Functional characterization of two novel NKX2-1 frameshift variants that cause pulmonary surfactant dysfunction.

BACKGROUND: We aim to report two unrelated patients with pulmonary surfactant dysfunction (PSD) that carried two novel NKX2-1 frameshift variants, and evaluated the impact of these variants in vitro. METHODS: We enrolled children with PSD and NKX2-1 variants, and collected their clinical information and follow-up data. We constructed wild-type (WT) and variant NKX2-1 plasmids and transfected them into A549 and HEK293T cells. The functional characterization of variants was then evaluated by qRT-PCR, western blot, immunofluorescence, electrophoretic mobility shift assay, and dual-luciferase reporter assay. RESULTS: Two novel heterozygous frameshift variants of NKX2-1, i.e., c.705delC (Gly236Alafs*29) and c.313_316 dup (Asn106Lysfs*304), were identified in children from two unrelated families. We discerned attenuated mRNA and protein expression in the Asn106Lysfs*304 variant, and reduced DNA -binding as well as transcriptional activation capabilities in both variants. While the Asn106Lysfs*304 variant lost its synergistic interactions with PAX8 and TAZ, the Gly236Alafs*29 variant partially retained its residual transcriptional activation capabilities and synergistic interactions with PAX8 and TAZ. CONCLUSIONS: We reported on two children with two novel NKX2-1 frameshift variants. In vitro experiments revealed that the two frameshift variants have common and different mechanisms based on the loss or conservation of domains, which partially explained the phenotypical heterogeneity. IMPACT: Pulmonary surfactant dysfunction is a rare heterogeneous disease that exhibits a great burden on children's quality of life. We reported two novel NKX2-1 frameshift variants carried by two children with different clinical phenotypes, thus broadening our knowledge base of gene variations and phenotypes in NKX2-1. We performed an in vitro study and uncovered different pathogenic mechanisms underlying the actions of two novel variants, and thereby partially explained the mechanisms of phenotypical heterogeneity caused by NKX2-1 variants.

Multi-target field control for matrix gradient coils.

OBJECTIVE: Conventional single-target field control for matrix gradient coils will add control complexity in MRI spatial encoding, such as designing specialized fields and sequences. This complexity can be reduced by multi-target field control, which is realized by optimizing the coil structure according to target fields. METHODS: Based on the principle of multi-target field control, the X, Y and Z gradient fields can be set as target fields, and all coil elements can then be divided into three groups to generate these fields. An improved simulated annealing algorithm is proposed to optimize the coil element distribution of each group to generate the corresponding target field. In the improved simulated annealing process, two swapping modes are presented, and randomly selected with certain probabilities that are set to 0.25, 0.5 and 0.75, respectively. The flexibility of the final designed structure is demonstrated by a spherical harmonic basis up to the full second order with single-target field control. An experimental platform is built to measure the gradient fields generated by the designed structure with multi-target target control. RESULTS: With three probabilities of swapping modes, three similar coil element distributions are optimized, and their maximum magnetic field errors for generating X, Y and Z gradients are all below 5%. The structure selected for the final design is the one with a probability of 0.75, considering the coil performance and structural symmetry. The maximum error for all target fields generated by single-target field control is also below 5%. The experimental results show that the measured gradient fields along the axes have enough strength and high linearity. CONCLUSIONS: With the proposed improved simulated annealing algorithm and swapping modes, multi-target field control for matrix gradient coils is verified and achieved in this study by optimizing the coil element distribution. Moreover, this study provides a solution to simplify the complexity of controlling the matrix gradient coil in spatial encoding.

Fast, high-quality, and unshielded 0.2 T low-field mobile MRI using minimal hardware resources.

OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.

Effects of three different plant-derived polysaccharides on growth performance, immunity, antioxidant function, and cecal microbiota of broilers.

