Role and mechanism of NCAPD3 in promoting malignant behaviors in gastric cancer.

Background: Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 (NCAPD3) plays a crucial role in the occurrence of many diseases. However, its role in GC remains unexplored. Materials and Methods: The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze NCAPD3 expression in GC. NCAPD3 was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively. The biological functions of NCAPD3 were investigated in vitro and in vivo. Gene microarray, Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms. Results: NCAPD3 was highly expressed in GC and was associated with a poor prognosis. NCAPD3 upregulation significantly promoted the malignant biological behaviors of gastric cancer cell, while NCAPD3 inhibition exerted a opposite effect. NCAPD3 loss can directly inhibit CCND1 and ESR1 expression to downregulate the expression of downstream targets CDK6 and IRS1 and inhibit the proliferation of gastric cancer cells. Moreover, NCAPD3 loss activates IRF7 and DDIT3 to regulate apoptosis in gastric cancer cells. Conclusion: Our study revealed that NCAPD3 silencing attenuates malignant phenotypes of GC and that it is a potential target for GC treatment.

Optically synchronized unidirectional optical amplifier-based coherent optical fiber links.

We report on the realization of a unidirectional transmission-based bidirectional erbium-doped fiber amplifier (UTB-EDFA) for the coherent optical fiber links. By applying an optical phase-locked loop (OPLL) between the two unidirectional EDFA (Ui-EDFA) paths, the annoying uncorrelated phase noise between the two paths can be largely suppressed. Promisingly, we can independently optimize the gains of the UTB-EDFAs for bidirectional transmissions, resulting in higher net gain acquired compared with the conventional single-path bidirectional EDFA (SPBA)-based ones. We demonstrate that the fractional frequency instability of the UTB-EDFA-based scheme can be decreased by 26.3% over the most asymmetrical 100 km two-way optical frequency comparison (TWC) system compared with the SPBA-based ones and, more importantly, can acquire higher net gain for unevenly distributed sub-links over ultra-long fiber links, such as 1000 km, by independently optimizing the gains. This technique paves the way for the applications of large-scale fiber networks.

Advances and prospects in microbial production of biotin.

Biotin, serving as a coenzyme in carboxylation reactions, is a vital nutrient crucial for the natural growth, development, and overall well-being of both humans and animals. Consequently, biotin is widely utilized in various industries, including feed, food, and pharmaceuticals. Despite its potential advantages, the chemical synthesis of biotin for commercial production encounters environmental and safety challenges. The burgeoning field of synthetic biology now allows for the creation of microbial cell factories producing bio-based products, offering a cost-effective alternative to chemical synthesis for biotin production. This review outlines the pathway and regulatory mechanism involved in biotin biosynthesis. Then, the strategies to enhance biotin production through both traditional chemical mutagenesis and advanced metabolic engineering are discussed. Finally, the article explores the limitations and future prospects of microbial biotin production. This comprehensive review not only discusses strategies for biotin enhancement but also provides in-depth insights into systematic metabolic engineering approaches aimed at boosting biotin production.

SIRT3 protects endometrial receptivity in patients with polycystic ovary syndrome.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls (P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS (P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS: Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.

Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies.

Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib. We investigated the underlying mechanisms using a synthetic Notch reporter system enabling the sorting of cancer cells that directly interact with stromal cells. We identified mucins and bulky glycoprotein synthesis as top-up-regulated genes and pathways by comparing the gene expression and chromatin profiles of stroma-contact and no-contact cancer cells before and after neratinib treatment. Glycoprotein gene signatures were also enriched in human brain metastases compared to primary tumors. We confirmed increased glycocalyx surrounding cocultures by immunofluorescence and showed that mucinase treatment increased sensitivity to neratinib by enabling a more efficient inhibition of EGFR/HER2 signaling in cancer cells. Overexpression of truncated MUC1 lacking the intracellular domain as a model of increased glycocalyx-induced resistance to neratinib both in cell culture and in experimental brain metastases in immunodeficient mice. Our results highlight the importance of glycoproteins as a resistance mechanism to HER2-targeting therapies in breast cancer brain metastases.

Iridium(III) complexes conjugated with naproxen exhibit potent anti-tumor activities by inducing mitochondrial damage, modulating inflammation, and enhancing immunity.

A series of Ir(III)-naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4'-CH2ONPX)](PF6) (Ir-NPX-1-3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1-3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1-3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1-3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) -NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.

