Indoxacarb triggers autophagy and apoptosis through ROS accumulation mediated by oxidative phosphorylation in the midgut of Bombyx mori.

Indoxacarb has been widely utilized in agricultural pest management, posing a significant ecological threat to Bombyx mori, a non-target economic insect. In the present study, short-term exposure to low concentration of indoxacarb significantly suppressed the oxidative phosphorylation pathway, and resulted in an accumulation of reactive oxygen species (ROS) in the midgut of B. mori. While, the ATP content exhibited a declining trend but there was no significant change. Moreover, indoxacarb also significantly altered the transcription levels of six autophagy-related genes, and the transcription levels of ATG2, ATG8 and ATG9 were significantly up-regulated by 2.56-, 1.90-, and 3.36-fold, respectively. The protein levels of ATG8-I and ATG8-II and MDC-stained frozen sections further suggested an increase in autophagy. Furthermore, the protein level and enzyme activity of CASP4 showed a significant increase in accordance with the transcription levels of apoptosis-related genes, indicating the activation of the apoptotic signaling pathway. Meanwhile, the induction of apoptosis signals in the midgut cells triggered by indoxacarb was confirmed through TUNEL staining. These findings suggest that indoxacarb can promote the accumulation of ROS by inhibiting the oxidative phosphorylation pathway, thereby inducing autophagy and apoptosis in the midgut cells of B. mori.

Electrochemical Knocking-Down of Zn Metal Clusters into Single Atoms.

Single Atoms Catalysts (SACs) have emerged as a class of highly promising heterogeneous catalysts, where the traditional bottom-up synthesis approaches often encounter considerable challenges in relation to aggregation issues and poor stability. Consequently, achieving densely dispersed atomic species in a reliable and efficient manner remains a key focus in the field. Herein, we report a new facile electrochemical knock-down strategy for the formation of SACs, whereby the metal Zn clusters are transformed into single atoms. While a defect-rich substrate plays a pivotal role in capturing and stabilizing isolated Zn atoms, the feasibility of this novel strategy is demonstrated through a comprehensive investigation, combining experimental and theoretical studies. Furthermore, when studied in exploring for potential applications, the material prepared shows a remarkable improvement of 58.21% for the Li+ storage and delivers a capacity over 300 Wh kg-1 after 500 cycles upon the transformation of Zn clusters into single atoms.

A Hybrid Redox-Mediated Zinc-Air Fuel Cell for Scalable and Sustained Power Generation.

Zinc-air batteries (ZABs) have attracted considerable attention for their high energy density, safety, low noise, and eco-friendliness. However, the capacity of mechanically rechargeable ZABs was limited by the cumbersome procedure for replacing the zinc anode, while electrically rechargeable ZABs suffer from issues including low depth of discharge, zinc dendrite and dead zinc formation, and sluggish oxygen evolution reaction, etc. To address these issues, we report a hybrid redox-mediated zinc-air fuel cell (HRM-ZAFC) utilizing 7,8-dihydroxyphenazine-2-sulfonic acid (DHPS) as the anolyte redox mediator, which shifts the zinc oxidation reaction from the electrode surface to a separate fuel tank. This approach decouples fuel feeding and electricity generation, providing greater operation flexibility and scalability for large-scale power generation applications. The DHPS-mediated ZAFC exhibited a superior peak power density of 0.51 W/cm2 and a continuous discharge capacity of 48.82 Ah with ZnO as the discharge product in the tank, highlighting its potential for power generation.

Synthesis of Indenones via Persulfate Promoted Radical Alkylation/Cyclization of Biaryl Ynones with 1,4-Dihydropyridines.

The oxidative radical cascade cyclization of alkynes has emerged as a versatile strategy for the efficient construction of diverse structural units and complex molecules in organic chemistry. This work reports an alkyl radical initiated 5-exo-trig cyclization of biaryl ynones with 1,4-dihydropyridines to selectively synthesize indenones.

