FT-ICR MS Spectral Improvement of Dissolved Organic Matter by the Absorption Mode: A Comparison of the Electrospray Ionization in Positive-Ion and Negative-Ion Modes.

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in the absorption mode has a superior performance over the conventional magnitude mode. However, this improved performance for the analysis of dissolved organic matter (DOM) in negative-ion and positive-ion modes of electrospray ionization [ESI(-) and ESI(+), respectively] remains unknown. This study systemically compared the improved performance by the absorption mode for DOM FT-ICR MS spectra acquired with the low-field and high-field magnet instruments between two charge modes. The absorption mode enhanced the resolution and signal-to-noise ratio values of DOM peaks with factors of 1.88-1.94 and 1.60-1.72, respectively. The significantly higher improvement of mass resolution for the ESI(+) mode than that for the ESI(-) mode could resolve the extensive occurrence of mass doublets in the ESI(+) mode, yielding some formulas exclusively identified in the ESI(+) mode. The findings of this study have systemically demonstrated the superiority of the absorption mode in improving the spectra quality during the routine FT-ICR MS postdata analysis and highlighted its great potential in characterizing the molecular composition of DOM using the FT-ICR MS technique in both ESI(-) and ESI(+) modes.

Mesenchymal stromal cells and their small extracellular vesicles in allergic diseases: From immunomodulation to therapy.

Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.

Interpretable Machine Learning and Reactomics Assisted Isotopically Labeled FT-ICR-MS for Exploring the Reactivity and Transformation of Natural Organic Matter during Ultraviolet Photolysis.

Isotopically labeled FT-ICR-MS combined with multiple post-analyses, including interpretable machine learning (IML) and a paired mass distance (PMD) network, was employed to unravel the reactivity and transformation of natural organic matter (NOM) during ultraviolet (UV) irradiation. FT-ICR-MS analysis was used to assign formulas, which were classified on the basis of their molecular compositions and structural categories. Isotope (deuterium, D) labeling was utilized to unequivocally determine the photochemical products and examine the development of OD radical-mediated NOM transformation. With regard to the reactive molecular formulas, CHOS formulas exhibited the highest reactivity (86.5% of precursors disappeared) followed by CHON (53.4%) and CHO (24.6%) formulas. With regard to structural categories, the degree of reactivity decreased in the following order: tannins > condensed aromatics > lignin/CRAMs. The IML algorithm demonstrated that the crucial features governing the reactivity of formulas were the molecular weight, DBE-O, NOSC, and the presence of heteroatoms (i.e., N and S), suggesting that the large and unsaturated compounds containing S and N are more prone to photodegradation. The reactomics approach using the PMD network further indicated that 11 specific molecular formulas in the CHOS and CHO class served as hubs, implying a higher photoreactivity and participation in a range of transformations. The isotope labeling analyses also found that, among the reactions observed, hydroxylation (i.e., +OD) is dominant for lignin/CRAMs and condensed aromatics, and formulas containing ≤10 D atoms were developed. Overall, this study, by adopting rigorous and interpretable techniques, could provide in-depth insights into the molecular-level dynamics of NOM under UV irradiation.

Hidden Role of Organic Matter in the Immobilization and Transformation of Iodine on Fe-OM Associations.

The biogeochemical processes of iodine are typically coupled with organic matter (OM) and the dynamic transformation of iron (Fe) minerals in aquifer systems, which are further regulated by the association of OM with Fe minerals. However, the roles of OM in the mobility of iodine on Fe-OM associations remain poorly understood. Based on batch adsorption experiments and subsequent solid-phase characterization, we delved into the immobilization and transformation of iodate and iodide on Fe-OM associations with different C/Fe ratios under anaerobic conditions. The results indicated that the Fe-OM associations with a higher C/Fe ratio (=1) exhibited greater capacity for immobilizing iodine (∼60-80% for iodate), which was attributed to the higher affinity of iodine to OM and the significantly decreased extent of Fe(II)-catalyzed transformation caused by associated OM. The organic compounds abundant in oxygen with high unsaturation were more preferentially associated with ferrihydrite than those with poor oxygen and low unsaturation; thus, the associated OM was capable of binding with 28.1-45.4% of reactive iodine. At comparable C/Fe ratios, the mobilization of iodine and aromatic organic compounds was more susceptible in the adsorption complexes compared to the coprecipitates. These new findings contribute to a deeper understanding of iodine cycling that is controlled by Fe-OM associations in anaerobic environments.