BACKGROUND: This study investigated the effects of dietary plant polysaccharides on growth performance, immune status and intestinal health in broilers. We randomly divided 960 one-day-old Arbor Acres broiler chicks into four groups. The control (CON) group was fed a basal diet, and the remaining groups were fed a basal diet supplemented with 1000 mg kg-1 Ginseng polysaccharide (GPS), Astragalus polysaccharide (APS), or Salvia miltiorrhiza polysaccharide (SMP) for 42 days. RESULTS: Dietary supplementation with SMP significantly increased body weight (BW) at 21 and 42 days of age, average daily gain (ADG) and average daily feed intake (ADFI) during the starter and whole experimental period, decreased the concentrations of interleukin-1 beta (IL-1ß), tumor necrosis factor α (TNF-α) and malondialdehyde (MDA), increased the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) and catalase (CAT) activity in the serum (P < 0.05). GPS, APS, and SMP supplementation increased serum levels of immunoglobulins, activities of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC), and cecal concentrations of acetic acid and propionic acid of broilers (P < 0.05). Furthermore, high-throughput sequencing results showed that the relative abundance of Firmicutes was decreased while the relative abundance of Bacteroidota, Alistipes, and Prevotellaceae_NK3B31_group were increased (P < 0.05) in the GPS, APS, and SMP groups compared with the CON group. CONCLUSION: Dietary GPS, APS, and SMP supplementation could improve growth performance, enhance immune function by increasing serum immunoglobulin and regulating cytokines, improve antioxidant function by increasing serum antioxidant enzyme activity, increase volatile fatty acid levels and improve the microbial composition in the cecum of broilers. Dietary SMP supplementation had the optimal effect in this study. © 2023 Society of Chemical Industry.

Optimization design of a permanent magnet used for a low field (0.2 T) movable MRI system.

OBJECTIVE: To design a lightweight permanent magnet for a lowfield movable head imaging MRI system. MATERIALS AND METHODS: To reduce the weight of the magnet, the pole pieces, anti-eddy current plates, and shimming rings were removed, and the distance between the two vertical yokes was shortened as much as possible. To compensate for the magnetic field deformation caused by the shortened distance between two vertical iron yokes, two side magnetic poles were added to the vertical yokes. The magnetic field distributions in magnetic poles, the iron yoke, and the spherical imaging region were simulated. Phantom and in vivo head imaging were conducted with a lowfield movable MRI prototype scanner equipped with the proposed permanent magnet. RESULTS: A permanent magnet with a center field of 0.19815 T, a homogeneity of 46 ppm over the 20 cm spherical imaging region, and a weight of 654 kg have been achieved. Acceptable images of a phantom and a human brain have been acquired with the prototype MRI scanner. DISCUSSION: The proposed permanent magnet design significantly reduces the magnet's weight compared with the conventional magnet structure and shows promise in promoting the development of lowfield compact MRI systems.

Characteristics of brittle cornea syndrome by multimodal imaging modalities: a case report.

BACKGROUND: A report of a Brittle cornea syndrome (BCS) case with bluish scleral discoloration, keratoglobus, and myopia based on multimodal imaging modalities including in vivo confocal microscopy (IVCM), high-definition optical coherence tomography (HD-OCT) and scheimpflug corneal densitometry analysis. CASE PRESENTATION: A 36-year-old Chinese female patient presented with significant bluish discoloration of the sclera in both eyes, extreme corneal thinning with increased corneal curvature, increased central corneal densitometry, and nystagmus. She also had scoliosis, severe osteoporosis, and thyroid disease. CONCLUSIONS: Timely diagnosis, early detection, and detailed follow-up are essential for BCS. There has been no report of a BCS evaluation performed by IVCM and corneal densitometry methods thus far in the literature. Furthermore, multimodal imaging can offer a more comprehensive view of BCS and contribute to a deeper understanding of the disease. Interestingly, this is a rare case of BCS in an adult with good vision, an intact cornea, and nystagmus.

Analysis of coil element distribution and dimension for matrix gradient coils.

OBJECTIVE: The goal of this work is to analyze the influence of the distributions and dimensions of the coil elements and to present a method for improving the performance of the matrix gradient coil. METHODS: Three typical models (five structures in total) are presented, and a double-layer biplanar matrix gradient coil is used to install coil elements. Two metrics, namely, the role of coil elements and mutual inductance between coil elements, are proposed to assess the performance of coil systems. An optimization approach to design matrix gradient coils is introduced based on analyzing the distributions and dimensions of coil elements. The flexibility of the magnetic field generation of the designed coil structure is demonstrated by generating full third-order spherical harmonic fields and different oblique gradient fields. RESULTS: Matrix gradient coils with suitable distributions are capable of generating target magnetic fields. The role of coil elements quantitatively illustrates that the coil elements have different impacts on generating magnetic fields. Increasing the coil element dimension within a certain range can reduce the mutual inductance between coil elements and improve the performance of the coil system. The designed novel double-layer biplanar matrix gradient coil achieves an acceptable performance in generating different magnetic fields. CONCLUSIONS: The proposed metrics can provide theoretical support for designing matrix gradient coils and evaluating their performance. The role of coil elements contributes to analyzing the distributions of coil elements to decrease the number of coil elements and power amplifiers. The mutual inductance between coil elements can be a reference for designing the dimensions of coil elements.

