CoNi-N/P-Doped Carbon Nanotubes as Catalysts for Efficient Oxygen Reduction Reaction.

Transition metals (TMs) supported by heteroatom-doped carbon materials are considered to be the potential alternatives to the Pt/C catalyst owing to their low cost, outstanding electrocatalytic efficiency, and excellent electrochemical durability. In this paper, N/P-doped carbon nanotube (CNT) (N/P-CNT)-supported monometallic (Co, Ni) and bimetallic (CoNi) catalysts were synthesized by one-step pyrolysis using diammonium hydrogen phosphate, 2-methylimidazole and organometallic salts as precursors, and the CNT as the catalyst carrier; the effects of transition TM types and pyrolysis temperature (Tp) on the microstructure and electrochemical properties were explored. The analysis exhibited that the CoNi bimetallic catalyst was superior to both Co and Ni monometallic catalysts, and the catalysts pyrolyzed at 900 °C exhibited a better graphitization degree. The optimal CoNi-N/P-CNT-900 displayed remarkable oxygen reduction reaction electrocatalytic performance with a half-wave potential (E1/2) of 0.86 V and excellent methanol tolerance and stability. Moreover, the Zn-air battery coated with CoNi-N/P-CNT-900 demonstrated a larger open circuit voltage of 1.577 V, a larger peak power density of 212.89 mW cm-2 at 357.8 mA cm-2, as well as a higher specific capacity of 799 mA h gZn-1, superior to that of the Pt/C catalyst (1.492 V, 96.04 mW cm-2 at 216.8 mA cm-2, 735 mA h gZn-1), showing outstanding practical value. This study is expected to promote the commercialization of the electrocatalysts.

Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet.

The Cecum is a key site for cellulose digestion in nutrient metabolism of intestine, but its mechanisms of microbial and gene interactions has not been fully elucidated during pathogenesis of obesity. Therefore, the cecum tissues of the New Zealand rabbits and their contents between the high-fat diet-induced group (Ob) and control group (Co) were collected and analyzed using multi-omics. The metagenomic analysis indicated that the relative abundances of Corallococcus_sp._CAG:1435 and Flavobacteriales bacterium species were significantly lower, while those of Akkermansia glycaniphila, Clostridium_sp._CAG:793, Mycoplasma_sp._CAG:776, Mycoplasma_sp._CAG:472, Clostridium_sp._CAG:609, Akkermansia_sp._KLE1605, Clostridium_sp._CAG:508, and Firmicutes_bacterium_CAG:460 species were significantly higher in the Ob as compared to those in Co. Transcriptomic sequencing results showed that the differentially upregulated genes were mainly enriched in pathways, including calcium signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway, while the differentially downregulated genes were mainly enriched in pathways of NF-kappaB signaling pathway and T cell receptor signaling pathway. The comparative analysis of metabolites showed that the glycine, serine, and threonine metabolism and cysteine and methionine metabolism were the important metabolic pathways between the two groups. The combined analysis showed that CAMK1, IGFBP6, and IGFBP4 genes were highly correlated with Clostridium_sp._CAG:793, and Akkermansia_glycaniphila species. Thus, the preliminary study elucidated the microbial and gene interactions in cecum of obese rabbit and provided a basis for further studies in intestinal intervention for human obesity.

Photoinduced Redox Cascade Reaction of Isatins and Aliphatic Carboxylic Acids to Access 6-Hydroxyindoloquinazolinones.

A visible-light-induced cascade reaction is described for the one-pot synthesis of 6-hydroxyindoloquinazolinones using isatins (or isatins and isatoic anhydrides) and aliphatic carboxylic acids. The method provides 36 desired products in 33-96% yield, exhibiting broad substrate scope and good functional group tolerance. This approach utilizes inexpensive and commercially available starting materials, enabling the direct construction of high-value complex structures under mild conditions without the need for photocatalyst, showcasing significant applicability and environmental friendliness.

Synchronous influence of soil amendments on alkylmercury and methane emissions in mercury-contaminated paddy soil.

