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.

Intranasal delivery of small extracellular vesicles reduces the progress of amyotrophic lateral sclerosis and the overactivation of complement-coagulation cascade and NF-ĸB signaling in SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell-derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.

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.