorption and interactions of aqueous K with different clay minerals during cation exchange and clay formation are likely to be of fundamental significance in generating much of the K isotope variability seen in samples from the Earth surface and samples carrying recycled surface materials from the deep Earth. The magnitude of this fractionation is process- and mineral-dependent. Comprehensive quantification of pertinent K isotope fractionation factors is currently lacking and urgently needed. Significant fractionation during biological activities, such as plant uptake, demonstrates the potential utility of K isotopes in the study of the nutrient cycle and its relation to the climate and various ecosystems, enabling new and largely unexplored avenues for future research. Of significant importance to the cosmochemistry community, K is a moderately volatile element with large variations in K/U ratio observed among chondrites and planetary materials. As this indicates different degrees of volatile depletion, it has become a fundamental chemical signature of both chondritic and planetary bodies. This volatile depletion has been attributed to various processes such as solar nebula condensation, mixing of volatile-rich and -poor reservoirs, planetary accretional volatilization via impacts, and/or magma ocean degassing. While K isotopes have the potential to distinguish these different processes, the current results are still highly debated. A good correlation between the K isotope compositions of four differentiated bodies (Earth, Mars, Moon, and Vesta) and their masses suggests a ubiquitous volatile depletion mechanism during the formation of the terrestrial planets. It is still unknown whether any of the K isotopic variation among chondrites and differentiated bodies can be attributed to inherited signatures of mass-independent isotopic anomalies.

Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Dendritic Cell-Derived IL-6 Production and Th17 Differentiation.

IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)-derived cytokines play pivotal roles in promoting the differentiation of naive CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules blocking the key cytokines produced by DCs will be beneficial in MS. In this article, we report that betaine treatment ameliorates MS pathogenesis by inhibiting DC-derived IL-6 production and Th17 differentiation. Using experimental autoimmune encephalomyelitis, a widely used mouse model of MS, we found that, compared with the vehicle-treated group, betaine-treated mice exhibited less severe experimental autoimmune encephalomyelitis symptoms, including lower clinical scores, reduced leukocyte infiltration, and less extensive demyelination in the CNS. Moreover, a significantly lower percentage of Th17 cells, one of the major pathogenic effector cells in MS progression, was observed in the peripheral immune system and in the CNS. Interestingly, in the in vitro Th17-differentiation assay, no significant change in Th17 cells was observed between the vehicle- and betaine-treated groups, whereas in the in vitro DC culture experiment, betaine treatment significantly decreased DC-derived IL-6 production. In the DC-T cell coculture experiment, a significantly decreased Th17 differentiation was observed upon betaine treatment. All of these data demonstrated that betaine inhibited Th17 differentiation indirectly by reducing IL-6 production by DCs. In brief, our findings demonstrated the pivotal roles of betaine in modulating MS pathogenesis and suggested that it may serve as a potential novel drug candidate for the treatment of MS.

eIF3b regulates the cell proliferation and apoptosis processes in chronic myelogenous leukemia cell lines via regulating the expression of C3G.

OBJECTIVE: To investigate the functions of eIF3b in chronic myelogenous leukemia (CML). METHODS: The expression of eIF3b was inhibited by transfecting aspecifically designed shRNA into the CML cell lines of TK-6 and K562. The CCK8 assay was conducted to determine cell viability, and flow cytometry was used to examine the change in the cell cycle and cell apoptosis. RNAsequencing was applied to screen the candidate targets of eIF3b to identify the underlying mechanisms of eIF3b.An in vivo tumour xenograft mouse model was established by injecting shRNA transfected cells into the NCG mice. The tumour size and body weight of mice were monitored every other day. The mice were sacrificed 2 weeks after the tumour cell injection. The expression of eIF3b and target genes in the tumour tissues were determined by immunohistochemical staining and Western blotting. RESULTS: The group with inhibited expression of eIF3b led to about 50% lower cell viability compared with that of the control group (P < 0.05). Flow cytometry suggested that the percentage of increase in apoptotic cells was eight times higher than those in control group for TK-6 and K562 cells (P < 0.05). However, the difference between the cell amounts in the S phase for the experiment and control groups was not significant. After RNAsequencing and further validation via qPCR, C3G was screened as the potential target of eIF3b involved in the cell proliferation and apoptosis of CML cell lines. Subsequent in vivo analysis proved that the inhibition of eIF3b suppressed tumour formation and decreased C3G expression, thereby indicating that C3G was the potential target of eIF3b. CONCLUSION: eIF3b is correlated with the cell proliferation and cell apoptosis of CML. Moreover, eIF3b regulation most probably occurs via regulating the expression of C3G.