Interfacial Synergy in Mo2C/MoC Heterostructure Promoting Sequential Polysulfide Conversion in High-Performance Lithium-Sulfur Battery.

A rational design of sulfur host is the key to conquering the"polysulfide shuttle effects" by accelerating the polysulfide conversion. Since the process involves solid-liquid-solid multistep phase transitions, purposely-engineered heterostructure catalysts with various active regions for catalyzing conversion steps correspondingly are beneficial to promote the overall conversion process. However, the functionalities of the materials surface and interface in heterostructure catalysts remain unclear. In this work, an Mo2C/MoC catalyst with abundant Mo2C surface-interface-MoC surface tri-active-region is developed by in situ converting the MoZn-metal organic framework. The experimental and simulation studies demonstrate the interface can catch long-chain polysulfides and promote their conversion. Instead, the Mo2C and MoC tend to accommodate the short-chain polysulfide and accelerate their conversion and the Li2S dissociation. Benefitting from the high catalytic ability, the Li-S battery assembled with the Mo2C/MoC-S cathode shows more discrete redox reactions and delivers a high initial capacity of 1603.6 mAh g-1 at 1 C charging-discharging rate, which is over twofolds of the one assembled using individual hosts, and 80.4% capacity can be maintained after 1000 cycles at 3 C rate. This work has demonstrated a novel synergy between the interface and material surface, which will help the future design of high-performance Li-S batteries.

JH degradation pathway participates in hormonal regulation of larval development of Bombyx mori following λ-cyhalothrin exposure.

λ-Cyhalothrin (λ-cyh), a widely utilized pyrethroid insecticide, poses serious threats to non-target organisms due to its persistence nature in the environment. Exposure to low concentrations of λ-cyh has been observed to result in prolonged larval development in Bombyx mori, leading to substantial financial losses in sericulture. The present study was undertaken to elucidate the underlying mechanisms for prolonged development caused by λ-cyh (LC10) exposure. The results showed that the JH Ⅲ titer was significantly increased at 24 h of λ-cyh exposure, and the JH interacting genes Methoprene-tolerant 2, Steroid Receptor Co-activator, Krüppel-homolog 1, and JH binding proteins were also up-regulated. Although the target of rapamycin (Tor) genes were induced by λ-cyh, the biosynthesis of JH in the corpora allata was not promoted. Notably, 13 JH degradation genes were found to be significantly down-regulated in the midgut of B. mori. The mRNA levels and enzyme activity assays indicated that λ-cyh had inhibitory effects on JH esterase, JH epoxide hydrolase, and JH diol kinase (JHDK). Furthermore, the suppression of JHDK (KWMTBOMO01580) was further confirmed by both western blot and immunohistochemistry. This study has offered a comprehensive perspective on the mechanisms underlying the prolonged development caused by insecticides, and our results also hold significant implications for the safe production of sericulture.

Accelerating Sulfur Redox Kinetics by Electronic Modulation and Drifting Effects of Pre-Lithiation Electrocatalysts.

Efficient catalyst design is crucial for addressing the sluggish multi-step sulfur redox reaction (SRR) in lithium-sulfur batteries (LiSBs), which are among the promising candidates for the next-generation high-energy-density storage systems. However, the limited understanding of the underlying catalytic kinetic mechanisms and the lack of precise control over catalyst structures pose challenges in designing highly efficient catalysts, which hinder the LiSBs' practical application. Here, drawing inspiration from the theoretical calculations, the concept of precisely controlled pre-lithiation SRR electrocatalysts is proposed. The dual roles of channel and surface lithium in pre-lithiated 1T'-MoS2 are revealed, referred to as the "electronic modulation effect" and "drifting effect", respectively, both of which contribute to accelerating the SRR kinetics. As a result, the thus-designed 1T'-Lix MoS2 /CS cathode obtained by epitaxial growth of pre-lithiated 1T'-MoS2 on cubic Co9 S8 exhibits impressive performance with a high initial specific capacity of 1049.8 mAh g-1 , excellent rate-capability, and remarkable long-term cycling stability with a decay rate of only 0.019% per cycle over 1000 cycles at 3 C. This work highlights the importance of precise control in pre-lithiation parameters and the synergistic effects of channel and surface lithium, providing new valuable insights into the design and optimization of SRR electrocatalysts for high-performance LiSBs.

