The interplay of soil physicochemical properties, methanogenic diversity, and abundance governs methane production potential in paddy soil subjected to multi-decadal straw incorporation.

Straw incorporation holds significant promise for enhancing soil fertility and mitigating air pollution stemming from straw burning. However, this practice concurrently elevates the production and emission of methane (CH4) from paddy ecosystems. Despite its environmental impact, the precise mechanisms behind the heightened CH4 production resulting from long-term straw incorporation remain elusive. In a 32-year field experiment featuring three fertilization treatments (CFS-chemical fertilizer with wheat straw, CF-chemical fertilizer, and CK-unamended), we investigated the impact of abiotic (soil physicochemical properties) and biotic (methanogenic abundance, diversity, and community composition) factors on CH4 production in paddy fields. Results revealed a significantly higher CH4 production potential under CFS treatment compared to CF and CK treatments. The partial least squares path model revealed that soil physicochemical properties (path coefficient = 0.61), methanogenic diversity (path coefficient = -0.43), and methanogenic abundance (path coefficient = 0.29) collectively determined CH4 production potential, explaining 77% of the variance. Enhanced soil organic carbon content and water content, resulting from straw incorporation, emerged as pivotal factors positively correlated with CH4 production potential. Under CFS treatment, lower Shannon index of methanogens, compared to CF and CK treatments, was attributed to increased Methanosarcina. Notably, the Shannon index and relative abundance of Methanosarcina exhibited negative and positive correlations with CH4 production potential, respectively. Methanogenic abundance, bolstered by straw incorporation, significantly amplified overall potential. This comprehensive analysis underscores the joint influence of abiotic and biotic factors in regulating CH4 production potential during multi-decadal straw incorporation.

Vertical distribution of Candidatus Methylomirabilis and Methanoperedens in agricultural soils.

Candidatus Methylomirabilis-related bacteria conduct anaerobic oxidation of methane (AOM) coupling with NO2- reduction, and Candidatus Methanoperedens-related archaea perform AOM coupling with reduction of diverse electron acceptors, including NO3-, Fe (III), Mn (IV) and SO42-. Application of nitrogen fertilization favors the growth of these methanotrophs in agricultural fields. Here, we explored the vertical variations in community structure and abundance of the two groups of methanotrophs in a nitrogen-rich vegetable field via using illumina MiSeq sequencing and quantitative PCR. The retrieved Methylomirabilis-related sequences had 91.12%-97.32% identity to the genomes of known Methylomirabilis species, and Methanoperedens-related sequences showed 85.49%-97.48% identity to the genomes of known Methanoperedens species which are capable of conducting AOM coupling with reduction of NO3- or Fe (III). The Methanoperedens-related archaeal diversity was significantly higher than Methylomirabilis-related bacteria, with totally 74 and 16 operational taxonomic units, respectively. In contrast, no significant difference in abundance between the bacteria (9.19 × 103-3.83 × 105 copies g-1 dry soil) and the archaea (1.55 × 104-3.24 × 105 copies g-1 dry soil) was observed. Furthermore, the abundance of both groups of methanotrophs exhibited a strong vertical variation, which peaked at 30-40 and 20-30 cm layers, respectively. Soil water content and pH were the key factors influencing Methylomirabilis-related bacterial diversity and abundance, respectively. For the Methanoperedens-related archaea, both soil pH and ammonium content contributed significantly to the changes of these archaeal diversity and abundance. Overall, we provide the first insights into the vertical distribution and regulation of Methylomirabilis-related bacteria and Methanoperedens-related archaea in vegetable soils. KEY POINTS: • The archaeal diversity was significantly higher than bacterial. • There was no significant difference in the abundance between bacteria and archaea. • The abundance of bacteria and archaea peaked at 30-40 and 20-30 cm, respectively.

The methodological quality assessment of systematic reviews/meta-analyses of chronic prostatitis/chronic pelvic pain syndrome using AMSTAR2.

