Harmine inhibits the proliferation and migration and promotes the apoptosis of colon cancer cells via inhibition of the FAK/AKT and ERK1/2/CREB signaling pathways.

Harmine is present in a variety of medicinal plants, and its effects on colon cancer cells remain unclear. Here, we found that harmine exhibited significant inhibitory effects on the proliferation of colon cancer cells by inhibiting the phosphorylation levels of the FAK/AKT and ERK1/2/CREB. Furthermore, harmine also inhibited the migration of colon cancer cells and suppressed the expression levels of MMP-2, MMP-9, and VEGF. Additionally, harmine-induced apoptosis in colon cancer cells by regulating the expression of Bcl-2 and Bax. In conclusion, our findings suggest that harmine exerts a significant inhibitory effect on the development of colon cancer cells.

[Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases].

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

The role of galectins in the regulation of autophagy and inflammasome in host immunity.

Galectins, a family of glycan-binding proteins have been shown to bind a wide range of glycans. In the cytoplasm, these glycans can be endogenous (or "self"), originating from damaged endocytic vesicles, or exogenous (or "non-self"), found on the surface of invading microbial pathogens. Galectins can detect these unusual cytosolic exposures to glycans and serve as critical regulators in orchestrating immune responses in innate and adaptive immunity. This review provides an overview of how galectins modulate host cellular responses, such as autophagy, xenophagy, and inflammasome-dependent cell death program, to infection.

Long-life triclosan exposure induces ADHD-like behavior in rats via prefrontal cortex dopaminergic deficiency.

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

Hierarchical Supramolecular Aggregation of Molecular Nanoparticles for Granular Materials with Ultra High-Speed Impact-Resistance.

The high-speed impact-resistanct materials are of great significance while their development is hindered by the intrinsic tradeoff between mechanical strength and energy dissipation capability. Herein, the new chemical system of molecular granular material (MGM) is developed for the design of impact-resistant materials from the supramolecular complexation of sub-nm molecular clusters (MCs) and hyper-branched polyelectrolytes. Their hierarchical aggregation provides the origin of the decoupling of mechanical strengths and structural relaxation dynamics. The MCs' intrinsic fast dynamics afford excellent high-speed impact-resistance, up to 5600 s-1 impact in a typical split-Hopkinson pressure bar test while only tiny boundary cracks can be observed even under 7200 s-1 impact. The high loadings of MCs and their hierarchical aggregates provide high-density sacrificial bonding for the effective dissipation of the impact energy, enabling the protection of fragile devices from the direct impact of over 200 m s-1 bullet. Moreover, the MGMs can be conveniently processed into protective coatings or films with promising recyclability due to the supramolecular interaction feature. The research not only reveals the unique relaxation dynamics and mechanical properties of MGMs in comparison with polymers and colloids, but also develops new chemical systems for the fabrication of high-speed impact-resistant materials.

Galectin-3 contributes to pathogenesis of IgA nephropathy.

IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous "grouped" ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease.

TAR RNA selective targeting ruthenium(II) complexes as HIV-1 reverse transcriptase inhibitors: On exploring structure-activity relationships of multiple positions.

HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R1 and R3 groups. The most potent and selective TAR RNA binder was a3 with R1 = OH, R2 = H and R3 = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.

Epinephelus coioides Sec3 promotes Singapore grouper iridovirus infection by negatively regulates immune response.

Exocyst, a protein complex, plays a crucial role in various cellular functions, including cell polarization, migration, invasion, cytokinesis, and autophagy. Sec3, known as Exoc1, is a key subunit of the Exocyst complex and can be involved in cell survival and apoptosis. In this study, two subtypes of Sec3 were isolated from Epinephelus coioides, an important marine fish in China. The role of E. coioides Sec3 was explored during Singapore grouper iridovirus (SGIV) infection, an important pathogen of marine fish which could induce 90 % mortality. E. coioides Sec3 sequences showed a high similarity with that from other species, indicating the presence of a conserved Sec3 superfamily domain. E. coioides Sec3 mRNA could be detected in all examined tissues, albeit at varying expression levels. SGIV infection could upregulate E. coioides Sec3 mRNA. Upregulated Sec3 significantly promoted SGIV-induced CPE, and the expressions of viral key genes. E. coioides Sec3 could inhibit the activation of NF-κB and AP-1, as well as SGIV-induced cell apoptosis. The results illustrated that E. coioides Sec3 promotes SGIV infection by regulating the innate immune response.

[Characteristics of Soil Organic Carbon and Its Influencing Factors of Different Plant Communities in the Yellow River Delta].