Engineering FeCo Dual Sites on Tube-on-Plate Hollow Structure for Efficient Oxygen Electroreduction.

Atomically dispersed single-atom catalysts are intriguing catalysts in the field of electrocatalysis for nearly 100% exploitation of metal atoms. However, they are still far from practical usage due to the scaling relationship limit and metal loading limit. Generation of a diatomic complex would offer superior catalytic performance through the cooperation of two neighboring atoms as active sites. Herein, Fe/Co dual atomic sites embedded in a tube-on-plate hollow structure are designed and fabricated for an efficient electrochemical oxygen reduction reaction (ORR). The unique structure composed of ultrathin nanotube building blocks dramatically maximizes the surface area for copious active site exposure. Thanks to the synergetic interaction between Fe/Co pairs, the obtained FeCo/NC exhibits outstanding ORR activity and stability in alkaline media. Furthermore, density functional theory calculations have revealed that the remarkable activity is attributed to the electron-deficient Fe sites in FeCoN6. This work may pave the way for the innovative design of highly dispersed dual-site catalysts for broader applications in the realm of electrochemical catalysis.

Four-Chlorophenoxyacetic Acid Treatment Induces the Defense Resistance of Rice to White-Backed Planthopper Sogatella furcifera.

Chemical elicitors can increase plant defense against herbivorous insects and pathogens. The use of synthetic chemical elicitors is likely to be an alternative to traditional pesticides for crop pest control. However, only a few synthetic chemicals are reported to protect plants by regulating signaling pathways, increasing the levels of defense metabolites and interfering with insect feeding. Here, we found that the exogenous application of a phenoxycarboxylic compound, 4-chlorophenoxyacetic acid (4-CPA), can induce chemical defenses to protect rice plants from white-backed planthoppers (WBPH, Sogatella furcifera). Four-CPA was rapidly taken up by plant roots and degraded to 4-chlorophenol (4-CP). Four-CPA treatment modulated the activity of peroxidase (POD) and directly induced the deposition of lignin-like polymers using hydrogen peroxide (H2O2) as the electron acceptor. The polymers, which are thought to prevent the planthopper's stylet from reaching the phloem, were broken down by WBPH nymphs. Meanwhile, 4-CPA increased the levels of flavonoids and phenolamines (PAs). The increased flavonoids and PAs, together with the degradation product of the polymers, avoided nymphal feeding and prolonged the nymphal period for 1 day. These results indicate that 4-CPA has the potential to be used as a chemical elicitor to protect rice from planthoppers. Moreover, these findings also open a pathway for molecule structure design of phenoxycarboxylic compounds as chemical elicitors.

In vitro antibacterial effects of Broussonetia papyrifera leaf extract and its anti-colitis in DSS-treated mice.

Recently, the hybrid Broussonetia papyrifera (BP) has been extensively cultivated and predominantly utilized in ruminants because of its high protein and bioactive compound content. In the present study, the effects of an ethanolic extract of BP leaves (BPE, 200 mg/kg) on mitigating 2% dextran sodium sulfate (DSS)-induced intestinal inflammation in mice were evaluated. BPE is rich in flavonoids, polyphenols, and polysaccharides, and displays potent antioxidant and antibacterial activities against pathogenic strains such as Clostridium perfringens, Salmonella Typhimurium, and Salmonella enterica subsp. enterica in vitro. In a mouse study, oral administration of DSS resulted in weight loss, incidence of diarrhea, enlargement of the liver and spleen, impaired colonic morphology, downregulation of both gene and protein expression related to intestinal antioxidant (Nrf2) and barrier function (ZO-1), decreased diversity of colonic microbiota, and 218 differentially altered colonic metabolites; however, co-treatment with BPE did not restore these modified aspects except for the liver index and colonic bacterial diversity. The singular treatment with BPE did not manifest evident side effects in normal mice but induced a mild occurrence of diarrhea and a notable alteration in the colonic metabolite profile. Moreover, a single BPE administration augmented the abundance of the commensal beneficial bacteria Faecalibaculum and Akkermansia genera. Overall, the extract of BP leaves did not demonstrate the anticipated effectiveness in alleviating DSS-induced intestinal inflammation.