Mercury (Hg) alkylation and methane (CH4) emissions pose significant global concerns. Paddy soil, due to its long-term anaerobic conditions and abundant organic matter, is hotspots for soil Hg alkylation and CH4 emissions. However, the relevance between Hg alkylation and CH4 emissions, especially their simultaneous reduction strategies, remains poorly understood. Here, we investigated the effects of biochar (BC), selenium (Se) and rice straw (RS) amendments on Hg alkylation and CH4 emissions in paddy soil, and the accumulation of Hg speciation. Results found that both BC and RS amendments significantly increased the levels of soil organic carbon (SOC) and humification index (HIX). Furthermore, BC decreased the concentrations of Hg(II), methylmercury (MeHg) and ethylmercury (EtHg) by 63.1%, 53.6% and 100% in rice grains. However, RS increased Hg(II) concentration but decreased the total Hg (THg), MeHg and EtHg concentrations in rice grains. Compared to the CK, RS significantly increased CH4 emissions, while BC decreased CH4 emissions, and Se showed no significant difference. Se amendment increased the Hg(II) and EtHg concentrations by 20.3% and 17.0% respectively, and decreased the MeHg concentration in grains by 58.3%. Both BC and RS impacted the abundance of methanogens by enhancing SOC and HIX, subsequently modulating the relevance between Hg alkylation and CH4 emissions. These findings provide insights into the relevance between Hg alkylation and CH4 emissions and propose potential mitigation mechanisms in Hg-contaminated paddy soil.

Association between oral microbial nitrate metabolism and poor prognosis in acute ischemic stroke patients with a history of hypertension.

Background: Oral microbes mediate the production of nitric oxide (NO) through the denitrification pathway. This study aimed to investigate the association between oral microbial nitrate metabolism and prognosis in acute ischemic stroke (AIS) patients. Methods: This prospective, observational, single-center cohort study included 124 AIS patients admitted within 24 hours of symptom onset, with 24-hour ambulatory blood pressure data. Oral swabs were collected within 24 hours. Hypertensive AIS patients were stratified by the coefficient of variation (CV) of 24-hour systolic blood pressure. Microbial composition was analyzed using LEfSe and PICRUSt2 for bacterial and functional pathway identification. Results: Significant differences in oral microbiota composition were observed between hypertensive AIS patients with varying CVs. Lower CV groups showed enrichment of nitrate-reducing bacteria and "Denitrification, nitrate => nitrogen" pathways. The TAX score of oral nitrate-reducing bacteria, derived from LASSO modeling, independently correlated with 90-day modified Rankin Scale scores, serving as an independent risk factor for poor prognosis. Mediation analyses suggested indirect that the TAX score not only directly influences outcomes but also indirectly affects them by modulating 24-hour systolic blood pressure CV. Conclusions: AIS patients with comorbid hypertension and higher systolic blood pressure CV exhibited reduced oral nitrate-reducing bacteria, potentially worsening outcomes.

Structure and scaling of Kitaev chain across a quantum critical point in real space.

The spatial Kibble-Zurek mechanism is applied to the Kitaev chain with inhomogeneous pairing interactions that vanish in half of the lattice and result in a quantum critical point separating the superfluid and normal-gas phases in real space. The weakly-interacting BCS theory predicts scaling behavior of the penetration of the pair wavefunction into the normal-gas region different from conventional power-law results due to the non-analytic dependence of the BCS order parameter on the interaction. The Bogoliubov-de Gennes (BdG) equation produces numerical results confirming the scaling behavior and hints complications in the strong-interaction regime. The limiting case of the step-function quench reveals the dominance of the BCS coherence length in absence of additional length scale. Furthermore, the energy spectrum and wavefunctions from the BdG equation show abundant in-gap states from the normal-gas region in addition to the topological edge states.

Interleukin 25 promotes muscle regeneration in sarcopenia by regulating macrophage-mediated Sonic Hedgehog signaling.