Analysis on matrix gradient coil modeling.

OBJECTIVE: The current distribution of the matrix gradient coil can be optimized via matrix gradient coil modeling to reduce the Lorentz force on individual coil elements. Two different modeling approaches are adopted, and their respective characteristics are summarized. METHODS: The magnetic field at each coil element is calculated. Then, the Lorentz force, torque, and deformation of the energized coil element in the magnetic field are derived. Two modeling approaches for matrix gradient coil, namely, optimizing coil element current (OCEC) modeling and optimizing coil element Lorentz force (OCEF) modeling, are proposed to reduce the Lorentz force on individual coil elements. The characteristics of different modeling approaches are compared by analyzing the influence of the weighting factor on the performance of the coil system. The current, Lorentz force, torque, and deformation results calculated via different modeling approaches are also compared. RESULTS: Coil element magnetic fields are much weaker than the main magnetic field, and their effect can be ignored. Matrix gradient coil modeling with different regularization terms can help to decrease the current and Lorentz force of coil elements. The performance of the coil system calculated via different modeling approaches is similar when suitable weighting factors are adopted. The two modeling approaches, OCEC and OCEF, can better reduce the maximum current and Lorentz force on individual coil elements compared with the traditional modeling approach. CONCLUSIONS: Different modeling approaches can help to optimize the current distribution of coil elements and satisfy various requirements while maintaining the performance of the coil system.

Short-term effects of two types of goggles on intraocular pressure and anterior eye segment biometrics.

BACKGROUND: To evaluate and compare the changes in intraocular pressure and anterior eye segment biometrics during and after wearing two types of commonly used swimming goggles. METHODS: In a cross-sectional study, a total of 40 healthy adults aged between 18 and 60 years old were selected to wear two kinds of common swimming goggles (ocular socket and orbital goggles). Intraocular pressure and anterior segment biometry were evaluated before wearing, at 2 and 5 min of wearing, and at 5 min after removing the goggles. Intraocular pressure (IOP), corneal front keratometry values (K1, K2, Km), central corneal thickness (CCT), central anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were measured. RESULTS: The IOP at 2 min (21.0 ± 2.2 mmHg) and 5 min (21.2 ± 2.3 mmHg) was significantly higher than before wearing goggles (17.7 ± 2.1 mmHg). The IOP after the goggles were removed and at 5 min after the goggles were removed was 18.4 ± 2.3 mmHg and 17.7 ± 2.1 mmHg, respectively. ACV, ACD, and ACA values all decreased while the googles were worn. After the goggles were removed, these changes gradually returned to baseline values, with no significant difference in the values before and after. CONCLUSION: This study proves that wearing orbital goggles can lead to an acute increase in IOP and a slight decrease in ACV, ACD, and ACA. However, once the goggles are removed, these indicators return to baseline levels, showing that wearing orbital goggles has no significant lasting effect on IOP and anterior segment parameters.

Puerarin reduces impairment of intestinal and adipose immune responses to influenza virus infection in mice.

Influenza is an acute viral respiratory disease that can also cause gastroenteritis-like symptoms, such as abdominal pain, nausea, vomiting, and diarrhea. Immune dysfunction of adipose tissue is involved in the occurrence and prognosis of influenza viral pneumonia. In this study, we analyzed intestinal and adipose immune responses in mice infected with influenza virus and found that the impairment of intestinal and adipose immunity to influenza virus infection could be reversed by treatment with puerarin, a medicinal compound isolated from Pueraria lobata (called "gegen" in Chinese). We found that the lungs, small intestines (duodenum, ileum, jejunum) and large intestines (colon and rectum) of infected mice showed obvious inflammatory lesions, with significantly increased levels of virus, inflammatory cytokines (interleukin [IL]-6, IL-17, and tumor necrosis factor-α), Toll-like receptors 3, 4, and 9, and integrin αvß3 and α4, and a decreased level of secreted IgA compared to the normal control group (NC) (P < 0.05-0.001). Influenza virus infected mesenteric lymph nodes and adipose tissue, and adipokines (leptin, visfatin, "chemerin", and adiponectin) of lung and mesenteric adipose tissue were dysregulated. Puerarin treatment reversed the impairment of the intestinal and adipose immune responses in mice infected with influenza virus. Our findings suggest that influenza virus can infect adipose tissue and lead to intestinal adipose immune dysfunction in normal-weight mice and that the impairment of the intestinal and adipose immune response to influenza virus infection can be reversed by puerarin treatment.

Molecular-Scale Mechanism of Sequential Reaction of Oxalic Acid with SO3: Potential Participator in Atmospheric Aerosol Nucleation.

Recent research has shown the almost barrierless cycloaddition reaction of the carboxylic acid with one SO3 to form products with group of -OSO3H, which can form stable clusters with the nucleation precursors through hydrogen bonds (Mackenzie et al., Science 2015, 349, 58). Oxalic acid (OA), the simplest and prevalent dicarboxylic acid, was selected as an example to clarify the possibility to react with two SO3 sequentially and the nucleation potential of products. The results indicate that OA can sequentially react with two SO3 through low reaction barriers to form the primary product (oxalic sulfuric anhydride (OSA)) and the secondary product (oxalic disulfuric anhydride (ODSA)). Interactions between atmospheric nucleation precursors and OSA, ODSA, or OA are in the order of ODSA > OSA > OA through evaluating the stability of generated clusters by the topological, thermodynamics, and kinetic analysis, which implies generated products could be nucleation stabilizers with nucleation potential positively correlating with the number of -OSO3H. This reaction mechanism contributes to a comprehensive understanding of the reactivity of dicarboxylic acid in the polluted environment as well as the role of products in organosulfur chemistry and, to some extent, help to explain the missing sources of new particle formation.

Antiviral activity of puerarin as potent inhibitor of influenza virus neuraminidase.

Puerarin is a major isofiavone compound isolated from the root of Pueraria lobata. It was reported that puerarin had antioxidant, antiinflammatory, antitumor, cholesterol lowering, liver protective, and neuroprotective properties. However, few studies have explored the antiviral effect of puerarin and its target mechanism related to influenza virus. Here, the antiinfluenza activity of puerarin in vitro and in vivo and its mode of action on the potential inhibition of neuraminidase (NA) were investigated. Puerarin displayed an inhibitory effect on A/FM/1/1947(H1N1) (EC50 = 52.06 µM). An indirect immunofluorescence assay indicated that puerarin blocked the nuclear export of viral NP. The inhibition of NA activity confirmed that puerarin can block the release of newly formed virus particles from infected cells. Puerarin (100 and 200 mg/kg/d) exhibited effective antiviral activity in mice, conferring 50% and 70% protection from death against H1N1, reducing virus titers, and effectively alleviating inflammation in the lungs. The molecular docking results showed that puerarin had a strong binding affinity with NA from H1N1. The results of the molecular dynamics simulation revealed that puerarin had higher stable binding at the 150-loop region of the NA protein. These results demonstrated that puerarin acts as a NA blocker to inhibit influenza A virus both in cellular and animal models. Thus, puerarin has potential utility for the treatment of the influenza virus infection.

Polygalasaponin F treats mice with pneumonia induced by influenza virus.