Association of liver function with health-related physical fitness: a cross-sectional study.

BACKGROUND: In this study, by analyzing the correlation between various components of health-related physical fitness (HPF) and liver function indicators, the indicators of physical fitness that were highly correlated with liver function and could be monitored at home were screened to prevent more serious liver disease in the future, and to provide experimental basis for prescribing personalized exercise. METHODS: A total of 330 faculties (female = 198) of a university were recruited. The indicators of HPF and liver function were measured. Spearman correlation analysis, multivariate linear regression, and cross-lagged panel model was used to data statistics. RESULTS: In males, body fat (BF) was positively correlated with alanine aminotransferase (ALT); vital capacity and the vital capacity index were positively correlated with albumin; and vertical jump was positively correlated with globulin and negatively correlated with the albumin-globulin ratio (P < 0.05). However, there was no significant correlation among all indicators controlled confounding factors. In females, BF was negatively correlated with direct bilirubin; VO2max was positively correlated with indirect bilirubin; and vertical jump was positively correlated with the albumin-globulin ratio and significantly negatively correlated with globulin (P < 0.05). Controlled confounding factors, body fat percentage was positively correlated with globulin (ß = 0.174) and negatively correlated with direct bilirubin (ß = -0.431), and VO2max was positively correlated with indirect bilirubin (ß = 0.238, P < 0.05). Cross-lagged panel analysis showed that BF percentage can negatively predict direct bilirubin levels with great significance (ß = -0.055, P < 0.05). CONCLUSIONS: HPF may play a crucial role in liver function screening, particularly for female faculty members. For males, BF, vertical jump, vital capacity and vital capacity index could be associated with liver function but are susceptible to complex factors such as age, smoking, diabetes, and hypertension. In females, BF percentage is an important predictor of abnormal liver function in addition to VO2max and vertical jump, which are not affected by complex factors.

Low concentration of indoxacarb interferes with the growth and development of silkworm by damaging the structure of midgut cells.

As an important economic insect, Bombyx mori plays an essential role in the development of the agricultural economy. Indoxacarb, a novel sodium channel blocker insecticide, has been widely used for the control of various pests in agriculture and forestry, and its environmental pollution caused by flight control operations has seriously affected the safe production of sericulture in recent years. However, the lethal toxicity and adverse effects of indoxacarb on silkworm remain largely unknown. In this study, the toxicity of indoxacarb on the 5th instar larvae of silkworm was determined, with an LC50 (72 h) of 2.07 mg/L. Short-term exposure (24 h) to a low concentration of indoxacarb (1/2 LC50) showed significantly reduced body weight and survival rate of silkworm larvae. In addition, indoxacarb also led to decreased cocoon weight and cocoon shell weight, but had no significant effects on pupation, adult eclosion, and oviposition. Histopathological and ultrastructural analysis indicated that indoxacarb could severely damage the structure of the midgut epithelial cells, and lead to physiological impairment of the midgut. A total of 3883 differentially expressed genes (DEGs) were identified by midgut transcriptome sequencing and functionally annotated using GO and KEGG. Furthermore, the transcription level and enzyme activity of the detoxification related genes were determined, and our results suggested that esterases (ESTs) might play a major role in metabolism of indoxacarb in the midgut of B. mori. Future studies to examine the detoxification or biotransformation function of candidate genes will greatly enhance our understanding of indoxacarb metabolism in B. mori. The results of this study provide a theoretical basis for elucidating the mechanism of toxic effects of indoxacarb on silkworm by interfering with the normal physiological functions of the midgut.