OBJECTIVE: Sarcopenia manifests as a chronic, low-level inflammation along with multiple inflammatory cells infiltration. Interleukin (IL)-25 can regulate the function of macrophages. However, the specific role and mechanisms through which IL-25 functions in sarcopenia are still not fully understood and require further investigation. METHODS: Aged mice were utilized as sarcopenia models and examined the expression of inflammatory factors. To investigate the effects of IL-25 on sarcopenia, the model mice received IL-25 treatment and underwent in vivo adoptive transfer of IL-25-induced macrophages. Meanwhile, RAW264.7 cells, bone marrow-derived macrophages, satellite cells and C2C12 cells were used in vitro. Shh insufficiency was induced through intramuscular administration of SHH-shRNA adenoviruses. Then, various assays including scratch wound, cell counting kit-8 and Transwell assays, as well as histological staining and molecular biological methods, were conducted. RESULTS: Aged mice exhibited an accelerated decline in muscle strength and mass, along with an increased muscle lipid droplets and macrophage infiltration, and decreased IL-25 levels compared to the young group. IL-25 therapy and the transfer of IL-25-preconditioned macrophages could improve these conditions by promoting M2 macrophage polarization in vivo as well as in vitro. M2 macrophage conditioned medium enhanced satellite cell proliferation and migration, as well as the vitality, migration, and differentiation of C2C12 cells in vitro. Furthermore, IL-25 enhanced Shh expression in macrophages in vitro, and activated the Shh signaling pathway in muscle tissue of aged mice, which could be suppressed by either the inhibitor cyclopamine or Shh knockdown. Mechanistic studies showed that Shh insufficiency suppressed the activation of Akt/mTOR signaling pathway in muscle tissue of aged mice. CONCLUSION: IL-25 promotes the secretion of Shh by M2 macrophages and activates the Shh/Akt/mTOR signaling pathway, which improves symptoms and function in sarcopenia mice. This suggests that IL-25 has potential as a therapeutic agent for treating sarcopenia.

Photoredox-Neutral Radical-Radical Cross-Coupling of Isatins and Benzyl Carboxylic Acids.

A photoredox-neutral radical-radical cross-coupling is described for the synthesis of 3-hydroxy-3-alkyloxindoles using isatins and benzyl carboxylic acids as substrates and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) as the photocatalyst. The method features a broad substrate scope and good functional group tolerance, providing 30 sterically hindered alcohols with moderate to excellent yields. This approach utilizes inexpensive and commercially available starting materials, avoiding the use of transition metals, extra oxidants/reductants, and harsh reaction conditions, showcasing significant applicability and environmental friendliness.

NMN Synbiotics: A Multifaceted Therapeutic Approach for Alzheimer's Disease.

With the aging global population, Alzheimer's disease (AD) has become a significant social and economic burden, necessitating the development of novel therapeutic strategies. This study investigates the therapeutic potential of nicotinamide mononucleotide (NMN) synbiotics, a combination of NMN, Lactiplantibacillus plantarum CGMCC 1.16089, and lactulose, in mitigating AD pathology. APP/PS1 mice were supplemented with NMN synbiotics and compared against control groups. The effects on amyloid-ß (Aß) deposition, intestinal histopathology, tight junction proteins, inflammatory cytokines, and reactive oxygen species (ROS) levels were assessed. NMN synbiotics intervention significantly reduced Aß deposition in the cerebral cortex and hippocampus by 67% and 60%, respectively. It also ameliorated histopathological changes in the colon, reducing crypt depth and restoring goblet cell numbers. The expression of tight junction proteins Claudin-1 and ZO-1 was significantly upregulated, enhancing intestinal barrier integrity. Furthermore, NMN synbiotics decreased the expression of proinflammatory cytokines IL-1ß, IL-6, and TNF-α, and reduced ROS levels, indicative of attenuated oxidative stress. The reduction in Aß deposition, enhancement of intestinal barrier function, decrease in neuroinflammation, and alleviation of oxidative stress suggest that NMN synbiotics present a promising therapeutic intervention for AD by modulating multiple pathological pathways. Further research is required to elucidate the precise mechanisms, particularly the role of the NLRP3 inflammasome pathway, which may offer a novel target for AD treatment.