BACKGROUND: Influenza is an acute viral respiratory illness that causes high morbidity and mortality globally. Therapeutic actions are limited to vaccines and a few anti-viral drugs. Polygala (P.) japonica herba is rich in Polygalasaponin F (PSF, C53H86O23), used for acute bronchitis, pharyngitis, pneumonia, amygdalitis, and respiratory tract infections treatment in China. Hypercytokinemia is often correlated with severe pneumonia caused by several influenza viruses. PSF was reported to have anti-inflammatory effects and its mechanism is associated with the nuclear factor (NF)-κB signaling pathway. The action of PSF to alleviate pulmonary inflammation caused by influenza A virus (IAV) infection requires careful assessment. In the present study, we evaluated the effect and mechanism of PSF on mice with pneumonia caused by influenza H1N1 (A/FM/1/47). METHODS: Mice were infected intranasally with fifteen 50% mouse lethal challenge doses (MLD50) of influenza virus. BALB/c mice were treated with PSF or oseltamivir (oral administration) for 2 h post-infection and received concomitant treatment for 5 days after infection. On day 6 post-infection, 10 mice per group were killed to collect related samples, measure body weight and lung wet weight, and detect the viral load, cytokine, prostaglandins, pathological changes, and cell pathway protein expression in the lungs. In addition, the survival experiments were carried out to investigate the survival of mice. The expression profile of cell pathway proteins was detected and analyzed using a broad pathway antibody array and confirmed the findings from the array by western blotting. RESULTS: Polygalasaponin F and oseltamivir can protect against influenza viral infection in mice. PSF and oseltamivir significantly relieved the signs and symptoms, reduced body weight loss, and improved the survival rate of H1N1-infected mice. Moreover, PSF efficiently decreased the level of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-4, interferon (IFN)-γ, thromboxane A2 (TXA2), and prostaglandin E2 (PGE2) in lung tissues of mice infected with influenza virus (p < 0.05-0.01). Oseltamivir had a similar effect to lung cytokine of PSF, but did not decrease the levels of TXA2 and PGE2. There was a twofold or greater increase in four cell pathway protein, namely NF-κB p65 (2.68-fold), I-kappa-B-alpha (IκBα) (2.56-fold), and MAPK/ERK kinase 1 (MEK1) (7.15-fold) assessed in the array induced by influenza virus. Western blotting showed that the expression of these proteins was significantly decreased in lung after influenza virus challenge in PSF and oseltamivir-treated mice (p < 0.05-0.01). CONCLUSION: Polygalasaponin F appears to be able to augment protection against IAV infection in mice via attenuation of pulmonary inflammatory responses. Its effect on IAV-induced pulmonary inflammation was associated with suppression of Raf/MEK/ERK and NF-κB expressions.

Ultrasound accelerated synthesis of O-alkylated hydroximides under solvent- and metal-free conditions.

A novel, sustainable, environmentally friendly, high substrate scope, efficient, solvent-free and metal catalyst-free method for the cross-dehydrogenative coupling (CDC) reaction between N-hydroxyphthalimide (NHPI) and benzyl/ether compounds is described. This coupling reaction proceeds through ultrasound acceleration. Compared to conventional heating conditions, the use of ultrasound techniques not only improves the reaction efficiency and enhances the reaction rate but also minimizes the side reactions.

TBAI-catalyzed selective synthesis of sulfonamides and ß-aryl sulfonyl enamines: coupling of arenesulfonyl chlorides and sodium sulfinates with tert-amines.

A simple, practical and metal-free method has been developed for the synthesis of sulfonamides and ß-arylsulfonyl enamines via the selective cleavage of C-N and C-H bonds through the iodine-catalyzed oxidation of arenesulfonyl chlorides and sodium sulfinates with tert-amines. The method uses commercially available inexpensive catalysts and oxidants, and has a wide substrate scope and operational simplicity.

[Levels of autoantibodies against AT1-receptor in hypertensive patients with acute coronary syndromes and its role in coronary artery vasoconstriction].

OBJECTIVE: To explore the levels of autoantibodies against AT1-receptor (AT1-AA) in hypertensive patients with acute coronary syndrome (ACS) and observe the in vitro effects of AT1-AA on resting tension of isolated anterior descending artery of vascular ring in male Wistar rats. METHODS: All patients were recruited from June 2007 to August 2008. There were hypertensive patients with ACS (n = 120), those with simple hypertension (n = 253) and those with simple ACS (n = 115). And the outpatients for health examination during the same period were selected as healthy control group (n = 188). The second extracellular loop amino acid sequences of peptides of ATI receptor was synthesized and used as antigen (AT1-Ag) and sialic acid-enzyme-linked immunosorbent assay (SA-ELISA) for detect the serum levels of AT1-AA. Microvascular ring tension technology was used to test the vascular loop resting tension of anterior descending coronary artery from rats induced by a high-fat diet. RESULTS: The positive rates of AT1-AA in patients with simple hypertension (35.2%) and those with simple ACS (30.4%) were significantly higher than those in healthy control group (7.2%, P < 0.01). And the positive rate of AT1-AA in hypertensive patients with ACS (43.3%) was significantly higher than that in those with simple hypertension (35.2%, P < 0.05) and that in healthy control group (7.2%, P < 0.05).Furthermore, AT1-AA increased the vascular loop resting tension of anterior descending coronary artery rings in rats induced by a high-fat diet in a dose-dependant manner. And the vasoconstrictive action of AT1-AA was equal to 46.4% of AngII's action. And such an action was blocked by losartan and antigens. CONCLUSION: The level of AT1-AA increases markedly in hypertensive patients with ACS. And AT1-AA induces vasoconstrictive effects on anterior descending artery rings in rats induced by a high-fat diet.