Predictive value of radiomics analysis of enhanced CT for three-tiered microvascular invasion grading in hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is a major risk factor, for recurrence and metastasis of hepatocellular carcinoma (HCC) after radical surgery and liver transplantation. However, its diagnosis depends on the pathological examination of the resected specimen after surgery; therefore, predicting MVI before surgery is necessary to provide reference value for clinical treatment. Meanwhile, predicting only the existence of MVI is not enough, as it ignores the degree, quantity, and distribution of MVI and may lead to MVI-positive patients suffering due to inappropriate treatment. Although some studies have involved M2 (high risk of MVI), majority have adopted the binary classification method or have not included radiomics. PURPOSE: To develop three-class classification models for predicting the grade of MVI of HCC by combining enhanced computed tomography radiomics features with clinical risk factors. METHODS: The data of 166 patients with HCC confirmed by surgery and pathology were analyzed retrospectively. The patients were divided into the training (116 cases) and test (50 cases) groups at a ratio of 7:3. Of them, 69 cases were MVI positive in the training group, including 45 cases in the low-risk group (M1) and 24 cases in the high-risk group (M2), and 47 cases were MVI negative (M0). In the training group, the optimal subset features were obtained through feature selection, and the arterial phase radiomics model, portal venous phase radiomics model, delayed phase radiomics model, three-phase radiomics model, clinical imaging model, and combined model were developed using Linear Support Vector Classification. The test group was used for validation, and the efficacy of each model was evaluated through the receiver operating characteristic curve (ROC). RESULTS: The clinical imaging features of MVI included alpha-fetoprotein, tumor size, tumor margin, peritumoral enhancement, intratumoral artery, and low-density halo. The area under the curve (AUC) of the ROC values of the clinical imaging model for M0, M1, and M2 were 0.831, 0.701, and 0.847, respectively, in the training group and 0.782, 0.534, and 0.785, respectively, in the test group. After combined radiomics analyis, the AUC values for M0, M1, and M2 in the test group were 0.818, 0.688, and 0.867, respectively. The difference between the clinical imaging model and the combined model was statistically significant (p = 0.029). CONCLUSION: The clinical imaging model and radiomics model developed in this study had a specific predictive value for HCC MVI grading, which can provide precise reference value for preoperative clinical diagnosis and treatment. The combined application of the two models had a high predictive efficacy.

Rejuvenation of aged graphite anodes from spent lithium-ion batteries via a facile surface treatment strategy.

In this study, we present a facile formic acid treatment to rejuvenate aged graphite anodes from spent lithium-ion batteries (LIBs) without damaging the electrode structure. This method effectively removes the interfacial blocking layer, improving capacity and rate performance. Our approach contributes to sustainable battery recycling strategies for spent graphite anodes in LIBs.

On-line screening and verification of haptens in Xiangdan injection combining chemical analysis with activity detection.

Xiangdan injection (XDI), as a well-known traditional Chinese medicine injection, is of great significance to treat cardiovascular and cerebrovascular diseases. The haptens causing allergic reactions are urged to be detected due to the adverse reaction. In this study, an efficient approach was established to rapidly identify and screen potential haptens in XDI for the first time by combining high performance liquid chromatography-diode array detector-electrospray ionization-ion trap-time of flight-mass spectrometry with human serum albumin-fluorescence detector (HPLC-DAD-ESI-IT-TOF-MS-HSA-FLD). 21 compounds were identified according to their mass spectrum or comparison with reference substances and 8 salvianolic acids in XDI showed interactions with HSA in varying degrees. After that, surface plasmon resonance (SPR) was applied to screen the compounds showing specific affinity with human serum albumin (HSA). Subsequently, active systemic anaphylaxis (ASA) in guinea pigs was carried out to verify the sensitization of active compounds, In the meantime the serum IgE level before and after challenge was measured by the enzyme-linked immunosorbent assay (ELISA). Ultimately, it was tested that salvianolic acid C had a strong sensitization, in addition, lithospermic acid, rosmarinic acid and salvianolic acid B had potential sensitization. This study suggest that the on-line method provides rapid preliminary searching for haptens in XDI, combined with SPR and ASA, offering an efficient, rapid and comprehensive approach to screen haptens.