Performance and mechanism of sulfadiazine and norfloxacin adsorption from aqueous solution by magnetic coconut shell biochar.

In this study, magnetic coconut shell biochar loaded with spherical Fe3O4 and γ-Fe2O3 particles was successfully synthesized using a chemical coprecipitation method. The magnetic biochar exhibited a good magnetic separability and environmental security. The maximum sulfadiazine (SDZ) and norfloxacin (NOR) removal efficiencies were 94.8% and 92.3% at pH 4 and 25 °C with adsorbent dosage of 2.5 g/L, respectively. When antibiotic concentrations ranged from 5 to 50 mg/L, the theoretical maximum adsorption capacities of SDZ and NOR were 16.7 mg/g and 25.8 mg/g, respectively. The Langmuir isotherm and pseudo-second-order kinetic models could better describe the adsorption process of both antibiotics, implying the monolayer chemical adsorption. The thermodynamic analysis indicated that the adsorption process was spontaneous and endothermic. The ionic strength had no significant effect on the adsorption behavior of either antibiotic. Combined with BET, FTIR, and XPS results, the dominant mechanisms for SDZ and NOR adsorption were pore filling, π-π electron-donor-acceptor interaction, hydrogen bonds and surface complexation. Moreover, Lewis acid-base interaction also contributed to SDZ adsorption.

The impact of artificial liver support system on intestinal microbiota and serum bile acid profiles in patients with acute-on-chronic liver failure: a prospective cohort study.

BACKGROUND: Acute-on-chronic liver failure (ACLF) patients exhibit an imbalance in intestinal microbiota, and bile acids (BAs) can affect the composition of intestinal microbiota. Although Artificial liver support system (ALSS) is a treatment for ACLF, the impact of ALSS on intestinal microbiota and serum BA profiles of ACLF patients remains unclear. METHODS: A prospective study was conducted, which included 51 patients diagnosed with ACLF. These patients were stratified into two groups based on the utilization of an ALSS during their treatment period: a standard medical treatment group (SMT group), comprising 19 patients, and an ALSS combined with SMT group (ALSS group), comprising 32 patients. Blood and stool samples were collected from the patients on the day of admission and 14 days after treatment. Additionally, eight healthy controls were recruited, and their stool samples were also collected. The intestinal microbiota was sequenced using the 16S rRNA sequencing technique, while the serum BA profiles were determined using ultra-performance liquid chromatography/mass spectrometry. RESULTS: ACLF patients exhibited imbalances in intestinal microbiota and abnormalities in BA profiles. Compared to SMT alone, the combined ALSS and SMT was more effective in regulating intestinal microbiota imbalance and increasing the concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid. Correlation analysis revealed a significant correlation between intestinal microbiota and Bas. Furthermore, the preliminary correlation heatmap indicated that the Faecalibaculum, Gemmiger, and taurochenodeoxycholic acid were associated with clinical improvement. CONCLUSIONS: Our study identified the compositional characteristics of the intestinal microbiota and serum BA in ACLF patients, emphasizing the impact of ALSS on both intestinal microbiota and serum BA profiles.

Development and validation of a machine learning-based model to predict isolated post-challenge hyperglycemia in middle-aged and elder adults: Analysis from a multicentric study.

INTRODUCTION: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. METHODS: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. RESULTS: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811-0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786-0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635-0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/. CONCLUSIONS: The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population.

Application of machine reading comprehension techniques for named entity recognition in materials science.