BACKGROUND: This study aimed to assess the methodological quality of the systematic reviews/meta-analyses (SRs/MAs) of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using A Measurement Tool to Assess systematic Reviews (AMSTAR2) and to explore the potential influencing factors. METHODS: PubMed, EMBASE and Cochrane Library databases were searched for relevant studies. AMSTAR2 was used for evaluating the methodological quality of eligible SRs/MAs. Differences between methodological characteristics of SRs/MAs were compared using chi-square tests. The intra-class correlation coefficient (ICC) was used to assess reviewer agreement in the pre-experiment. Multivariate regression analysis was used to identify potential factors affecting methodological quality. RESULTS: A total of 45 SRs/MAs were included. After AMSTAR2 evaluation, only two (4.4%) of 45 SRs/MAs were moderate, three (6.7%) were rated as low quality, and the remainder 40 (88.9%) were rated as critically low quality. Among the 16 items of AMSTAR2, item 3 and item 10 had the poorest adherence. Item 4 received the most significant number of "Partial Yes" responses. Univariable analysis indicated that there were significant differences in methodological quality in SRs between different continents (P = 0.027) as well as between preregistered SRs and those that were not (P = 0.004). However, in multivariate analysis, there was no significant association between methodological quality and the following research characteristics: publication year, continent, whether reporting followed Preferred Reporting Items for Systematic Reviews (PRISMA), preregistration, funding support, randomized controlled trials (RCT) enrollment, whether SR was published in the Cochrane Database of Systematic Reviews (CDSR), and whether with meta-analysis. Additionally, subgroup analysis based on interventional SRs/MAs showed that continent was independently associated with the methodological quality of SRs/MAs of CP/CPPS via univariable and multivariate analysis. CONCLUSIONS: Our study demonstrates that the methodological quality of SRs/MAs of CP/CPPS was generally poor. SRs/MAs of CP/CPPS should adopt the AMSTAR2 to enhance their methodological quality.

Role and regulation of anaerobic methane oxidation catalyzed by NC10 bacteria and ANME-2d archaea in various ecosystems.

Freshwater wetlands, paddy fields, inland aquatic ecosystems and coastal wetlands are recognized as important sources of atmospheric methane (CH4). Currently, increasing evidence shows the potential importance of the anaerobic oxidation of methane (AOM) mediated by NC10 bacteria and a novel cluster of anaerobic methanotrophic archaea (ANME)-ANME-2d in mitigating CH4 emissions from different ecosystems. To better understand the role of NC10 bacteria and ANME-2d archaea in CH4 emission reduction, the current review systematically summarizes different AOM processes and the functional microorganisms involved in freshwater wetlands, paddy fields, inland aquatic ecosystems and coastal wetlands. NC10 bacteria are widely present in these ecosystems, and the nitrite-dependent AOM is identified as an important CH4 sink and induces nitrogen loss. Nitrite- and nitrate-dependent AOM co-occur in the environment, and they are mainly affected by soil/sediment inorganic nitrogen and organic carbon contents. Furthermore, salinity is another key factor regulating the two AOM processes in coastal wetlands. In addition, ANME-2d archaea have the great potential to couple AOM to the reduction of iron (III), manganese (IV), sulfate, and even humics in different ecosystems. However, the study on the environmental distribution of ANME-2d archaea and their role in CH4 mitigation in environments is insufficient. In this study, we propose several directions for future research on the different AOM processes and respective functional microorganisms.

Effects of abrupt and gradual increase of atmospheric CO2 concentration on methanotrophs in paddy fields.

The simulation of abrupt atmospheric CO2 increase is a common way to examine the response of soil methanotrophs to future climate change. However, atmosphere is undergoing a gradual CO2 increase, and it is unknown whether the previously reported response of methanotrophs to abrupt CO2 increase can well represent their response to the gradual increase. To improve the understanding of the effect of elevated CO2 (eCO2) on methanotrophs in paddy ecosystems, the methane oxidation potential and communities of methanotrophs were examined via open top chambers under the three following CO2 treatments: an ambient CO2 concentration (AC); an abrupt CO2 increase by 200 ppm above AC (AI); a gradual CO2 increase by 40 ppm each year until 200 ppm above AC (GI). Relative to AC treatment, AI and GI treatments significantly (p < 0.05) increased the methane oxidation rate by 43.8% and 36.7%, respectively, during rice growth period. Furthermore, the abundance of pmoA genes was significantly (p < 0.05) increased by 62.4% and 32.5%, respectively, under AI and GI treatments. However, there were no significant variations in oxidation rate or gene abundance between the two eCO2 treatments. In addition, no obvious change of overall community composition of methanotrophs was observed among treatments, while the proportions of Methylosarcina and Methylocystis significantly (p < 0.05) changed. Taken together, our results indicate similar response of methanotrophs to abrupt and gradual CO2 increase, although the magnitude of response under gradual increase was smaller and the abrupt increase may somewhat overestimate the response.