Endocytosis blocks the vesicular secretion of exosome marker proteins.

Exosomes are secreted vesicles of ~30 to 150 nm diameter that play important roles in human health and disease. To better understand how cells release these vesicles, we examined the biogenesis of the most highly enriched human exosome marker proteins, the exosomal tetraspanins CD81, CD9, and CD63. We show here that endocytosis inhibits their vesicular secretion and, in the case of CD9 and CD81, triggers their destruction. Furthermore, we show that syntenin, a previously described exosome biogenesis factor, drives the vesicular secretion of CD63 by blocking CD63 endocytosis and that other endocytosis inhibitors also induce the plasma membrane accumulation and vesicular secretion of CD63. Finally, we show that CD63 is an expression-dependent inhibitor of endocytosis that triggers the vesicular secretion of lysosomal proteins and the clathrin adaptor AP-2 mu2. These results suggest that the vesicular secretion of exosome marker proteins in exosome-sized vesicles occurs primarily by an endocytosis-independent pathway.

Black Phosphorus Nanosheets Protect Neurons by Degrading Aggregative α-syn and Clearing ROS in Parkinson's Disease.

Although evidence indicates that the abnormal accumulation of α-synuclein (α-syn) in dopamine neurons of the substantia nigra is the main pathological feature of Parkinson's disease (PD), no compounds that have both α-syn antiaggregation and α-syn degradation functions have been successful in treating the disease in the clinic. Here, it is shown that black phosphorus nanosheets (BPNSs) interact directly with α-syn fibrils to trigger their disaggregation for PD treatment. Moreover, BPNSs have a specific affinity for α-syn through van der Waals forces. And BPNSs are found to activate autophagy to maintain α-syn homeostasis, improve mitochondrial dysfunction, reduce reactive oxygen species levels, and rescue neuronal death and synaptic loss in PC12 cells. It is also observed that BPNSs penetrate the blood-brain barrier and protect against dopamine neuron loss, alleviating behavioral disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model and hA53T α-syn transgenic mice. Together, the study reveals that BPNSs have the potential as a novel integrated nanomedicine for clinical diagnosis and treatment of neurological diseases.

Antiviral and anti-inflammatory activities of chemical constituents from twigs of Mosla chinensis Maxim.

Seven undescribed compounds, including three flavones (1-3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27-29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC50 = 20.47 µM) compared to the positive control oseltamivir (IC50 = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC50 values of 22.78, 20.47, 27.66, and 30.14 µM, respectively.

Obstetrical and neonatal outcomes after vitrified-warmed blastocyst transfer in day 1 rescue intracytoplasmic sperm injection cycles: a retrospective cohort study.

BACKGROUND: Fertilization failure often occurs in conventional IVF cycles, and day 1 rescue ICSI is frequently recommended. In this study, the effect of rescue ICSI on obstetrical and neonatal outcomes after a single blastocyst transfer in vitrified-warmed cycles is evaluated. METHODS: This cohort study was a retrospective analysis of 703 vitrified-warmed single blastocyst transfers and 219 singletons in the r-ICSI group compared with 11,611 vitrified-warmed single blastocyst transfers in the IVF/ICSI and 4472 singletons in the IVF/ICSI group, respectively, and patients just undergoing their first IVF treatments were included in this study. Pregnancy rate (PR), live birth rate (LBR), and singleton birthweight were the primary outcome measures. Multiple linear regression analysis and logistic regression analysis were performed to evaluate the possible relationship between obstetrical and neonatal outcomes and fertilization method (including IVF, ICSI, and r-ICSI) after adjusting for other potential confounding factors. RESULTS: PR and the LBR were lower in the r-ICSI group compared with the IVF/ ICSI group. Singletons from the r-ICSI group had a higher Z-score and the proportion of large for gestational age (LGA) newborns was greater compared with singletons from the IVF/ICSI group. CONCLUSION: The results of the study indicated that a 31% LBR after r-ICSI is acceptable for vitrified-warmed blastocyst transfer, but the safety of transfer is a concern because of the lower PR and LBR compared with IVF/ICSI. The safety of r-ICSI newborns is also a concern because of the significantly higher birthweight and the proportion of LGA in r-ICSI group newborns compared with the IVF/ICSI group.

M2 macrophages participate in ILC2 activation induced by Helicobacter pylori infection.