Materials science is an interdisciplinary field that studies the properties, structures, and behaviors of different materials. A large amount of scientific literature contains rich knowledge in the field of materials science, but manually analyzing these papers to find material-related data is a daunting task. In information processing, named entity recognition (NER) plays a crucial role as it can automatically extract entities in the field of materials science, which have significant value in tasks such as building knowledge graphs. The typically used sequence labeling methods for traditional named entity recognition in material science (MatNER) tasks often fail to fully utilize the semantic information in the dataset and cannot effectively extract nested entities. Herein, we proposed to convert the sequence labeling task into a machine reading comprehension (MRC) task. MRC method effectively can solve the challenge of extracting multiple overlapping entities by transforming it into the form of answering multiple independent questions. Moreover, the MRC framework allows for a more comprehensive understanding of the contextual information and semantic relationships within materials science literature, by integrating prior knowledge from queries. State-of-the-art (SOTA) performance was achieved on the Matscholar, BC4CHEMD, NLMChem, SOFC, and SOFC-Slot datasets, with F1-scores of 89.64%, 94.30%, 85.89%, 85.95%, and 71.73%, respectively in MRC approach. By effectively utilizing semantic information and extracting nested entities, this approach holds great significance for knowledge extraction and data analysis in the field of materials science, and thus accelerating the development of material science.Scientific contributionWe have developed an innovative NER method that enhances the efficiency and accuracy of automatic entity extraction in the field of materials science by transforming the sequence labeling task into a MRC task, this approach provides robust support for constructing knowledge graphs and other data analysis tasks.

Knowledge, attitude, and practice toward interstitial lung disease among patients: a cross-sectional study.

Objective: To explore the knowledge, attitude, and practice (KAP) toward interstitial lung disease (ILD) among patients and analyze the factors affecting KAP. Methods: This cross-sectional study enrolled patients with ILD treated at the Respiratory Department of Shanghai Pulmonary Hospital between January 2023 and June 2023. A self-administered questionnaire was developed to evaluate their KAP toward ILD through convenient sampling. Multivariate regression analysis and structural equation model (SEM) were used to analyze the factors influencing KAP and their interactions. Results: A total of 397 patients were enrolled, with 61.71% male. The mean KAP scores were 4.60 ± 3.10 (possible range: 0-12), 16.97 ± 2.16 (possible range: 5-25), and 32.60 ± 7.16 (possible range: 9-45), respectively. Multivariate logistic regression analysis showed that junior high school [OR = 2.003, 95%CI: 1.056-3.798, p = 0.033], high school and above [OR = 2.629, 95%CI: 1.315-5.258, p = 0.006], and duration of disease ≥5 years [OR = 1.857, 95%CI: 1.132-3.046, p = 0.014] were independently associated with adequate knowledge. The knowledge [OR = 1.108, 95%CI: 1.032-1.189, p = 0.005] and duration of disease ≥5 years [OR = 0.525, 95%CI: 0.317-0.869, p = 0.012] were independently associated with a positive attitude. The knowledge [OR = 1.116, 95%CI: 1.036-1.202, p = 0.004], attitude [OR = 1.180, 95%CI: 1.061-1.312, p = 0.002], and the age of >70 years [OR = 0.447, 95%CI: 0.245-0.817, p = 0.009] were independently associated with the proactive practice. SEM showed that patients' knowledge of ILD directly affected their attitude (ß = 0.842, p < 0.001) and practice (ß = 0.363, p < 0.001), and their attitude also affected their practice (ß = 0.347, p = 0.014). Conclusion: Patients with ILD in China had poor knowledge, intermediate attitude, and proactive practice toward ILD, which suggests that the health education of patients should be further strengthened.

Mixing and Thermal Transport Behavior in a Pin or Non-Pin Extruder Equipped with a Field Synergy Elongation Screw.

The ductile forming process of a polymer in a standard screw extruder and pin-barrel extruder, equipped with or without a field synergy elongation screw, was investigated by the finite element method. In order to assess the mixing and heat transfer capabilities of screws, characteristic parameters such as the mixing efficiency, segregation scale, and temperature distribution of different structures were analyzed and compared. The results indicated that the flow pattern of the polymer melt in the extruder was significantly influenced by the screw structure and was improved by the newly designed field synergy screw configuration, which brought a desirable elongational flow to enhance the radial convection. This was attributed to the unique radial wedge-shaped repeated convergence region of the field synergy elongation screw, increasing the synergistic effect between the velocity field, velocity gradient field, and temperature gradient field and thus improving the heat transfer and mixing efficiency. After adding barrel pins, the flow was forced to split, resulting in a more significant stretching effect on the melt. The field synergy effect in the pin mixed region was strengthened, which further increased the heat and mass transfer efficiency of the screw. However, increasing barrel pins could also lead to undesired temperature fluctuation and flow resistance, which have a negative impact on the melt uniformity. This study offers an important reference for optimizing screw structure to obtain strong mixing and heat transfer performances.