Characterization of the sublethal toxicity and transcriptome-wide biological changes induced by λ-cyhalothrin in Bombyx mori.

λ-Cyhalothrin (λ-cyh) is widely used in agricultural production and has been reported to cause damages to numerous nontarget insects. As an important economic and model insect of Lepidoptera, Bombyx mori was extremely sensitive to λ-cyh, and pesticide drift often leads to silkworm poisoning. However, little is known about the persistence of sublethal effects or the potential recovery from short-term exposure to sublethal doses of pesticides. In this study, we estimated the sublethal effects caused by short-term exposure (24 h) of λ-cyh LC1 , LC10 , LC25 , and LC50 , respectively, and investigated the persistent negative effects on the growth, survival, and pupal metamorphosis of silkworm larvae. Silkworm growth was mostly retarded after λ-cyh exposure, with dose-dependent recovery observed at delayed time points. Relative to the control, the treatment groups showed significantly higher larval mortalities and abnormal pupa rates. Additionally, transcriptome sequencing was conducted to investigate the effects of λ-cyh LC10 on the normal physiological functions in the midgut of B. mori. A total of 2697 differentially expressed genes were identified, and 57.1% of DEGs were down-regulated. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis further revealed that energy and nutrient metabolisms were negatively affected. Moreover, we demonstrated that sublethal λ-cyh inhibited the oxidative phosphorylation pathway by reducing the expression of mitochondrial electron transport chain complex genes and consequently the synthesis of ATP. This study has provided useful transcriptome-wide expression resources to facilitate the overall knowledge of the molecular basis of sublethal toxicity caused by λ-cyh in the midgut of B. mori.

Inorganic carbon utilization: A target of silver nanoparticle toxicity on a submerged macrophyte.

Submerged macrophytes play an important role in the global carbon cycle through diversified pathways of inorganic carbon (Ci) utilization distinct from terrestrial plants. However, the effects of silver nanoparticles (AgNPs), an emerging contaminant, were unknown on the Ci utilization of submerged macrophytes. In Ottelia alismoides, the only known submerged macrophyte with three pathways of Ci utilization, before absorption, AgNPs inhibited the external carbonic anhydrase activity thus reducing the capacity of the plant to use HCO3-. After entering the plant, AgNPs mainly aggregated at the cell wall and in the chloroplast. The internalized AgNPs inhibited ribulose 1,5-bisphosphate carboxylase-oxygenase (Rubisco) activity blocking CO2 fixation and disturbed C4 and crassulacean acid metabolism (CAM) by inhibiting phosphoenolpyruvate carboxylase (PEPC), pyruvate phosphate dikinase (PPDK), and NAD-dependent malic enzyme (NAD-ME) activities to alter intracellular malate biosynthesis and decarboxylation. Overall, our findings indicate that the Ci utilization of the submerged macrophyte is a target of AgNPs toxicity that might affect the carbon cycle in aquatic systems.

Effects of Fiber Type on the Mechanical Properties of the Open-Graded Friction Course Mixture.