Activated Carbon Application Simultaneously Alleviates Paddy Soil Arsenic Mobilization and Carbon Emission by Decreasing Porewater Dissolved Organic Matter.

Flooding of paddy fields during the rice growing season enhances arsenic (As) mobilization and greenhouse gas (e.g., methane) emissions. In this study, an adsorbent for dissolved organic matter (DOM), namely, activated carbon (AC), was applied to an arsenic-contaminated paddy soil. The capacity for simultaneously alleviating soil carbon emissions and As accumulation in rice grains was explored. Soil microcosm incubations and 2-year pot experimental results indicated that AC amendment significantly decreased porewater DOM, Fe(III) reduction/Fe2+ release, and As release. More importantly, soil carbon dioxide and methane emissions were mitigated in anoxic microcosm incubations. Porewater DOM of pot experiments mainly consisted of humic-like fluorophores with a molecular structure of lignins and tannins, which could mediate microbial reduction of Fe(III) (oxyhydr)oxides. Soil microcosm incubation experiments cospiking with a carbon source and AC further consolidated that DOM electron shuttling and microbial carbon source functions were crucial for soil Fe(III) reduction, thus driving paddy soil As release and carbon emission. Additionally, the application of AC alleviated rice grain dimethylarsenate accumulation over 2 years. Our results highlight the importance of microbial extracellular electron transfer in driving paddy soil anaerobic respiration and decreasing porewater DOM in simultaneously remediating As contamination and mitigating methane emission in paddy fields.

Enrichment of Geogenic Organoiodine Compounds in Alluvial-Lacustrine Aquifers: Molecular Constraints by Organic Matter.

Organoiodine compounds (OICs) are the dominant iodine species in groundwater systems. However, molecular mechanisms underlying the geochemical formation of geogenic OICs-contaminated groundwater remain unclear. Based upon multitarget field monitoring in combination with ultrahigh-resolution molecular characterization of organic components for alluvial-lacustrine aquifers, we identified a total of 939 OICs in groundwater under reducing and circumneutral pH conditions. In comparison to those in water-soluble organic matter (WSOM) in sediments, the OICs in dissolved organic matter (DOM) in groundwater typically contain fewer polycyclic aromatics and polyphenol compounds but more highly unsaturated compounds. Consequently, there were two major sources of geogenic OICs in groundwater: the migration of the OICs from aquifer sediments and abiotic reduction of iodate coupled with DOM iodination under reducing conditions. DOM iodination occurs primarily through the incorporation of reactive iodine that is generated by iodate reduction into highly unsaturated compounds, preferably containing hydrophilic functional groups as binding sites. It leads to elevation of the concentration of the OICs up to 183 µg/L in groundwater. This research provides new insights into the constraints of DOM molecular composition on the mobilization and enrichment of OICs in alluvial-lacustrine aquifers and thus improves our understanding of the genesis of geogenic iodine-contaminated groundwater systems.

ERK/CREB and p38 MAPK/MMP14 Signaling Pathway Influences Spermatogenesis through Regulating the Expression of Junctional Proteins in Eriocheir sinensis Testis.