Response of potential activity, abundance and community composition of nitrite-dependent anaerobic methanotrophs to long-term fertilization in paddy soils.

The process of nitrite-dependent anaerobic methane oxidation (n-damo) catalysed by Candidatus Methylomirabilis oxyfera (M. oxyfera)-like bacteria is a novel pathway in regulating methane (CH4 ) emissions from paddy fields. Nitrogen fertilization is essential to improve rice yields and soil fertility; however, its effect on the n-damo process is largely unknown. Here, the potential n-damo activity, abundance and community composition of M. oxyfera-like bacteria were investigated in paddy fields under three long-term (32 years) fertilization treatments, i.e. unfertilized control (CK), chemical fertilization (NPK) and straw incorporation with chemical fertilization (SNPK). Relative to the CK, both NPK and SNPK treatments significantly (p < 0.05) increased the potential n-damo activity (88%-110%) and the abundance (52%-105%) of M. oxyfera-like bacteria. The variation of soil organic carbon (OrgC) content and inorganic nitrogen content caused by the input of chemical fertilizers and straw returning were identified as the key factors affecting the potential n-damo activity and the abundance of M. oxyfera-like bacteria. However, the community composition and diversity of M. oxyfera-like bacteria did not change significantly by the input of fertilizers. Overall, our results provide the first evidence that long-term fertilization greatly stimulates the n-damo process, indicating its active role in controlling CH4 emissions from paddy fields.

Novel Gas Diffusion Cloth Bioanodes for High-Performance Methane-Powered Microbial Fuel Cells.

Microbial fuel cells (MFCs) are a promising technology that converts chemical energy into electricity. However, up to now only few MFCs have been powered by gas fuels, such as methane, and their limited performance is still challenged by the low solubility and bioavailability of gases. Here, we developed a gas diffusion cloth (GDC) anode to significantly enhance the performance of methane-powered MFCs. The GDC anode was constructed by simply coating waterproof GORE-TEX cloth with conductive carbon cloth in one step. After biofilm enrichment, the GDC anodes obtained a methane-dependent current up to 1130.2 mA m-2, which was 165.2 times higher than conventional carbon cloth (CC) anodes. Moreover, MFCs equipped with GDC anodes generated a maximum power density of 419.5 mW m-2. Illumina high-throughput sequencing revealed that the GDC anode biofilm was dominated mainly by Geobacter, in contrast with the most abundant Methanobacterium in planktonic cells. It is hypothesized that Methanobacterium reversed the methanogenesis process by transferring electrons to the anodes, and Geobacter generated electricity via the intermediates (e.g., acetate) of anaerobic methane oxidation. Overall, this work provides an effective route in preparing facile and cost-effective anodes for high-performance methane MFCs.

Identification and molecular characterization of tissue-preferred rice genes and their upstream regularly sequences on a genome-wide level.

BACKGROUND: Gene upstream regularly sequences (URSs) can be used as one of the tools to annotate the biological functions of corresponding genes. In addition, tissue-preferred URSs are frequently used to drive the transgene expression exclusively in targeted tissues during plant transgenesis. Although many rice URSs have been molecularly characterized, it is still necessary and valuable to identify URSs that will benefit plant transformation and aid in analyzing gene function. RESULTS: In this study, we identified and characterized root-, seed-, leaf-, and panicle-preferred genes on a genome-wide level in rice. Subsequently, their expression patterns were confirmed through quantitative real-time RT-PCR (qRT-PCR) by randomly selecting 9candidate tissue-preferred genes. In addition, 5 tissue-preferred URSs were characterized by investigating the URS::GUS transgenic plants. Of these URS::GUS analyses, the transgenic plants harboring LOC_Os03g11350 URS::GUS construct showed the GUS activity only in young pollen. In contrast, when LOC_Os10g22450 URS was used to drive the reporter GUS gene, the GUS activity was detected only in mature pollen. Interestingly, the LOC_Os10g34360 URS was found to be vascular bundle preferred and its activities were restricted only to vascular bundles of leaves, roots and florets. In addition, we have also identified two URSs from genes LOC_Os02G15090 and LOC_Os06g31070 expressed in a seed-preferred manner showing the highest expression levels of GUS activities in mature seeds. CONCLUSION: By genome-wide analysis, we have identified tissue-preferred URSs, five of which were further characterized using transgenic plants harboring URS::GUS constructs. These data might provide some evidence for possible functions of the genes and be a valuable resource for tissue-preferred candidate URSs for plant transgenesis.