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. The host immune response evoked by H. pylori infection is complicated and can influence the development and progression of diseases. We have reported that the Group 2 innate lymphocytes (ILC2) were promoted and took part in building type-2 immunity in H. pylori infection-related gastric diseases. Therefore, in the present study, we aim to clarify how H. pylori infection induces the activation of ILC2. It was found that macrophages were necessary for activating ILC2 in H. pylori infection. Mechanistically, H. pylori infection up-regulated the expression of indoleamine 2,3-dioxygenase (IDO) in macrophages to induce M2 polarization, and the latter secreted the alarmin cytokine Thymic Stromal Lymphopoietin (TSLP) to arouse ILC2.

Knowledge domain and emerging trends in anxiety and depression after myocardial infarction research during 2002-2022: Bibliometric and visualized analysis.

Purpose: This study aimed to analyze developmental trends in anxiety and depression after myocardial infarction (ADMI) research in the past 20 years through bibliometrics analysis and predict future research directions. Methods: ADMI-related publications were retrieved from the Web of Science Core Collection. Bibliometric, VOSviewer, CiteSpace, and Bibliometrix software packages were used for bibliometric analysis and visualization. Results: Overall, 3220 ADMI-related publications were identified. The United States, China, and the Netherlands were the countries with the most publications. Carney RM, De Jonge P, and Blumenthal JA were the most influential researchers. In 2004, Van Melle JP, from the University of Groningen, published in Psychosomatic Medicine the most cited article. "Cardiac rehabilitation" was the primary focus area. "Cardiac rehabilitation," "management," "acute coronary syndrome," and "outcome" were the top four keywords in emerging research hotspots. Notably, the effect of traditional Chinese medicine on ADMI is an area of potential research value. Conclusion: Numerous studies have underscored the significance of cardiac rehabilitation. Present research focuses on managing anxiety and depression post-acute coronary syndrome and enhancing clinical outcomes through cardiac rehabilitation technology. Additionally, the therapeutic potential of traditional Chinese medicine for ADMI is expected to attract increased attention from researchers in the future.

Silica Confinement for Stable and Magnetic Co-Cu Alloy Nanoparticles in Nitrogen-Doped Carbon for Enhanced Hydrogen Evolution.

Ammonia borane (AB) with 19.6 wt % H2 content is widely considered a safe and efficient medium for H2 storage and release. Co-based nanocatalysts present strong contenders for replacing precious metal-based catalysts in AB hydrolysis due to their high activity and cost-effectiveness. However, precisely adjusting the active centers and surface properties of Co-based nanomaterials to enhance their activity, as well as suppressing the migration and loss of metal atoms to improve their stability, presents many challenges. In this study, mesoporous-silica-confined bimetallic Co-Cu nanoparticles embedded in nitrogen-doped carbon (CoxCu1-x@NC@mSiO2) were synthesized using a facile mSiO2-confined thermal pyrolysis strategy. The obtained product, an optimized Co0.8Cu0.2@NC@mSiO2 catalyst, exhibits enhanced performance with a turnover frequency of 240.9 molH2 ⋅ molmetal ⋅ min-1 for AB hydrolysis at 298 K, surpassing most noble-metal-free catalysts. Moreover, Co0.8Cu0.2@NC@mSiO2 demonstrates magnetic recyclability and extraordinary stability, with a negligible decline of only 0.8 % over 30 cycles of use. This enhanced performance was attributed to the synergistic effect between Co and Cu, as well as silica confinement. This work proposes a promising method for constructing noble-metal-free catalysts for AB hydrolysis.

Ursodeoxycholic acid loaded dual-modified graphene oxide nanocomposite alleviates cholestatic liver injury through inhibiting hepatocyte apoptosis.

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.

Large-Scale Integration of the Ion-Reinforced Phytic Acid Layer Stabilizing Magnesium Metal Anode.