[Cardiac protective effect of the autoantibody against ß3-adrenoceptor in rats with experimental heart failure].

OBJECTIVE: To explore the effect of the autoantibody against the ß3-adrenoceptor on rats with experimental heart failure. METHOD: The peptide corresponding to the sequence of ß3 adrenoceptor was synthesized to actively immunize the rats, ELISA was used to detect the serum level of autoantibody against the ß3-adrenoceptor (ß3AA). Total IgGs were extracted from the serum containing ß3AA in immunized rats. Aortic banding surgery was used to establish the heart failure model in male Wistar rats and rats were divided into the sham group (n = 8), heart failure group(n = 8),ß3AA-immunized heart failure group (HF+ß3AA, n = 8) and corresponding negative IgG-immunized heart failure group (HF+ IgG, n = 8).In 6 weeks and 8 weeks after aortic banding surgery, the serum levels of NT-pro brain natriuretic peptide (NT-proBNP) were assayed with ELISA assay and cardiac function was assessed by echocardiography. RESULTS: ß3AA was used to immunize rat with heart failure, the serum level of ß3AA was stable at 50 days post immunization. At 8 weeks after aortic banding surgery, heart failure group showed significantly increased LVEDD [(6.92 ± 0.22) mm vs.(5.62 ± 0.19) mm, P < 0.001], LVESD [(4.63 ± 0.23) mm vs.(3.50 ± 0.20) mm, P < 0.01] and IVS [(2.44 ± 0.06) mm vs.(2.28 ± 0.05) mm, P < 0.05], and decreased LVEF[(62.07 ± 3.99)% vs.(79.63 ± 3.02)%, P < 0.01] and LVFS [(31.46 ± 3.22)% vs.(43.65 ± 2.68) %, P < 0.05] compared with the sham group.HF+ß3AA IgG group showed decreased LVEDD [(6.07 ± 0.30) mm vs.(6.92 ± 0.24) mm, P < 0.05] and LVESD [(3.92 ± 0.22) mm vs.(4.68 ± 0.23) mm, P < 0.05], and higher LVEF [(70.29 ± 1.78)% vs.(61.95 ± 3.03)%, P < 0.05] and LVFS [(38.08 ± 2.32)% vs.(30.50 ± 1.82)%, P < 0.05] compared to the HF+ IgG group.In addition, compared with the HF+ IgG group, HF+ß3AA IgG group showed decreased serum levels of NT-proBNP [(196.43 ± 6.56) pg/ml vs.(242.13 ± 7.86) pg/ml, P < 0.01]. CONCLUSION: Our results demonstrate that ß3AA can improve cardiac function and reduce the serum levels of NT-proBNP in rat with heart failure.

Identification and molecular docking of xanthine oxidase and α-glucosidase inhibitors in Opuntia ficus-indica fruit.

Opuntia ficus-indica fruit (OFI) is rich in bioactive compounds, which can promote human health. In this work, the purified OFI extract was prepared from OFI and its bioactivities were investigated. Xanthine oxidase (XOD) and α-glucosidase (α-Glu) inhibitors of the purified OFI extract were screened and identified by bio-affinity ultrafiltration combined with UPLC-QTRAP-MS/MS technology. The inhibitory effect of these inhibitors on enzymes were verified, and the potential mechanism of action and binding sites of inhibitors with enzymes were revealed based on molecular docking. The results showed that the total phenolic content of the purified OFI extract was 355.03 mg GAE/g DW, which had excellent antioxidant activity. Additionally, the extract had a certain inhibitory effect on XOD (IC50 = 199.00 ± 0.14 µg/mL) and α-Glu (IC50 = 159.67 ± 0.01 µg/mL). Seven XOD inhibitors and eight α-Glu inhibitors were identified. Furthermore, XOD and α-Glu inhibition experiments in vitro confirmed that inhibitors such as chlorogenic acid, taxifolin, and naringenin had significant inhibitory effects on XOD and α-Glu. The molecular docking results indicated that inhibitors could bind to the corresponding enzymes and had strong binding force. These findings demonstrate that OFI contains potential substances for the treatment of hyperuricemia and hyperglycemia.