An X chromosome-wide association analysis identifies variants in GPR174 as a risk factor for Graves' disease.

BACKGROUND: Graves' disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). METHODS: We re-examined the X chromosome data from our recent GWAS for Graves' disease by including males that were previously excluded from the X chromosome analyses. The data were analysed using logistic regression analysis including sex as a covariate, and an additive method assuming X chromosome inactivation, implemented in snpMatrix. RESULTS: A cluster of single nucleotide polymorphism (SNPs) at Xq21.1 was found showing association with genome-wide significance, among which rs3827440 was a non-synonymous SNP of GPR174 (P(logistic regression)= 9.52×10(-8); P(snpMatrix)=4.60×10(-9); OR=1.76, 95% CI 1.45 to 2.13). The association was reproduced in an independent sample collection set including 4564 Graves' disease cases and 3968 sex matched controls (combined P(logistic regression)=5.53×10(-21); combined P(snpMatrix)=4.26×10(-22); OR=1.69, 95% CI 1.53 to 1.86). Notably, GPR174 was widely expressed in immune related tissues and rs3827440 genotypes were associated with distinct mRNA levels (p=0.002). GPR174 did not show sex biased gene expression in our expression analysis. Resequencing study suggested the contribution of some rare variants in the GPR174 gene region to disease risk with a collapsing p value of 1.16×10(-3). CONCLUSIONS: The finding of an X-linked risk locus for Graves' disease expands our understanding of the role of the X chromosome in disease susceptibility.

LHP1 and INO80 cooperate with ethylene signaling for warm ambient temperature response by activating specific bivalent genes.

Ethylene signaling has been indicated as a potential positive regulator of plant warm ambient temperature response but its underlying molecular mechanisms are largely unknown. Here, we show that LHP1 and INO80 cooperate with ethylene signaling for warm ambient temperature response by activating specific bivalent genes. We found that the presence of warm ambient temperature activates ethylene signaling through EIN2 and EIN3, leading to an interaction between LHP1 and accumulated EIN2-C to co-regulate a subset of LHP1-bound genes marked by H3K27me3 and H3K4me3 bivalency. Furthermore, we demonstrate that INO80 is recruited to bivalent genes by interacting with EIN2-C and EIN3, promoting H3K4me3 enrichment and facilitating transcriptional activation in response to warm ambient temperature. Together, our findings illustrate a novel mechanism wherein ethylene signaling orchestrates LHP1 and INO80 to regulate warm ambient temperature response through activating specific bivalent genes in Arabidopsis.

Active role of iron-dependent AOM in paddy fields under different long-term fertilizer management schemes.

Iron-dependent anaerobic oxidation of methane (iron-AOM) has recently been reported to occur in paddy soils, but its actual role and regulation remain unclear. Here, we confirmed the occurrence of iron-AOM at different layers of paddy soils (0-10 cm, 10-20 cm, and 30-40 cm) across tillering, elongation, flowering, and ripening periods under three long-term fertilizer management schemes (CK-unamended, CF-chemical fertilizer, and CFS-chemical fertilizer with straw). The iron-AOM activity contributed 41 % to total AOM, which was greater than that of nitrite- (32 %) and nitrate-AOM (27 %). The iron-AOM activity varied significantly with soil layers, growth periods and fertilizer types, with layer being the most important variable. Soil moisture content and organic carbon content were most significant influencing factors on the AOM activity, and a Candidatus Methanoperedens ferrireducens-like lineage potentially catalyzed iron-AOM. Our results suggest that iron-AOM has an important potential for mitigating methane emissions from rice paddies.

Exploring the mechanism of Icariin in the treatment of depression through BDNF-TrkB pathway based on network pharmacology.