The hemolymph-testis barrier (HTB) is a reproduction barrier in Crustacea, guaranteeing the safe and smooth process of spermatogenesis, which is similar to the blood-testis barrier (BTB) in mammals. The MAPK signaling pathway plays an essential role in spermatogenesis and maintenance of the BTB. However, only a few studies have focused on the influence of MAPK on crustacean reproduction. In the present study, we knocked down and inhibited MAPK in Eriocheir sinensis. Increased defects in spermatogenesis were observed, concurrently with a damaged HTB. Further research revealed that es-MMP14 functions downstream of ERK and p38 MAPK and degrades junctional proteins (Pinin and ZO-1); es-CREB functions in the ERK cascade as a transcription factor of ZO-1. In addition, when es-MMP14 and es-CREB were deleted, the defects in HTB and spermatogenesis aligned with abnormalities in the MAPK. However, JNK impacts the integrity of the HTB by changing the distribution of intercellular junctions. In summary, the MAPK signaling pathway maintains HTB integrity and spermatogenesis through es-MMP14 and es-CREB, which provides insights into the evolution of gene function during barrier evolution.

[Effects of different exercise modes on neuromuscular junction and metabolism of skeletal muscle-related proteins in aging rats].

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.

Degradation behaviors of Nabumetone and its metabolite during UV/monochloramine process: Experimental and theoretical study.

This study investigated degradation behaviors of a nonsteroidal anti-inflammatory drug Nabumetone (NMT) and its major metabolite 6-methoxy-2-naphthylacetic acid (MNA) in the coupling process of ultraviolet and monochloramine (UV/NH2Cl). The second-order rate constants of the contaminants reacting with reactive radicals (HO•, Cl•, Cl2•⁻, and CO3•⁻) were determined by laser flash photolysis experiments. HO• and Cl• contributed predominantly with 52.3% and 21.7% for NMT degradation and 60.8% and 22.3% for MNA degradation. The presence of chlorides retarded the degradation of NMT, while promoted the destruction of MNA, which was ascribed to the photosensitization effects of MNA under UV irradiation. Density functional theory (DFT) calculations revealed that radical adduct formation (RAF) was dominant pathway for both HO• and Cl• reacting with the contaminants, and hydrogen atom transfer (HAT) preferred to occur on side chains of NMT and MNA. NMT reacted with NO2• through single electron transfer (SET) with the second-order rate constant calculated to be 5.35 × 107 (mol/L)-1 sec-1, and the contribution of NO2• was predicted to be 13.0% of the total rate constant of NMT in pure water, which indicated that NO2• played a non-negligible role in the degradation of NMT. The acute toxicity and developmental toxicity of NMT were enhanced after UV/NH2Cl treatment, while those of MNA were alleviated. The transformation products of both NMT and MNA exhibited higher mutagenicity than their parent compounds. This study provides a deep understanding of the mechanism of radical degradation of NMT and MNA in the treatment of UV/NH2Cl.

Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice.

Although neuronal Toll-like receptors (TLRs) (e.g., TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive. Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone-ether-water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA (mRNA) expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, TNF-α, and IFN-γ were inhibited in TLR2-/- mice, while CXCL2, IL-31, and IL-6 were inhibited in TLR7-/- mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, and TNF-α were inhibited in TLR2-/- mice, while CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, and TNF-α were inhibited in TLR7-/- mice. Incubation with Staphylococcus aureus (S. aureus) peptidoglycan (PGN-SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142-3p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C-X-C Motif Chemokine Receptor 1/2 and high mobility group box protein 1 dose-dependently attenuated acute and chronic itch in mice. Together, these results indicate that keratinocyte TLR2 and TLR7 signaling pathways are distinctly involved in the pathogenesis of chronic itch.

Development of a Gaussian-Based Alignment Algorithm for the Ultrahigh-Resolution Mass Spectra of Dissolved Organic Matter.