Protocol to use protein language models predicting and following experimental validation of function-enhancing variants of thymine-N-glycosylase.

Protein language models (PLMs) are machine learning tools trained to predict masked amino acids within protein sequences, offering opportunities to enhance protein function without prior knowledge of their specific roles. Here, we present a protocol for optimizing thymine-DNA-glycosylase (TDG) using PLMs. We describe steps for "zero-shot" enzyme optimization, construction of plasmids, double plasmid transfection, and high-throughput sequencing and data analysis. This protocol holds promise for streamlining the engineering of gene editing tools, delivering improved activity while minimizing the experimental workload. For complete details on the use and execution of this protocol, please refer to He et al.1.

Clinical Outcome Assessment of Colistin Sulfate in Children with Carbapenem-Resistant Organism Infections: First Data from China.

OBJECT: Colistin sulfate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese pediatric patients with carbapenem-resistant organism (CRO) infections. The purpose of this short communication is to provide a brief overview of the findings to date. METHODS: We reviewed the electronic medical records of pediatric patients (aged 9-17 years) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions. RESULTS: A total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment. CONCLUSION: In this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of CRO infections in Chinese children.

From cubane-assembled Mn-oxo clusters to monodispersed manganese oxide colloidal nanocrystals.

The assemblies of [M4O4] (M = metal) cubanes represent a fascinating class of materials for a variety of application fields. Although such a structural characteristic is relatively common in small molecules and in extended bulk solids, high nuclearity clusters composed of multiple [M4O4] units as their backbones are rare. In this work, we report two new Mn-oxo clusters, MnII 8MnIII 10O10(OOCMe)12(OMe)14(py)2 ([Mn18-Ac]) and MnII 4MnIII 14O14(OOCCMe3)8(OMe)14(MeOH)5(py) ([Mn18-Piv]), whose core structures are assemblies of either 6- or 7-cubanes in different packing patterns, which have been unambiguously revealed by single crystal X-ray diffraction technique. The cubane-assembled structural features can be deemed as the embryonic structures of the bulk manganese oxide. Herein, this report demonstrates the first case study of utilizing Mn-oxo clusters as precursors for the preparation of manganese oxide nanocrystals, which has never been explored before. Through a simple colloidal synthetic approach, high-quality, monodisperse Mn3O4 nanocrystals can be readily prepared by employing both precursors, while their morphologies were found to be quite different. This work confirms that the structural similarity between precursors and nanomaterials is instrumental in affording more kinetically efficient pathways for materials formation, and the structure of the precursor has a significant impact on the morphology of final nanocrystal products.

RNA Adduction Resulting from the Metabolic Activation of Myristicin by P450 Enzymes and Sulfotransferases.

Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by SN1 and/or SN2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.

Exploring the potential of the TCR repertoire as a tumor biomarker (Review).

T cells play an important role in adaptive immunity. Mature T cells specifically recognize antigens on major histocompatibility complex molecules through T-cell receptors (TCRs). As the TCR repertoire is highly diverse, its analysis is vital in the assessment of T cells. Advances in sequencing technology have provided convenient methods for further investigation of the TCR repertoire. In the present review, the TCR structure and the mechanisms by which TCRs function in tumor recognition are described. In addition, the potential value of the TCR repertoire in tumor diagnosis is reviewed. Furthermore, the role of the TCR repertoire in tumor immunotherapy is introduced, and the relationships between the TCR repertoire and the effects of different tumor immunotherapies are discussed. Based on the reviewed literature, it may be concluded that the TCR repertoire has the potential to serve as a biomarker for tumor prognosis. However, a wider range of cancer types and more diverse subjects require evaluation in future research to establish the TCR repertoire as a biomarker of tumor immunity.