The open-graded friction courses (OGFCs) have a large number of interconnected voids, which may cause serious water damage to the pavement. Hence, the road performance needs to be investigated. In this study, the mechanical properties of OGFCs containing two different fibers (lignin and mineral fiber) were investigated. Based on the procedure proposed by the Chinese specification JTG F40-2004, OGFCs were designed with the asphalt content between 4.1 and 4.7 wt % to find the optimal asphalt content (OAC). The mesh-basket draindown test was used to check the fiber's stabilization and absorption of bitumen. OGFCs containing the lignin/mineral fiber with OAC would be preferred in terms of the bulk specific gravity. These results indicate that the fiber can bring higher air voids to the OGFCs, and the different specific gravities of fibers may primarily account for the result. Both the lignin and mineral fibers can bring much more asphalts padded in the pores of mineral aggregates and subsequently larger OAC in OGFCs due to their higher asphalt absorption. Performance experiments were carried out to check the dynamic stability and moisture susceptibility of OGFCs containing the lignin/mineral fiber. The study suggests that the lignin and mineral fiber can be used to adjust the internal environment of OGFCs, enhancing the moisture damage resistance and improving the rutting resistance of OGFCs at high temperatures.

A selection marker-free method for gene deletion and editing in baculovirus genomes.

Here, we develop a simple, efficient, bacmid-based, selection marker-free method for gene deletion and editing in baculovirus genomes. Specifically, based on pFastbac1, a donor plasmid with long left and right homology arms but without a reporter was constructed for disrupting ie1, an essential baculovirus gene. Instead of ligating with a plasmid, the homology arms were introduced to the polyhedrin locus of BmNPV bacmid using the BmNPV bac-to-bac expression system. Two viruses generated from the modified bacmid and unmodified BmNPV bacmid were then used to co-infect BmN cells in order that recombination takes place at the ie1 locus between them. Finally, without multiple rounds of purification, total cellular DNA was isolated, transformed into Cacl2-treated competent DH10B cells, and then blue colonies were selected for PCR screening. Remarkably, the proportion of blue colonies containing ie1-disrupted bacmid was found to be around 7 %. Moreover, using primers flanking the homology arms further confirmed that all these positive recombinants were double crossovers. These findings indicate that our method is also capable of gene modification if inverse PCR or seamless cloning is used to construct the donor plasmid and sequencing is employed to select positive colonies.

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and D-galactose induced senescent cells.

The nicotinamide adenine dinucleotide (NAD+) level shows a temporal decrease during the aging process, which has been deemed as an aging hallmark. Nicotinamide mononucleotide (NMN), a key NAD+ precursor, shows the potential to retard the age-associated functional decline in organs. In the current study, to explore whether NMN has an impact on the intestine during the aging process, the effects of NMN supplementation on the intestinal morphology, microbiota, and NAD+ content, as well as its anti-inflammatory, anti-oxidative and barrier functions were investigated in aging mice and D-galactose (D-gal) induced senescent IPEC-J2 cells. The results showed that 4 months of NMN administration had little impact on the colonic microbiota and NAD+ content in aging mice, while it significantly increased the jejunal NAD+ content and improved the jejunal structure including increasing the villus length and shortening the crypt. Moreover, NMN supplementation significantly up-regulated the mRNA expression of SIRT3, SIRT6, nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), the catalytic subunit of glutamate-cysteine ligase (GCLC), superoxide dismutase 2 (SOD2), occludin, and claudin-1, but down-regulated the mRNA expression of tumor necrosis factor alpha (TNF-α). Specifically, in the D-gal induced senescent IPEC-J2 cells, 500 µM NMN restored the increased mRNA expression of interleukin 6 (IL6ST), IL-1A, nuclear factor (NF-κB1), and claudin-1 to normal levels to some extent. Furthermore, NMN treatment significantly affected the mRNA expression of antioxidant enzymes including NQO1, GCLC, SOD 2 and 3, and GSH-PX1, 3 and 4. In addition, 200 µM NMN enhanced the cell viability and total antioxidant capacity and lowered the reactive oxygen species level of senescent IPEC-J2 cells. Notably, NMN restored the down-regulated protein expression of occludin and claudin-1 induced by D-gal. The above data demonstrated the potential of NMN in ameliorating the structural and functional decline in the intestine during aging.