The alignment of ultrahigh-resolution mass spectra (UHR-MS) is critical to inspect the presence of unique and common peaks across multiple UHR-MS spectra. However, few attempts have been conducted to develop an automated alignment method. In this study, a novel automated alignment algorithm, namely, FTMSCombine, that follows a Gaussian distribution of mass errors was developed and then integrated with existing FTMSCalibrate and TRFu algorithms to establish an open-source analysis platform, namely, FTMSAnalysis, for the UHR-MS analysis of the dissolved organic matter. The developed FTMSCombine was capable of automatically aligning peaks across different UHR-MS spectra by averaging the m/z values of each peak cluster, although the alignment should be restricted to Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) spectra collected by instruments under similar conditions. The FTMSCombine exhibited an insignificant difference in the reproducibility of chemical formulae but significantly higher mass accuracy than the ICBM-OCEAN. In addition to improving the overall mass accuracy of the whole UHR-MS dataset, the FTMSCombine could effectively exclude scatters or noise peaks using an optional rule that restricts peaks (continuously) detected in at least a certain number of spectra in the UHR-MS spectra dataset. The successfully established FTMSAnalysis (freely available in the Supporting Information of this study) is of great potential in automatically analyzing UHR-MS spectra for dissolved organic matter (DOM) and will largely facilitate the elucidation of DOM chemodivesity by UHR-MS techniques including FTICR-MS.

Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis.

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases.

Plastome phylogenomics and morphological traits analyses provide new insights into the phylogenetic position, species delimitation and speciation of Triplostegia (Caprifoliaceae).

BACKGROUND: The genus Triplostegia contains two recognized species, T. glandulifera and T. grandiflora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. RESULTS: Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandiflora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentified as T. glandulifera, but differs in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96 Ma, and within it T. glandulifera diverged 7.94 Ma. Triplostegia grandiflora and sp. A diverged 1.05 Ma, perhaps in response to Quaternary climate fluctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. CONCLUSIONS: Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identified that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegia.

mTORC1/rpS6 and mTORC2/PKC regulate spermatogenesis through Arp3-mediated actin microfilament organization in Eriocheir sinensis.

Mammalian target of rapamycin (mTOR) is a crucial signaling protein regulating a range of cellular events. Numerous studies have reported that the mTOR pathway is related to spermatogenesis in mammals. However, its functions and underlying mechanisms in crustaceans remain largely unknown. mTOR exists as two multimeric functional complexes termed mTOR complex 1 (mTORC1) and mTORC2. Herein, we first cloned ribosomal protein S6 (rpS6, a downstream molecule of mTORC1) and protein kinase C (PKC, a downstream effector of mTORC2) from the testis of Eriocheir sinensis. The dynamic localization of rpS6 and PKC suggested that both proteins may be essential for spermatogenesis. rpS6/PKC knockdown and Torin1 treatment led to defects in spermatogenesis, including germ cell loss, retention of mature sperm and empty lumen formation. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was disrupted in the rpS6/PKC knockdown and Torin1 treatment groups, accompanied by changing in expression and distribution of junction proteins. Further study demonstrated that these findings may result from the disorganization of filamentous actin (F-actin) networks, which were mediated by the expression of actin-related protein 3 (Arp3) rather than epidermal growth factor receptor pathway substrate 8 (Eps8). In summary, our study illustrated that mTORC1/rpS6 and mTORC2/PKC regulated spermatogenesis via Arp3-mediated actin microfilament organization in E. sinensis.

Dissecting the promotional effect of zinc on cadmium translocation from roots to shoots in rice.