Changes in soil organic carbon （SOC） are of great importance to the evolution of soil quality. The distribution characteristics of soil organic carbon （SOC）, easily oxidizable organic carbon （EOC）, dissolved organic carbon （DOC）, and particulate organic carbon （POC） were investigated in the 0-50 cm soil layer of the Phragmites australis, Suaeda salsa, and Tamarix chinensis communities of the supratidal zone in the Yellow River Delta as the research subjects. Then, the composition and sources of soil dissolved organic matter （DOM） were analyzed based on the UV-vis spectroscopy, three-dimensional excitation emission matrix spectroscopy, and parallel factor analysis （PARAFAC）. Finally, the key factors affecting the characteristics of soil organic carbon and DOM fractions of different plant communities were finally revealed in combination with the physicochemical properties of the soil. The results showed that： ① Comparing different communities, the S. salsa community had the highest ω（SOC） at 7.53 g·kg-1, the T. chinensis community had the highest ω（DOC） at 0.98 g·kg-1, and the P. australis community had significantly higher ω（EOC） and ω（POC） than those of the S. salsa and T. chinensis communities at 1.47 g·kg-1 and 0.65 g·kg-1, respectively. The vertical distribution showed a tendency to decrease with deeper soil layers, except for POC concentration. ② The main components of soil DOM of the P. australis, S. salsa, and T. chinensis communities were humus, protein-like substances, and fulvic acid-like substances, of which exogenous components accounted for 55.80%, 56.41%, and 52.81% in the above communities, respectively. ③ Comparing different communities, the humification degree of the P. australis community was significantly higher than that of the S. salsa and T. chinensi communities, but its aromaticity and proportion of biological sources were significantly lower than those of the T. chinensi community. On the vertical profile of the soil, DOM aromaticity and humification degree gradually increased with the deepening of the soil layer, and the deeper soils were mainly dominated by small molecular weight DOM with a lower proportion of hydrophobic fraction. ④ Redundant analysis showed that N （P<0.01）, NO2--N （P<0.01）, and NH4+-N （P<0.05） were the key factors affecting the changes in soil organic carbon and DOM fractions.

Predicting the thermal decomposition temperature of energetic materials from a simple model.

CONTEXT: The key factor in designing heat-resistant energetic materials is their thermal sensitivity. Further research and prediction of thermal sensitivity remains a great challenge for us. This study is based on first-principles calculations and establishes a theoretical model, which comprehensively considers band gap, density of states, and Young's modulus to obtain a empirical parameter Ψ. A quantitative relationship was established between the new parameter and the thermal decomposition temperature. The value of Ψ is calculated for 10 energetic materials and is found to have a strong correlation with the experimental thermal decomposition temperature. This further proves the reliability of our model. Specifically, the larger the value of Ψ, the higher the thermal decomposition temperature, and the more stable the energetic material will be. Therefore, to some extent, we can use the new parameter Ψ calculated by the model to predict thermal sensitivity. METHODS: Based on first-principles, this paper used the Cambridge Serial Total Energy Package (CASTEP) module of Materials Studio (MS) for calculations. The Perdew-Burke-Ernzerhof (PBE) functionals in Generalized Gradient Approximation (GGA) method as well as the Grimme dispersion correction was used in this paper.

Dynamic memristor for physical reservoir computing.

Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.

Dahuang Zhechong Pill Alleviates Liver Fibrosis Progression by Regulating p38 MAPK/NF-κ B/TGF-ß1 Pathway.

OBJECTIVE: To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis. METHODS: Liver fibrosis cell model was induced by transforming growth factor-ß (TGF-ß) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-ß (15% normal blank serum + 5 ng/mL TGF-ß), DHZCP (15% DMS + 5 ng/mL TGF-ß), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-ß], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-ß). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-ß1 (p38 MAPK/NF-κ B/TGF-ß1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining. RESULTS: DHZCP improves the viability of cells damaged by TGF-ß and reduces inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-ß (P<0.05 or P<0.01). Compared with the TGF-ß group, NF-κ B p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κ B p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-ß group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01). CONCLUSION: DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κ B/TGF-ß1 pathway.

Identification and bioinformatics analysis of genes associated with pyroptosis in spinal cord injury of rat and mouse.

