Regulation of YAP Promotor Accessibility in Endothelial Mechanotransduction.

BACKGROUND: Endothelial cells are constantly exposed to mechanical forces in the form of fluid shear stress, extracellular stiffness, and cyclic strain. The mechanoresponsive activity of YAP (Yes-associated protein) and its role in vascular development are well described; however, whether changes to transcription or epigenetic regulation of YAP are involved in these processes remains unanswered. Furthermore, how mechanical forces are transduced to the nucleus to drive transcriptional reprogramming in endothelial cells is poorly understood. The YAP target gene, AmotL2 (angiomotin-like 2), is a junctional mechanotransducer that connects cell-cell junctions to the nuclear membrane via the actin cytoskeleton. METHODS: We applied mechanical manipulations including shear flow, stretching, and substrate stiffness to endothelial cells to investigate the role of mechanical forces in modulating YAP transcription. Using in vitro and in vivo endothelial depletion of AmotL2, we assess nuclear morphology, chromatin organization (using transposase-accessible chromatin sequencing), and whole-mount immunofluorescent staining of the aorta to determine the regulation and functionality of YAP. Finally, we use genetic and chemical inhibition to uncouple the nuclear-cytoskeletal connection to investigate the role of this pathway on YAP transcription. RESULTS: Our results reveal that mechanical forces sensed at cell-cell junctions by the YAP target gene AmotL2 are directly involved in changes in global chromatin accessibility and activity of the histone methyltransferase EZH2, leading to modulation of YAP promotor activity. Functionally, shear stress-induced proliferation of endothelial cells in vivo was reliant on AmotL2 and YAP/TAZ (transcriptional coactivator with PDZ-binding motif) expression. Mechanistically, uncoupling of the nuclear-cytoskeletal connection from junctions and focal adhesions led to altered nuclear morphology, chromatin accessibility, and YAP promotor activity. CONCLUSIONS: Our findings reveal a role for AmotL2 and nuclear-cytoskeletal force transmission in modulating the epigenetic and transcriptional regulation of YAP to maintain a mechano-enforced positive feedback loop of vascular homeostasis. These findings may offer an explanation as to the proinflammatory phenotype that leads to aneurysm formation observed in AmotL2 endothelial deletion models.

Prognostic Implication of Pulmonary Arterial Pressure in Surgical Repair of Predominantly Congenital Mitral Valve Regurgitation-Based Intracardiac Abnormalities.

INTRODUCTION: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities. METHODS: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012-2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP >50 mm Hg at rest or mean PAP >25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed. RESULTS: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453-2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807-3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029-1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019-1.055]), respectively. CONCLUSIONS: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP.

PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription.

Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and its co-factor CTCF. They not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina. Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.

Clinical Features and Skin Microbiome of Tinea Scrotum: An Observational Study of 113 Cases in China.

BACKGROUND: The scrotum is considered as an uncommon site for tinea, hence there is a lack of knowledge about the clinical characteristics, pathogenic agents and the skin microbiome changes of tinea scrotum. OBJECTIVE: We sought to analyze the clinical features, pathogenic agents and skin microbiome of tinea scrotum. METHODS: A two-center prospective observational study was carried out in outpatient dermatology clinics in Zhejiang, China, from September 2017 to September 2019. The diagnosis of tinea scrotum was confirmed by direct microscopy. Clinical and mycological data were collected. The composition of microbial communities of patients with tinea scrotum was analyzed and compared with healthy controls. RESULTS: A total of 113 patients with tinea scrotum were included. Tinea scrotum was either presented with isolated lesions (9/113, 8.0%) or accompanied by tinea of other sites (104/113, 92.0%). Tinea cruris was detected in 101 cases (89.38%). Fungal culture was positive in 63 cases, among which Trichophyton rubrum was grown in 60 cases (95.2%) and Nannizzia gypsea was cultured in 3 cases (4.8%). The skin microbiome in scrotum lesions from 18 patients showed increased abundance of Trichophyton compared with 18 healthy individuals, while Malassezia was decreased. No significant difference in bacterial diversity was found. CONCLUSIONS: Tinea scrotum was often companied by superficial fungal infections of other skin sites, with tinea cruris being the most common condition. Instead of N. gypsea, T. rubrum was the most frequently identified pathogen for tinea scrotum. In general, tinea scrotum exhibited changes in the fungal communities of the skin with increased Trichophyton and decreased Malassezia abundance.

Effect of oat ß-glucan on gel properties and protein conformation of silver carp surimi.

BACKGROUND: Polysaccharides are the most widely used additives to enhance the quality of surimi gels. Oat ß-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. However, it has been rarely reported. Therefore, the effect of OG at different levels on gelling properties, protein conformation, and microstructures of silver carp surimi gels were investigated. RESULTS: An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. Moreover, the incorporation of OG (0-1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α-helix to ß-sheet and ß-turn. Consequently, surimi-OG gels displayed a denser network structure with smaller and more uniform voids. Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity. However, a further increase in the OG concentration (1.0-2.0%) resulted in a looser and more uneven network structure with large and numerous cavities. In addition, the whiteness of composite gels decreased with increasing content of OG. CONCLUSION: The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. © 2023 Society of Chemical Industry.