It is often expected that Zn decreases Cd accumulation in plants due to competition for the same transporters. Here, we found that increasing Zn supply markedly increased the root-to-shoot translocation of Cd in rice. RNA sequencing showed that high Zn up-regulated expression of genes involved in glutathione biosynthesis and metabolism and the Zn/Cd transporter gene OsHMA2, but down-regulated expression of genes related to Zn uptake. Knockout of the iron or Zn transporter genes OsIRT1, OsIRT2, or OsZIP9 did not affect the Zn promotional effect on Cd translocation. Knockout of the manganese/Cd transporter gene OsNRAMP5 greatly reduced Cd uptake but did not affect the Zn promotional effect. Variation in the tonoplast transporter gene OsHMA3 affected Cd translocation but did not change the Zn promotional effect. Knockout of the Zn/Cd transporter gene OsHMA2 not only decreased Cd and Zn translocation, but also abolished the Zn promotional effect. Increased expression of OsHMA2 under high Zn conditions supports the hypothesis that this transporter participates in the promotional effect of Zn on Cd translocation. The results also show that OsIRT1, OsIRT2, and OsZIP9 made only small contributions to Cd uptake under low Zn conditions but not under high Zn conditions, whereas the dominant role of OsNRAMP5 in Cd uptake diminished under low Zn conditions.

Dilational Rheology of Extended Surfactants at the Air/Water and Oil/Water Interfaces: Effect of Propylene Oxide Group Numbers.

In this paper, the interfacial properties of extended surfactants with different oxypropylene (PO) groups were comprehensively investigated by using interfacial dilational rheology. The differences in molecular orientation, spatial configuration, and relaxation process were compared at the gas-water interface and oil-water interface. The influences of the PO groups on the interface viscoelasticity were analyzed, providing important theoretical support for the wide application of extended surfactants. Experimental results show that the lower number of PO groups in extended surfactants does not cause differences in their presence states on the interface; however, once it increases, the longer PO segment will spiral up in the direction perpendicular to the interface, forming a spatial configuration like a thin cylinder. Compared with air, the PO group has better solubility in the oil phase. The chain segment can still maintain a helical extension from the beginning to the end as a result. However, the upper layer of the thin cylinder will collapse to a certain extent at the surface. Moreover, the orientation of the hydrophobic side has a dynamic process of "tilting to upright" with the increase of adsorption amount or in response to interfacial dilation and compression. The increase of PO number or the insertion of oil molecules has little effect on dilational modulus, and the interfacial film strength is generally relatively low. That is to say, the better emulsifying and solubilizing ability of PO-containing extended surfactants may be more attributed to the matching steric effect at interface or better packing action in bulk phase than to higher film strength.

Subtractionless compressed-sensing-accelerated whole-body MR angiography using two-point Dixon fat suppression with single-pass half-reduced contrast dose: feasibility study and initial experience.

PURPOSE: To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). MATERIALS AND METHODS: This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. RESULTS: The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P < 0.001). In total, 1776 and 1406 arterial segments in the CS-WBMRA and conventional-WBMRA group were evaluated. Qualitative image scores for 7 (of 15) vessel segments in the CS-WMBRA group had statistically significantly increased values compared to those of the conventional-WBMRA groups (P < 0.05). Scores from the other 8 segments showed similar image quality (P > 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P < 0.001), while overall apparent CNRs were not significantly different in these two groups (CS vs conventional: 107.13 ± 72.323 vs 161.24 ± 118.64; P > 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and < 30 s for the conventional WBMRA group, respectively. The contrast agent dose used in the CS-WBMRA protocol was reduced by half compared to conventional-WBMRA protocol (18.7 ± 3.5 ml vs 37.2 ± 5.4 ml, P = 0.008). CONCLUSION: The CS-WBMRA protocol provides excellent image quality and sufficient diagnostic accuracy for whole-body arterial disease, with relatively faster workflow and half-dose reduction of contrast agent, which has greater potential in clinical practice compared with conventional-WBMRA.

Complementary Elucidation of the Molecular Characteristics of Groundwater Dissolved Organic Matter Using Ultrahigh-Resolution Mass Spectrometry Coupled with Negative- and Positive-Ion Electrospray Ionization.