The mechanism of spinal cord injury (SCI) is highly complex, and an increasing number of studies have indicated the involvement of pyroptosis in the physiological and pathological processes of secondary SCI. However, there is limited bioinformatics research on pyroptosis-related genes (PRGs) in SCI. This study aims to identify and validate differentially expressed PRGs in the GEO database, perform bioinformatics analysis, and construct regulatory networks to explore potential regulatory mechanisms and therapeutic targets for SCI. We obtained high-throughput sequencing datasets of SCI in rats and mice from the GEO database. Differential analysis was conducted using the "limma" package in R to identify differentially expressed genes (DEGs). These genes were then intersected with previously reported PRGs, resulting in a set of PRGs in SCI. GO and KEGG enrichment analyses, as well as correlation analysis, were performed on the PRGs in both rat and mouse models of SCI. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING website to examine the relationships between proteins. Hub genes were identified using Cytoscape software, and the intersection of the top 5 hub genes in rats and mice were selected for subsequent experimentally validated. Furthermore, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory mechanisms. The gene expression profiles of GSE93249, GSE133093, GSE138637, GSE174549, GSE45376, GSE171441_3d and GSE171441_35d were selected in this study. We identified 10 and 12 PRGs in rats and mice datasets respectively. Six common DEGs were identified in the intersection of rats and mice PRGs. Enrichment analysis of these DEGs indicated that GO analysis was mainly focused on inflammation-related factors, while KEGG analysis showed that the most genes were enriched on the NOD-like receptor signaling pathway. We constructed a ceRNA regulatory network that consisted of five important PRGs, as well as 24 miRNAs and 34 lncRNAs. This network revealed potential regulatory mechanisms. Additionally, the three hub genes obtained from the intersection were validated in the rat model, showing high expression of PRGs in SCI. Pyroptosis is involved in secondary SCI and may play a significant role in its pathogenesis. The regulatory mechanisms associated with pyroptosis deserve further in-depth research.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

Metal Doped Unconventional Phase IrNi Nanobranches: Tunable Electrochemical Nitrate Reduction Performance and Pollutants Upcycling.

Electrochemical nitrate reduction (NO3RR) provides a new option to abate nitrate contamination with a low carbon footprint. Restricted by competitive hydrogen evolution, achieving satisfied nitrate reduction performance in neutral media is still a challenge, especially for the regulation of this multielectron multiproton reaction. Herein, facile element doping is adopted to tune the catalytic behavior of IrNi alloy nanobranches with an unconventional hexagonal close-packed (hcp) phase toward NO3RR. In particular, the obtained hcp IrNiCu nanobranches favor the ammonia production and suppress byproduct formation in a neutral electrolyte indicated by in situ differential electrochemical mass spectrometry, with a high Faradaic efficiency (FE) of 85.6% and a large yield rate of 1253 µg cm-2 h-1 at -0.4 and -0.6 V (vs reversible hydrogen electrode (RHE)), respectively. In contrast, the resultant hcp IrNiCo nanobranches promote the formation of nitrite, with a peak FE of 33.1% at -0.1 V (vs RHE). Furthermore, a hybrid electrolysis cell consisting of NO3RR and formaldehyde oxidation is constructed, which are both catalyzed by hcp IrNiCu nanobranches. This electrolyzer exhibits lower overpotential and holds the potential to treat polluted air and wastewater simultaneously, shedding light on green chemical production based on contaminate degradation.

Giant Anisotropic Thermal Expansion Phase Transition of Silver Iodide Anionic Organic-Inorganic Hybrid.

Hybrid metal halide materials with charming phase transition behaviors have attracted considerable attention. In former works, much attention has been focused on the phase transition triggered by the order-disorder or displacement motions of the organic component. However, manipulating the variation of the inorganic component to achieve the phase transition has rarely been reported. Herein, two novel organic-inorganic hybrid materials, [THPM]n[AgX2]n (THPM = 3,4,5,6-tetrahydropyrimidin-1-ium, X = I for 1 and Br for 2) with the [AgX2]nn- anionic chain structure, were synthesized. At 293 K, the [AgX2]nn- chains in 1 were constructed by the tetramer units of Ag atoms, while that in 2 was assembled by the dimer structure. Upon heating to 355 K, owing to the variation of the metallophilic interaction between adjacent Ag atoms, a unique transformation process from tetramer to dimer in [AgI2]nn- chains of 1 can be detected and endow 1 with a giant anisotropic thermal expansion with linear strain of ∼7% and shear strain of ∼20%, which can be used as a mechanical actuator for switching. Alternatively, for 2, no phase transition process can be observed upon the temperature variation. This work provides an effective approach to design phase transition materials triggered by the inorganic part.

Photocatalytic reduction of carbon dioxide by BiTeX (X = Cl, Br, I) under visible-light irradiation.

In this study, a series of BiTeX (X = Cl, Br, I) photocatalysts were successfully synthesized via a simple hydrothermal method. The synthesis process involved dissolving BiX3 and Te powder in toluene to identify the most efficient material for photocatalytic activity. The main objective of this approach is to facilitate the conversion of carbon dioxide into sustainable solar fuels, such as alcohols and hydrocarbons, offering an appealing solution to address environmental concerns and energy crises. The BiTeX photocatalysts demonstrated significant proficiency in converting CO2 into CH4, particularly BiTeCl exhibited a notable photocatalytic conversion rate of up to 0.51 µmolg-1h-1. The optimized BiTeX photocatalysts displayed a gradual and selective transition from CO2 to CH4, ultimately producing valuable hydrocarbons (C2+). Furthermore, owing to their ability to reduce CO2, these photocatalysts show promise as materials for mitigating environmental pollution.

ITFG2, an immune-modulatory protein, targets ATP 5b to maintain mitochondrial function in myocardial infarction.

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.