Rechargeable magnesium batteries (RMBs) have garnered significant attention for their potential in large-scale energy storage applications. However, the commercial development of RMBs has been severely hampered by the rapid failure of large-sized Mg metal anodes, especially under fast and deep cycling conditions. Herein, a concept proof involving a large-scale ion-reinforced phytic acid (PA) layer (100 cm × 7.5 cm) with an excellent water-oxygen tolerance, high Mg2+ conductivity, and favorable electrochemical stability is proposed to enable rapid and uniform plating/stripping of Mg metal anode. Guided by even distributions of Mg2+ flux and electric field, the as-prepared large-sized PA-Al@Mg electrode (5.8 cm × 4.5 cm) exhibits no perforation and uniform Mg plating/stripping after cycling. Consequently, an ultralong lifespan (2400 h at 3 mA cm-2 with 1 mAh cm-2) and high current tolerance (300 h at 9 mA cm-2 with 1 mAh cm-2) of the symmetric cell using the PA-Al@Mg anode could be achieved. Notably, the PA-Al@Mg//Mo6S8 full cell demonstrates exceptional stability, operating for 8000 cycles at 5 C with a capacity retention of 99.8%, surpassing that of bare Mg (3000 cycles, 74.7%). Moreover, a large-sized PA-Al@Mg anode successfully contributes to the stable pouch cell (200 and 750 cycles at 0.1 and 1 C), further confirming its significant potential for practical utilization. This work provides valuable theoretical insights and technological support for the practical implementation of RMBs.

Functional Characterization of PmDXR, a Critical Rate-Limiting Enzyme, for Turpentine Biosynthesis in Masson Pine (Pinus massoniana Lamb.).

As one of the largest and most diverse classes of specialized metabolites in plants, terpenoids (oprenoid compounds, a type of bio-based material) are widely used in the fields of medicine and light chemical products. They are the most important secondary metabolites in coniferous species and play an important role in the defense system of conifers. Terpene synthesis can be promoted by regulating the expressions of terpene synthase genes, and the terpene biosynthesis pathway has basically been clarified in Pinus massoniana, in which there are multiple rate-limiting enzymes and the rate-limiting steps are difficult to determine, so the terpene synthase gene regulation mechanism has become a hot spot in research. Herein, we amplified a PmDXR gene (GenBank accession no. MK969119.1) of the MEP pathway (methyl-erythritol 4-phosphate) from Pinus massoniana. The DXR enzyme activity and chlorophyll a, chlorophyll b and carotenoid contents of overexpressed Arabidopsis showed positive regulation. The PmDXR gene promoter was a tissue-specific promoter and can respond to ABA, MeJA and GA stresses to drive the expression of the GUS reporter gene in N. benthamiana. The DXR enzyme was identified as a key rate-limiting enzyme in the MEP pathway and an effective target for terpene synthesis regulation in coniferous species, which can further lay the theoretical foundation for the molecularly assisted selection of high-yielding lipid germplasm of P. massoniana, as well as provide help in the pathogenesis of pine wood nematode disease.

Fermentation enrichment, structural characterization and immunostimulatory effects of ß-glucan from Quinoa.

We developed an efficient mixed-strain co-fermentation method to increase the yield of quinoa ß-glucan (Q+). Using a 1:1 mass ratio of highly active dry yeast and Streptococcus thermophilus, solid-to-liquid ratio of 1:12 (g/mL), inoculum size of 3.8 % (mass fraction), fermentation at 32 °C for 27 h, we achieved the highest ß-glucan yield of (11.13 ± 0.80)%, representing remarkable 100.18 % increase in yield compared to quinoa ß-glucan(Q-) extracted using hot water. The structure of Q+ and Q- were confirmed through Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopies. Q+ contained 41.66 % ß-glucan, 3.93 % protein, 2.12 % uronic acid; Q- contained 37.21 % ß-glucan, 11.49 % protein, and 1.73 % uronic acid. The average molecular weight of Q+(75.37 kDa) was lower than that of Q- (94.47 kDa). Both Q+ and Q- promote RAW264.7 cell proliferation without displaying toxicity. They stimulate RAW264.7 cells through the NF-κB and MAPK signaling pathways, primarily inducing NO and pro-inflammatory cytokines by upregulating CD40 expression. Notably, Q+ exhibited stronger immunostimulatory activity compared to Q-. In summary, the fermentation enrichment method yields higher content of quinoa ß-glucan with increased purity and stronger immunostimulatory properties. Further study of its bioimmunological activity and structure-activity relationship may contribute to the development of new immunostimulants.

Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.

Ultrasound­targeted microbubble destruction technology delivering ß­klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post­myocardial infarction.

Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co­receptor ß­klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the KLB gene via ultrasound­targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post­acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post­infarction were determined using ELISA. Sprague­Dawley rats received the 3X UTMD­mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post­infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α­klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post­infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. In vivo, the UTMD technology­mediated delivery of KLB@CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2­related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post­myocardial infarction.