Depression has increasingly become a disease that seriously harms people's mental health around the world. Icariin is the main active component of Epimedii Herba and effective on protecting the central nervous system. The purpose of this study was to explore the mechanism of icariin against depression based on network pharmacology and molecular docking. The potential targets related to icariin and depression were obtained by accessing network databases. The Metascape database was used for the enrichment analysis of GO function and KEGG pathways. A common target-pathway network was constructed using Cytoscape 3.9.0 software. Schrödinger Maestro 12.8 was adopted to evaluate the binding ability of icariin to core targets. Mice were induced by the chronic unpredictable mild stress (CUMS) model, and the prediction results of this study were verified by in vivo experiments. A total of 109 and 3294 targets were identified in icariin and depression, respectively. The common target-pathway network was constructed, and 7 core target genes were obtained. The molecular docking results of the 7 core target genes with icariin showed good affinity. In a CUMS-induced depression model, we found that icariin could effectively improve depression-like behavior of mice, increase the expression of monoamine neurotransmitters 5-hydroxytryptamine, dopamine, and norepinephrine, decrease the secretion of inflammatory factors tumor necrosis factor-α, interleukin-6, and interleukin-1ß, and upregulate the relative expression levels of BDNF, p-TrkB/TrkB, p-Akt/Akt, p-CREB/CREB, MAPK3, MAPK1, Bcl-2, EGFR, and mTOR. The results suggest that icariin has certain antidepressant effects, and may be mediated by the BDNF-TrkB signaling pathway. It provides new ideas for the treatment of depression in the future.

A Review of Brain-Inspired Cognition and Navigation Technology for Mobile Robots.

Brain-inspired navigation technologies combine environmental perception, spatial cognition, and target navigation to create a comprehensive navigation research system. Researchers have used various sensors to gather environmental data and enhance environmental perception using multimodal information fusion. In spatial cognition, a neural network model is used to simulate the navigation mechanism of the animal brain and to construct an environmental cognition map. However, existing models face challenges in achieving high navigation success rate and efficiency. In addition, the limited incorporation of navigation mechanisms borrowed from animal brains necessitates further exploration. On the basis of the brain-inspired navigation process, this paper launched a systematic study on brain-inspired environment perception, brain-inspired spatial cognition, and goal-based navigation in brain-inspired navigation, which provides a new classification of brain-inspired cognition and navigation techniques and a theoretical basis for subsequent experimental studies. In the future, brain-inspired navigation technology should learn from more perfect brain-inspired mechanisms to improve its generalization ability and be simultaneously applied to large-scale distributed intelligent body cluster navigation. The multidisciplinary nature of brain-inspired navigation technology presents challenges, and multidisciplinary scholars must cooperate to promote the development of this technology.

Simultaneous methane mitigation and nitrogen removal by denitrifying anaerobic methane oxidation in lake sediments.

Methane (CH4) is a potent greenhouse gas, with lake ecosystems significantly contributing to its global emissions. Denitrifying anaerobic methane oxidation (DAMO) process, mediated by NC10 bacteria and ANME-2d archaea, links global carbon and nitrogen cycles. However, their potential roles in mitigating methane emissions and removing nitrogen from lake ecosystems remain unclear. This study explored the spatial variations in activities of nitrite- and nitrate-DAMO and their functional microbes in Changdanghu Lake sediments (Jiangsu Province, China). The results showed that although the average abundance of ANME-2d archaea (5.0 × 106 copies g-1) was significantly higher than that of NC10 bacteria (2.1 × 106 copies g-1), the average potential rates of nitrite-DAMO (4.59 nmol 13CO2 g-1 d-1) and nitrate-DAMO (5.01 nmol 13CO2 g-1 d-1) showed no significant difference across all sampling sites. It is estimated that nitrite- and nitrate-DAMO consumed approximately 6.46 and 7.05 mg CH4 m-2 d-1, respectively, which accordingly achieved 15.07-24.95 mg m-2 d-1 nitrogen removal from the studied lake sediments. Statistical analyses found that nitrite- and nitrate-DAMO activities were both significantly related to sediment nitrate contents and ANME-2d archaeal abundance. In addition, NC10 bacterial and ANME-2d archaeal community compositions showed significant correlations with sediment organic carbon content and water depth. Overall, this study underscores the dual roles of nitrite- and nitrate-DAMO processes in CH4 mitigation and nitrogen elimination and their key environmental impact factors (sediment organic carbon and inorganic nitrogen contents, and water depth) in shallow lake, enhancing the understanding of carbon and nitrogen cycles in freshwater aquatic ecosystems.

Equal importance of humic acids and nitrate in driving anaerobic oxidation of methane in paddy soils.