Explaining deep learning-based representations of resting state functional connectivity data: focusing on interpreting nonlinear patterns in autism spectrum disorder.

Background: Resting state Functional Magnetic Resonance Imaging fMRI (rs-fMRI) has been used extensively to study brain function in psychiatric disorders, yielding insights into brain organization. However, the high dimensionality of the rs-fMRI data presents significant challenges for data analysis. Variational autoencoders (VAEs), a type of neural network, have been instrumental in extracting low-dimensional latent representations of resting state functional connectivity (rsFC) patterns, thereby addressing the complex nonlinear structure of rs-fMRI data. Despite these advances, interpreting these latent representations remains a challenge. This paper aims to address this gap by developing explainable VAE models and testing their utility using rs-fMRI data in autism spectrum disorder (ASD). Methods: One-thousand one hundred and fifty participants (601 healthy controls [HC] and 549 patients with ASD) were included in the analysis. RsFC correlation matrices were extracted from the preprocessed rs-fMRI data using the Power atlas, which includes 264 regions of interest (ROIs). Then VAEs were trained in an unsupervised manner. Lastly, we introduce our latent contribution scores to explain the relationship between estimated representations and the original rs-fMRI brain measures. Results: We quantified the latent contribution scores for both the ASD and HC groups at the network level. We found that both ASD and HC groups share the top network connectivitives contributing to all estimated latent components. For example, latent 0 was driven by rsFC within ventral attention network (VAN) in both the ASD and HC. However, we found significant differences in the latent contribution scores between the ASD and HC groups within the VAN for latent 0 and the sensory/somatomotor network for latent 2. Conclusion: This study introduced latent contribution scores to interpret nonlinear patterns identified by VAEs. These scores effectively capture changes in each observed rsFC feature as the estimated latent representation changes, enabling an explainable deep learning model that better understands the underlying neural mechanisms of ASD.

Bioinspired High-Strength Borate Cross-Linked Microfibrillated Cellulose Composite Laminate with Self-Extinguishing Flame Retardance and Superhydrophobicity for Self-Cleaning.

The cross-linking of borates enhances the intercellular structural connection, resulting in the creation of a mechanically superior structural material composed of lignocellulose and borate. This is accomplished by employing a mechanical pretreatment procedure and a binder-free hot-pressing method. Nevertheless, these materials frequently encounter constraints in humid environments, making it challenging to simultaneously achieve the desired performance objectives. Here, the prepressed bulk of microfibrillated cellulose is modified and subjected to hot pressing, while ensuring that the enhanced physical and mechanical properties of lignocellulosic recombinant materials are maintained. This modified material is termed the microfibrillated cellulose composite laminate (MCCL). These findings indicate that the application of compression, shear, and friction forces during hot-pressing results in the formation of a compact laminated structure using pine lignocellulose. The self-cleaning MCCL exhibits significantly improved mechanical properties compared with untreated lignocellulose materials (ULM). Specifically, the flexural strength (MOR), modulus of elasticity (MOE), and internal bonding strength (IB) of self-cleaning MCCL are found to be 5 times, 2.5 times, and 4.1 times higher, respectively, than those of ULM. This improvement in the pine lignocellulose can be attributed to the enhanced layering and branching that occurs during mechanical milling. This results in a higher proportion of ester and hydrogen bonds, as well as an increased exposure of hydroxyl groups. As a result, the modified MCCL exhibits self-cleaning properties, as evidenced by its surface water contact angle (WCA) of 152°. The rolling/jumping water droplets, which contain pollutants, effectively remove graphite powder from the surface, leaving it clean. Moreover, MCCL demonstrates exceptional dimensional stability and flame-retardant self-extinguishing properties, making it highly promising as a structural material in engineering technology.

The genome of okra (Abelmoschus esculentus) provides insights into its genome evolution and high nutrient content.

Okra (Abelmoschus esculentus) is an important vegetable crop with high nutritional value. However, the mechanism underlying its high nutrient content remains poorly understood. Here, we present a chromosome-scale genome of okra with a size of 1.19 Gb. Comparative genomics analysis revealed the phylogenetic status of A. esculentus, as well as whole-genome duplication (WGD) events that have occurred widely across the Malvaceae species. We found that okra has experienced three additional WGDs compared with the diploid cotton Gossypium raimondii, resulting in a large chromosome number (2n = 130). After three WGDs, okra has undergone extensive genomic deletions and retained substantial numbers of genes related to secondary metabolite biosynthesis and environmental adaptation, resulting in significant differences between okra and G. raimondii in the gene families related to cellulose synthesis. Combining transcriptomic and metabolomic analysis, we revealed the relationship between gene expression and metabolite content change across different okra developmental stages. Furthermore, the sinapic acid/S-lignin biosynthesis-related gene families have experienced remarkable expansion in okra, and the expression of key enzymes involved in the sinapic acid/S-lignin biosynthesis pathway vary greatly across developmental periods, which partially explains the differences in metabolite content across the different stages. Our study gains insights into the comprehensive evolutionary history of Malvaceae species and the genetic basis that underlies the nutrient content changes in okra, which will facilitate the functional study and genetic improvement of okra varieties.

Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures.

Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40-60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.

High Fluorescence Rate of Thermally Activated Delayed Fluorescence Emitters for Efficient and Stable Blue OLEDs.

A lack of an efficient and stable blue device is a critical factor restricting the development of organic light-emitting diode (OLED) technology that is currently expected to be overcome by employing thermally activated delayed fluorescence (TADF). Here, we investigate the TADF and electroluminescence (EL) performance of six carbazole/triphenyltriazine derivatives in different hosts. A good linearity between lg(LT50/kF2) and the EL emission wavelength is found, where LT50 is the half-life of the devices and kF is the fluorescence rate of the emitters, suggesting the dominance of the singlet exciton energy and lifetime in device stability. An indolylcarbazole/triphenyltriazine derivative (ICz-TRZ) with the capability to suppress solid-state solvation exhibits blue-shifted emission and an increased kF (1.5 × 108 s-1) in comparison to the control emitters in doped films. ICz-TRZ-based devices achieve a maximum external quantum efficiency (EQE) of 18% and an EQE of 5.5% at a very high luminance of 7 × 104 cd/m2. Ignoring the poor electrochemical stability of ICz-TRZ, the device offers an LT50 approaching 100 h under an initial luminance of 1000 cd/m2 and CIE coordinates of (0.14, 0.19). The findings in this work suggest that computer-aided design of high kF TADF emitters can be an approach to realize efficient and stable blue OLEDs.

A Novel Metal-Organic Framework Composite, MIL-101(Cr)@MIP, as an Efficient Sorbent in Solid-Phase Extraction Coupling with HPLC for Tribenuron-Methyl Determination.

A highly efficient and selective method based on core-shell molecularly imprinted polymers (MIL@MIP) and high performance liquid chromatography (HPLC) was developed and firstly used for the trace analysis of tribenuron-methyl (TBM) in complicated matrices. The MIL@MIP was prepared by surface molecular-imprinting technique, specially using MIL-101 as core, TBM as template molecule, methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as cross-linker, and azobisisobutyronitrile (AIBN) as initiator. The resulting MIL@MIP showed high affinity, recognition specificity, fast mass transfer rate, and efficient adsorption performance towards TBM with the adsorption capacity reaching up to 3.217 mg/g. It also showed high cross-selectivity for TBM among its six kinds of chemical structure analogues. Furthermore, using the MIL@MIP as solid-phase extraction (SPE) materials, the recoveries of TBM determined by HPLC were 84.6-92.3%, 93.3-106.7%, and 88.9-93.3% in the spiked river water, soil, and soybean samples, respectively, with the limit of detection of 0.3 ng/L, 1.5 ng/kg, and 1.5 ng/kg, accordingly. It was proved that the developed HPLC-MISPE method was fast, accurate, and sensitive for detecting the trace TBM in river water, soil, and soybean samples.

Signature of quantum Griffiths singularity state in a layered quasi-one-dimensional superconductor.

Quantum Griffiths singularity was theoretically proposed to interpret the phenomenon of divergent dynamical exponent in quantum phase transitions. It has been discovered experimentally in three-dimensional (3D) magnetic metal systems and two-dimensional (2D) superconductors. But, whether this state exists in lower dimensional systems remains elusive. Here, we report the signature of quantum Griffiths singularity state in quasi-one-dimensional (1D) Ta2PdS5 nanowires. The superconducting critical field shows a strong anisotropic behavior and a violation of the Pauli limit in a parallel magnetic field configuration. Current-voltage measurements exhibit hysteresis loops and a series of multiple voltage steps in transition to the normal state, indicating a quasi-1D nature of the superconductivity. Surprisingly, the nanowire undergoes a superconductor-metal transition when the magnetic field increases. Upon approaching the zero-temperature quantum critical point, the system uncovers the signature of the quantum Griffiths singularity state arising from enhanced quenched disorders, where the dynamical critical exponent becomes diverging rather than being constant.

Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening.

Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs' cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1ß during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy.