Dual interfaces and confinements on Fe2N@Fe3O4/VN heterojunction toward high-efficient lithium storage.

Ferroferric oxide (Fe3O4) as an anode material of lithium-ion battery has been widely investigated due to its high theoretical capacity, environmental friendliness, natural abundance, and low cost. However, it suffers from severe aggregation and volume expansion during energy storage. Herein, we rationally construct an advanced Fe2N@Fe3O4/VN heterostructure via a hydrothermal and followed nitridation process, where the wrapping of conductive Fe2N on the surface of Fe3O4 effectively improves the electron conductivity and alleviates the volume expansion, and VN inhibits the agglomeration of Fe2N@Fe3O4. Benefiting from the dual conductive confinements and promoted interfacial charge transfer, the Fe2N@Fe3O4/VN heterojunction exhibits excellent rate capability and cycling stability. It possesses the highest reversible capacity of 420.8 mAh g-1 at 1 A g-1 after 600 cycles, which is three times that of Fe3O4. Furthermore, a full cell based on a Fe2N@Fe3O4/VN anode and a LiFePO4 cathode delivers considerable electrochemical performance. This work demonstrates that Fe2N@Fe3O4/VN is a potential anode material and provides a model in constructing other high-performance electrode materials.

Chronic stress promotes colorectal cancer progression by enhancing glycolysis through ß2-AR/CREB1 signal pathway.

Colorectal cancer (CRC) is a common malignancy worldwide, and chronic stress has been considered as a significant risk factor for CRC. However, the role of chronic stress in CRC progression is unclear. The present study showed that pre-exposure to chronic stress facilitated CRC tumor growth in mice, and epinephrine promoted CRC cell proliferation in vitro. Metabolomics analysis revealed that chronic stress reshaped metabolic pathways to enhance glycolysis. Additional studies have shown that stress enhanced the expression levels of glycolytic-associated enzymes, including GLUT1, HK2 and PFKP. Mechanistically, chronic stress activated the ß2-AR/PKA/CREB1 pathway, as a result, phosphorylated CREB1 transcriptional induced glycolytic enzymes expression. Furthermore, stress-induced cell proliferation and tumor growth could be reversed by administration of glycolysis inhibitor 2-deoxyglucose (2-DG) and ß2-AR antagonist ICI118,551, respectively. Altogether, these findings define novel insights into the stress-induced epinephrine-mediated CRC progression from the point of view of tumor energy metabolism reprogramming and provide a perspective on targeting glycolysis as a potential approach in stress-associated CRC treatment.

Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Regulating d-Band Center of Ti2 C MXene Via Nb Alloying for Stable and High-Efficient Supercapacitive Performances.

Ti2 C MXene with the lowest formula weight is expected to gain superior advantages in gravimetric capacitances over other heavier MXenes. Nevertheless, its poor chemical and electrochemical stability is the most fatal drawback and seriously hinders its practical applications. Herein, an alloy engineering strategy at the transition metal-sites of Ti2 C MXene is proposed. Theoretical calculations reveal that the electronic redistribution of the solid-solution TiNbC MXene improves the electronic conductivity, induces the upward d-band center, tailors the surface functional groups, and increases the electron loss impedance, resulting in its excellent capacitive performance and high chemical stability. The as-prepared flexible TiNbC film delivers specific capacitance up to 381 F g-1 at a scan rate of 2 mV s-1 and excellent electrochemical stability without capacitance loss after 10000 charge/discharging cycles. This work provides a universal approach to develop high-performance and chemically stable MXene electrodes.

Two-Dimensional Ordered Double-Transition Metal Carbides for the Electrochemical Nitrogen Reduction Reaction.

The electrochemical nitrogen reduction reaction (NRR) provides a green and sustainable strategy as an alternative to the Haber-Bosch process. The development of electrocatalysts with low overpotential, high selectivity, and fast reaction kinetics remains a significant challenge. Here, density functional theory computations are carried out to systematically predict the prospect of 18 two-dimensional (2D) ordered double-transition metal carbides (MXenes) as NRR electrocatalysts. Our results revealed that the basal plane of Mo2Nb2C3 MXene exhibited the most outstanding catalytic activity while effectively suppressed the hydrogen evolution reaction with an overpotential of 0.48 V. The exposed Mo3 moiety moderately regulating the electron transfer between reaction intermediates is answerable for the high activity. Finally, our finding broadens the horizon of 2D materials as NRR electrocatalysts.

Distribution of Nicotinamide Mononucleotide after Intravenous Injection in Normal and Ischemic Stroke Mice.

OBJECTIVE: This study determined for the first time the distribution of intravenous nicotinamide mononucleotide (NMN) and its metabolite nicotinamide adenine dinucleotide (NAD) in normal and ischemic stroke mice, examined the therapeutic effect of NMN on ischemic brain infarction, and evaluated acute toxicity of NMN after intravenous injection of NMN. METHODS: NMN and NAD levels were determined using ultra-high-performance liquid chromatography tandem mass spectrometry in biological samples from mice with or without middle cerebral artery occlusion (MCAO) at different time points post intravenous NMN injection (300 mg/kg). Brain infarction was evaluated 24 h post-MCAO. 2 g/kg NMN was used in the acute toxicity test. RESULTS: Under either normal or MCAO conditions, serum NMN levels sharply increased after intravenous NMN administration and then decreased rapidly within 15 min, while serum NAD levels remained unchanged during 30 min observation. Both substances displayed tissue accumulation over time and stored faster under MCAO conditions, with kidney having the highest concentrations. Particularly, NMN accumulated earlier than NAD in the brain. Moreover, NMN reduced cerebral infarction at 24 h post-MCAO. No acute toxicity was observed for 14 days. NRK1 and SLC12A8 involved in two pathways of NMN uptake exhibited the highest expressions in kidney and colon, respectively, among 11 different tissues. CONCLUSION: NMN distributes to various tissues after intravenous injection and has the ability to enter the brain to boost NAD levels, and exhibits safety and therapeutic effect on acute ischemic stroke injury. High renal distribution of NMN indicates its importance in the kidney.

Ginsenosides in cancer: A focus on the regulation of cell metabolism.

Metabolic alterations play a key role in promoting tumor initiation and progression, leading to extensive tumor heterogeneity and adaptability. Thus, targeting abnormal metabolic processes is a promising novel approach for cancer treatment. Numerous pharmacological studies have indicated that many traditional Chinese medicines possess remarkable antitumor activities. Ginsenosides, the main bioactive ingredients of Panax and other types of ginseng, exert beneficial antitumor effects, in addition to the anti-inflammation, anti-oxidant, and anti-fatigue effects. Recently, considerable attention has been paid to the regulation of cancer cell metabolism by ginsenosides. Here, we summarize the structural characteristics and classification of ginsenosides, their antitumor mechanisms, recent progress and the achievements of ginsenoside research in modulating cancer cell metabolism, including the diverse metabolic processes and their regulatory processes, as well as the opportunities and challenges of strategies targeting metabolic vulnerabilities. This review provides novel perspectives on the potential applications of ginsenosides that exert antitumor effects by reshaping cancer metabolism.

Preliminary prediction of semen quality based on modifiable lifestyle factors by using the XGBoost algorithm.

Introduction: Semen quality has decreased gradually in recent years, and lifestyle changes are among the primary causes for this issue. Thus far, the specific lifestyle factors affecting semen quality remain to be elucidated. Materials and methods: In this study, data on the following factors were collected from 5,109 men examined at our reproductive medicine center: 10 lifestyle factors that potentially affect semen quality (smoking status, alcohol consumption, staying up late, sleeplessness, consumption of pungent food, intensity of sports activity, sedentary lifestyle, working in hot conditions, sauna use in the last 3 months, and exposure to radioactivity); general factors including age, abstinence period, and season of semen examination; and comprehensive semen parameters [semen volume, sperm concentration, progressive and total sperm motility, sperm morphology, and DNA fragmentation index (DFI)]. Then, machine learning with the XGBoost algorithm was applied to establish a primary prediction model by using the collected data. Furthermore, the accuracy of the model was verified via multiple logistic regression following k-fold cross-validation analyses. Results: The results indicated that for semen volume, sperm concentration, progressive and total sperm motility, and DFI, the area under the curve (AUC) values ranged from 0.648 to 0.697, while the AUC for sperm morphology was only 0.506. Among the 13 factors, smoking status was the major factor affecting semen volume, sperm concentration, and progressive and total sperm motility. Age was the most important factor affecting DFI. Logistic combined with cross-validation analysis revealed similar results. Furthermore, it showed that heavy smoking (>20 cigarettes/day) had an overall negative effect on semen volume and sperm concentration and progressive and total sperm motility (OR = 4.69, 6.97, 11.16, and 10.35, respectively), while age of >35 years was associated with increased DFI (OR = 5.47). Conclusion: The preliminary lifestyle-based model developed for semen quality prediction by using the XGBoost algorithm showed potential for clinical application and further optimization with larger training datasets.

Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear. PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms. METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored. RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling. CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.

Effects of the E1 activating enzyme UBA2 on porcine oocyte maturation, apoptosis, and embryonic development in vitro.

The purpose of this study was to investigate the effect of the E1 activating enzyme UBA2 on the expression of the SUMO-1 protein during in vitro maturation (IVM) of pig oocytes and embryonic development. In the 5 µg/ml UBA2 treatment group, the expression of the anti-apoptotic gene Bcl-2 and the embryo cleavage rate was significantly increased, while the proapoptotic gene Bax was significantly reduced. When 10 µg/ml UBA2 was added, the in vitro maturation rate, blastocyst rate, and SUMO-1 protein content of oocytes increased significantly (p < .05), and the expression of proapoptotic gene Caspase3 was significantly decreased (p < .05), while the viability of cumulus cells was extremely significantly reduced (p < .01). In summary, UBA2 can regulate the content of the SUMO-1 protein in mature pig oocytes in vitro, which in turn affects the maturation rate of oocytes, expression of apoptosis genes, cumulus cell viability, and the development of embryos after fertilization.

Effects of E2 binding enzyme UBC9 on porcine oocyte maturation, apoptosis and embryo development.

SUMOylation is a dynamic post-translational modification process. However, the function of small ubiquitin-like modifiers (SUMOs) in the maturation of porcine oocytes and embryo growth is not well known. Therefore, the aim of this study was to investigate the effect of E2 binding enzyme UBC9 on the expression of SUMO-1 protein during the in vitro maturation of porcine oocytes and embryo development after in vitro fertilization. Four groups were used: 0 (Control), 5, 10 and 15 µg/ml UBC9. Western blotting, flow cytometry and RT-qPCR were used to detect the in vitro maturation of porcine oocytes, SUMO-1 content, viability and the expression of apoptotic genes. Compared to those in the control treatment, the maturation rate (p < .05) and viability (p < .01) of oocytes in the 5 µg/ml treatment group decreased significantly. SUMO-1 protein markers appeared at 59 and 71 kDa and the content of SUMO-1 protein in the 10 µg/ml treatment group decreased significantly (p < .05). In the expression of apoptosis-related genes, Bcl-2 gene expression was significantly downregulated in the 10 µg/ml treatment group (p < .05). However, Bax and Caspase-3 were significantly upregulated in the 5 µg/ml treatment group (p < .05). During embryonic development, the cleavage rate of oocytes in the 10 µg/ml treatment group was significantly reduced (p < .05), whereas blastocyst formation rate in the 5 µg/ml treatment group was significantly reduced. UBC9 regulates SUMO-1 content in mature pig oocytes in vitro, which affects oocyte maturation rate, viability, apoptotic genes expression and embryo development after fertilization.

Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Orphan nuclear receptor Nur77, which is low expressed in HCC, functions as a tumor suppressor to suppress HCC. However, the detailed mechanism is still not well understood. Here, we demonstrate that Nur77 could inhibit HCC development via transcriptional activation of the lncRNA WAP four-disulfide core domain 21 pseudogene (WFDC21P). Nur77 binds to its response elements on the WFDC21P promoter to directly induce WFDC21P transcription, which inhibits HCC cell proliferation, tumor growth, and tumor metastasis both in vitro and in vivo. In clinical HCC samples, WFDC21P expression positively correlated with that of Nur77, and the loss of WFDC21P is associated with worse prognosis. Mechanistically, WFDC21P could inhibit glycolysis by simultaneously interacting with PFKP and PKM2, two key enzymes in glycolysis. These interactions not only abrogate the tetramer formation of PFKP to impede its catalytic activity but also prevent the nuclear translocation of PKM2 to suppress its function as a transcriptional coactivator. Cytosporone-B (Csn-B), an agonist for Nur77, could stimulate WFDC21P expression and suppress HCC in a WFDC21P-dependent manner. Therefore, our study reveals a new HCC suppressor and connects the glycolytic remodeling of HCC with the Nur77-WFDC21P-PFKP/PKM2 axis.

The Role of Cell Growth-Related Gene Copy Number Variation in Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) is a recurrent and refractory clinical endocrine disease. Some studies have shown that the incidence of AITD is not only related to iodine, a kind of environmental factor, but that susceptibility genes also play a crucial role in its pathogenesis. Since research on susceptibility genes is still underway, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related to susceptibility to AITD, and to explore the risk factors in the occurrence of AITD. Blood samples from five AITD patients and five controls from each area were assessed by chromosome microarray to identify candidate genes. The copy number (CN) of the candidate genes and urinary iodine levels were determined in adults, including 158 AITD patients and 181 controls, from areas having different iodine statuses. The cell growth-related genes, glypican 5 (GPC5), B9 domain containing 2 (B9D2), and ankyrin repeat and suppressor of cytokine signaling [SOCS] box-containing protein family 11 (ASB11), were selected as the candidate genes. The distribution of GPC5, B9D2, and ASB11 CNVs in AITD patients and controls was significantly different, and high urinary iodine levels and GPC5 CNVs are risk factors for AITD. There was no significant association between urinary iodine level and CNVs of the candidate genes. High urinary iodine levels and GPC5 CNVs are risk factors for AITD, but an association with the occurrence of AITD was not found.

Copy Number Variation of Immune-Related Genes and Their Association with Iodine in Adults with Autoimmune Thyroid Diseases.

BACKGROUND: Autoimmune thyroid diseases (AITD) are complex conditions that are caused by an interaction between genetic susceptibility and environmental triggers. Iodine is already known to be an environmental trigger for AITD, but genes associated with susceptibility need to be further assessed. Therefore, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related with susceptibility to AITD, and to investigate the interaction between iodine status and CNVs in the occurrence of AITD. METHODS: Blood samples from 15 patients with AITD and 15 controls were assessed by chromosome microarray to identify candidate genes. The copy number of candidate genes and urinary iodine level was determined in adults from areas of different iodine statuses including 158 patients and 181 controls. RESULTS: The immune-related genes, SIRPB1 and TMEM91, were selected as candidate genes. The distribution of SIRPB1 CNV in AITD patients and controls was significantly different and was considered a risk factor for AITD. There was no significant association between urinary iodine level and candidate gene CNVs. CONCLUSION: SIRPB1 CNV and an excess of iodine were risk factors for AITD, but an association with the occurrence of AITD was not found.

Association of TSHR Gene Copy Number Variation with TSH Abnormalities.

Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. By consulting the literature, we found that the TSHR, PAX8, and PDE4B genes are associated with thyroid function. Recently, copy number variations (CNVs) have been used as genetic markers to investigate inter-individual variation. Therefore, we investigated the relationship between the TSHR, PAX8, and PDE4B gene CNVs and TSH abnormalities, by calculating variations in gene copy number. Four hundred and eighty-one participants, 232 healthy controls and 249 patients with TSH abnormalities, were selected from three distinct areas in China with different iodine statuses. RT-PCR was used to detect CNVs. Urinary iodine concentrations (UIC) were measured by As3+-Ce4+ catalytic spectrophotometry. There was an association between a CNV at the TSHR gene and TSH abnormalities (p = 0.002). The distribution of PAX8 and PDE4B gene CNVs between patients with TSH abnormalities and healthy controls was not significantly different. UIC > 200 µg/l (OR = 1.49, 95% CI = 1.01-2.22) and the TSHR gene (OR = 6.01, 95% CI = 1.96-18.41) were found to be risk factors for TSH abnormalities. PAX8 and PDE4B gene CNVs were not significantly associated with TSH abnormalities. There was no significant interaction between UIC and any of the examined CNVs. In conclusion, the TSHR gene CNV was associated with the development of TSH abnormalities. No significant associations were revealed between urinary iodine levels and candidate gene CNVs.

Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation.

Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPß, a rate-limiting enzyme in FAO. Although TPß activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPß association results in Nur77 self-sacrifice to protect TPß from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPß interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.

The application of serum iodine in assessing individual iodine status.

CONTEXT: The prevalence of thyroid disease in China is on the rise, and this could be partly associated with excessive iodine intake in some individuals; therefore, increased attention is being paid to individual iodine status. However, current indices are not appropriate for evaluating individual iodine status. OBJECTIVE: To evaluate the association between serum iodine and urinary iodine (UI), as well as thyroid diseases, and provide an excellent base for future individual iodine status assessment. DESIGN, SUBJECTS AND MEASUREMENTS: A total of 902 adults were enrolled in this study including 325, 286 and 291 subjects from regions in China where iodine is adequate, sufficient and in excess, respectively. Serum iodine, UI and thyroid function were assessed, and ultrasonography performed in all subjects. RESULTS: The median serum iodine values of adults with subclinical hypothyroidism, high serum autoantibody and thyroid nodules were significantly higher than those of euthyroid adults (P<0.05). A serum iodine level higher than 100 µg/L was considered as a risk factor for thyroid diseases. Serum iodine had strong nonlinear correlations with UI and thyroid function. When thyroid function was taken as a gold standard, the area under the receiver operating characteristic (ROC) curve for serum iodine was 0.752 and UI was 0.507 for subjects with lower serum iodine and UI levels. The area for serum iodine was 0.773 and UI was 0.638 for subjects with higher serum iodine and UI levels. The areas under these curves were significantly different (P<0.001). CONCLUSION: In adults, serum iodine had a strong nonlinear correlation with UI and a high level of serum iodine was a risk factor for thyroid diseases.

Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway.

Replenishment of NAD+ has been shown to protect against brain disorders such as amyotrophic lateral sclerosis and ischemic stroke. However, whether this intervention has therapeutic effects in intracerebral hemorrhage (ICH) is unknown. In this study, we sought to determine the potential therapeutic value of replenishment of NAD+ in ICH. In a collagenase-induced ICH (cICH) mouse model, nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis, was administrated at 30 minutes post cICH from tail vein to replenish NAD+. NMN treatment did not decrease hematoma volume and hemoglobin content. However, NMN treatment significantly reduced brain edema, brain cell death, oxidative stress, neuroinflammation, intercellular adhesion molecule-1 expression, microglia activation and neutrophil infiltration in brain hemorrhagic area. Mechanistically, NMN enhanced the expression of two cytoprotective proteins: heme oxygenase 1 (HO-1) and nuclear factor-like 2 (Nrf2). Moreover, NMN increased the nuclear translocation of Nrf2 for its activation. Finally, a prolonged NMN treatment for 7 days markedly promoted the recovery of body weight and neurological function. These results demonstrate that NMN treats brain injury in ICH by suppressing neuroinflammation/oxidative stress. The activation of Nrf2/HO-1 signaling pathway may contribute to the neuroprotection of NMN in ICH.

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3-A20 in Ischemic Stroke.

AIM: NAMPT is a novel therapeutic target of ischemic stroke. The aim of this study was to investigate the effect of a potential NAMPT activator, P7C3-A20, an aminopropyl carbazole derivative, on ischemic stroke. METHODS: In vitro study, neuron protection effect of P7C3-A20 was investigated by co-incubation with primary neurons subjected to oxygen-glucose deprivation (OGD) or oxygen-glucose deprivation/reperfusion (OGD/R) injury. In vivo experiment, P7C3-A20 was administrated in middle cerebral artery occlusion (MCAO) rats and infarct volume was examined. Lastly, the brain tissue nicotinamide adenine dinucleotide (NAD) levels were detected in P7C3-A20 treated normal or MCAO mice. RESULTS: Cell viability, morphology, and Tuj-1 staining confirmed the neuroprotective effect of P7C3-A20 in OGD or OGD/R model. P7C3-A20 administration significantly reduced cerebral infarction in MCAO rats. Moreover, brain NAD levels were elevated both in normal and MCAO mice after P7C3-A20 treatment. CONCLUSIONS: P7C3-A20 has neuroprotective effect in cerebral ischemia. The study contributes to the development of NAMPT activators against ischemic stroke and expands the horizon of the neuroprotective effect of aminopropyl carbazole chemicals.