Methane (CH4) is both generated and consumed in paddy soils, where anaerobic oxidation of methane (AOM) serves as a crucial process for mitigating CH4 emissions. Although the participation of humic acids (HA) and nitrate in AOM has been recognized, their relative roles and significance in paddy soils remain insufficiently investigated. In this study, we explored the potential activity of AOM driven by HA and nitrate, as well as the composition of archaeal communities in paddy soils across different rice growth periods and fertilization treatments. AOM activity ranged from 0.81 to 1.33 and 1.26 to 2.38 nmol of 13CO2 g-1 (dry soil) day-1 with HA and nitrate, respectively. No significant differences (p < 0.05) were observed between the AOM activity driven by HA and nitrate across the three fertilization treatments. According to AOM activity, the annual consumption of CH4 was estimated at approximately 0.49 ± 0.06 and 0.83 ± 0.19 Tg for AOM processes driven by HA and nitrate in Chinese paddy soils. Nitrate-driven AOM activity exhibited a positive (p < 0.05) correlation with the abundance of the ANME-2d mcrA gene but a negative (p < 0.05) correlation with the content of dissolved organic carbon. Intriguingly, HA-driven AOM activity was only correlated positively with the nitrate-driven AOM activity. Soil water content, soil organic carbon, nitrate and nitrite contents were significantly correlated with the relative abundance of methanogenic and methanotrophic archaea. These results identified the potential importance of HA and nitrate in driving AOM processes within paddy soils, providing a comprehensive understanding of the complex microbial processes regulating greenhouse gas emissions from paddy soils.

Non-invasive detection of tumor markers in salivary extracellular vesicles based on digital PCR chips.

The World Health Organization (WHO) has stated that countless cancer patients could be saved if early detection and treatment were available. However, current clinical evaluation of tumors still relies primarily on imaging examinations and tissue biopsies. These methods not only require sophisticated equipment, but also have high false positive rates or invasive problems. Here, we describe a digital polymerase chain reaction (dPCR) chip for the detection of biomarkers in salivary extracellular vesicles (SEVs), which can be used to identify markers for the early diagnosis of tumors. Based on microfluidic technology fine microstructure and microfluidics operations, this dPCR chip can accurate quantitative SEVs in a variety of tumor markers, and shows extremely strong sensitivity (10 copies). In the detection of clinical samples, the chip can effectively distinguish lung cancer cases from normal controls (P < 0.001; two-tailed t-test), and in the detection of extremely low concentration samples, it shows considerably higher precise quantitative ability than quantitative real-time polymerase chain reaction (qPCR). Overall, this study may shed new light on non-invasive early screening of tumor markers by detecting extracellular vesicle-associated markers in saliva.

Glial Cells of the Central Nervous System: A Potential Target in Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of the male urological system while the etiology and treatment of CP/CPPS remain a thorny issue. Cumulative research suggested a potentially important role of glial cells in CP/CPPS. This narrative review retrospected literature and grasped the research process about glial cells and CP/CPPS. Three types of glial cells showed a crucial connection with general pain and psychosocial symptoms. Microglia might also be involved in lower urinary tract symptoms. Only microglia and astrocytes have been studied in the animal model of CP/CPPS. Activated microglia and reactive astrocytes were found to be involved in both pain and psychosocial symptoms of CP/CPPS. The possible mechanism might be to mediate the production of some inflammatory mediators and their interaction with neurons. Glial cells provide a new insight to understand the cause of complex symptoms of CP/CPPS and might become a novel target to develop new treatment options. However, the activation and action mechanism of glial cells in CP/CPPS needs to be further explored.

Comparison of pharmacokinetics, biodistribution, and excretion of free and bound Nε-carboxymethyllysine in rats by HPLC-MS/MS.

As a representative product of advanced glycation end products, Nɛ-carboxymethyllysine (CML) exists in free and bound forms in vivo and in food with different bioavailability. To thoroughly understand the bioavailability of free Nɛ-carboxymethyllysine (CML) and bovine serum albumin (BSA)-CML in vivo after intragastric administration, pharmacokinetics, biodistribution, and excretion of CML in rats were investigated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetics results revealed that free CML peaked at 1.83 h (1684.72 ± 78.08 ng/mL) and 1.33 h (1440.84 ± 72.48 ng/mL) in serum after intragastric administration of free CML and BSA-CML, demonstrating the higher absorption of free CML than BSA-CML. Besides, dietary free CML exhibited a relatively lower body clearance and tissue distribution than dietary BSA-CML based on the apparent volume of distribution and body clearance. Moreover, free CML was concentrated in the kidneys, indicating that kidneys were the target organ for the uptake of absorbed free CML. Additionally, the total excretion rate of CML in urine and feces were 37% and 60% after oral administration of free CML and BSA-CML. These results shed pivotal light on a better understanding of the biological effects of free and bound CML on health.