The formula assignment of the Fourier transform ion cyclotron resonance mass spectrometry coupled with positive-ion electrospray ionization [ESI(+)-FT-ICR MS] is challenging because of the extensive occurrence of adducts. However, there is a paucity of automated formula assignment methods for ESI(+)-FT-ICR MS spectra. The novel automated formula assignment algorithm for ESI(+)-FT-ICR MS spectra developed herein has been applied to elucidate the composition of dissolved organic matter (DOM) in groundwater during air-induced ferrous [Fe(II)] oxidation. The ESI(+)-FT-ICR MS spectra of groundwater DOM were profoundly impacted by [M + Na]+ adducts and, to a lesser extent, [M + K]+ adducts. Oxygen-poor and N-containing compounds were frequently detected when the FT-ICR MS was operated in the ESI(+) mode, while the components with higher carbon oxidation states were preferentially ionized in the negative-ion electrospray ionization [ESI(-)] mode. Values for the difference between double-bond equivalents and the number of oxygen atoms from -13 to 13 are proposed for the formula assignment of the ESI(+)-FT-ICR MS spectra of aquatic DOM. Furthermore, for the first time, the Fe(II)-mediated formation of highly toxic organic iodine species was reported in groundwater rich in Fe(II), iodide, and DOM. The results of this study not only shed light on the further algorithm development for comprehensive characterization of DOM by ESI(-)-FT-ICR MS and ESI(+)-FT-ICR MS but also highlight the importance of appropriate treatment of specific groundwater prior to use.

Copper Safeguards Dissolved Organic Matter from Sunlight-Driven Photooxidation.

Sunlight plays a crucial role in the transformation of dissolved organic matter (DOM) and the associated carbon cycle in aquatic environments. This study demonstrates that the presence of nanomolar concentrations of copper (Cu) significantly decreases the rate of photobleaching and the rate of loss of electron-donating moieties of three selected types of DOM (including both terrestrial and microbially derived DOM) under simulated sunlight irradiation. Employing Fourier transform ion cyclotron resonance mass spectrometry, we further confirm that Cu selectively inhibits the photooxidation of lignin- and tannin-like phenolic moieties present within the DOM, in agreement with the reported inhibitory impact of Cu on the photooxidation of phenolic compounds. On the basis of the inhibitory impact of Cu on the DOM photobleaching rate, we calculate the contribution of phenolic moieties to DOM photobleaching to be at least 29-55% in the wavelength range of 220-460 nm. The inhibition of loss of electrons from DOM during irradiation in the presence of Cu is also explained quantitatively by developing a mathematical model describing hydrogen peroxide (a proxy measure of loss of electrons from DOM) formation on DOM irradiation in the absence and presence of Cu. Overall, this study advances our understanding of DOM transformation in natural sunlit waters.

DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain.

Circular RNAs (ciRNAs) are emerging as new players in the regulation of gene expression. However, how ciRNAs are involved in neuropathic pain is poorly understood. Here, we identify the nervous-tissue-specific ciRNA-Fmn1 and report that changes in ciRNA-Fmn1 expression in spinal cord dorsal horn neurons play a key role in neuropathic pain after nerve injury. ciRNA-Fmn1 was significantly downregulated in ipsilateral dorsal horn neurons after peripheral nerve injury, at least in part because of a decrease in DNA helicase 9 (DHX9), which regulates production of ciRNA-Fmn1 by binding to DNA-tandem repeats. Blocking ciRNA-Fmn1 downregulation reversed nerve-injury-induced reductions in both the binding of ciRNA-Fmn1 to the ubiquitin ligase UBR5 and the level of ubiquitination of albumin (ALB), thereby abrogating the nerve-injury-induced increase of ALB expression in the dorsal horn and attenuating the associated pain hypersensitivities. Conversely, mimicking downregulation of ciRNA-Fmn1 in naïve mice reduced the UBR5-controlled ubiquitination of ALB, leading to increased expression of ALB in the dorsal horn and induction of neuropathic-pain-like behaviors in naïve mice. Thus, ciRNA-Fmn1 downregulation caused by changes in binding of DHX9 to DNA-tandem repeats contributes to the genesis of neuropathic pain by negatively modulating UBR5-controlled ALB expression in the dorsal horn.