Mixed-Linker Strategy for the Construction of Metal-Organic Framework Combined with Dyes toward Alcohol Detection.

Herein, a N-rich metal-organic framework (MOF) with four kinds of cages, Zn4(ade)2(TCA)2(H2O) (NENU-1000, Hade = adenine, H3TCA = 4,4',4″-tricarboxytriphenylamine, NENU = Northeast Normal University), was prepared by the mixed-ligand strategy. Cationic dyes can be selectively absorbed by NENU-1000 at proper concentrations, but not neutral and anionic dyes, which perhaps can be assigned to the N-rich neutral framework of NENU-1000. When NENU-1000 was introduced to a relatively lower concentration of cationic dye solutions (e.g., rhodamine B or basic red 2), the colors of these systems faded quickly. Furthermore, the faded solutions can be used for the detection of methanol and other small alcohol molecules with either the naked eye or common UV-vis spectra. The effect of the length of carbon chain, the position of the -OH group, and the number of the hydroxyl group of the alcohols was explored for the color development rate. In addition, the performance of NENU-1000 in iodine sorption and release was also studied.

Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

Residue levels, household processing evolution, and risk assessment of chlorothalonil, SDS-3701, metalaxyl, and dimethomorph in Dendrobium officinale Kimura et Migo.

Dendrobium officinale, a minor crop with medicinal and edible value, is increasingly consumed by people, but the pesticide residues on it have received little attention. In this work, field trials were conducted under good agricultural practice conditions to investigate the residues of chlorothalonil, SDS-3701, metalaxyl, and dimethomorph in D. officinale; then the evolution of these pesticides after household processing was studied. The results indicated that chlorothalonil, SDS-3701, metalaxyl, and dimethomorph were 2.41-30.12, 0.20-1.23, 0.07-0.80, and 0.19-7.90 mg kg-1 , respectively, in stems at recommended preharvest interval (30 days). Washing and soaking removed the pesticides in fresh stems with processing factors 0.41-1.14 and 0.12-1.13, respectively. In the brewing test, the transfer rates of pesticides in dry stems decreased from the first time (4.27-95.40%) to the third time (3.89-15.57%). Intake risk assessments were also conducted, and the risk quotients were no more than 27.02% for all compounds in different samples, which indicated acceptable risks for consumers. As effective risk-reducing home-processing methods, washing, soaking, and multiple brewing were suggested in this work, hoping to help consumers with diet safety.

Rotation characteristics and neo-commissural alignment of transcatheter heart valve in type-0 bicuspid aortic valve.

AIMS: This study sought to characterize the rotation of the transcatheter heart valve (THV) and evaluate the neo-commissures overlap with coronary arteries in type-0 bicuspid aortic valve (BAV). METHODS AND RESULTS: This was a single-center, 10-patient, retrospective observational cohort. Pre-TAVI computed tomography and procedural fluoroscopy were analyzed. Coplanar fluoroscopic views were coregistered to pre-TAVI computed tomography to characterize THV rotation and determine coronary overlap. The incidence of severe coronary artery overlap with one coronary artery was 90%. According to our prediction line, type-0 BAV has predicted a higher incidence of overlap with one coronary artery, but lower incidence with both coronary arteries compared to the tricuspid aortic valve (TAV). The rotational angles in two different phases were 3.8 ± 3.2° versus 11.8 ± 8.0° (p = .01) in patients with mixed cusp fusion. Commissural angles in final and initial deployment were 9.6 ± 6.6 versus 18.1 ± 11.0° (p = .021). Applying hypothetic "commissure-middle view" in 0°, ±5°, and ±10°, the incidence of overlap with one coronary artery are 20%, 40%, and 90% separately. CONCLUSIONS: The THV rotation existed and was activated in the last 1/3 deploying phase. With the observed tendency of "automatic commissural alignment," applying the "commissure-middle" view in type-0 BAV may optimize valve alignment and avoid coronary artery overlap.

Assessment of cardiac tumors by 18F-FDG PET/CT imaging: Histological correlation and clinical outcomes.

BACKGROUND: To evaluate the diagnostic value of 18F-FDG PET/CT in distinguishing benign versus malignant cardiac tumors as well as to assess its prognostic value. METHODS: We analyzed 38 patients with cardiac tumors who underwent 18F-FDG PET/CT and followed for median 8.5 ± 12.5 months. SUVmax and TBRmax (maximum tumor-to-background ratio) by receiver-operating characteristic (ROC) curve analysis were used to obtain threshold for the diagnosis of malignancy as defined by histology (n = 38). Survival was assessed and correlated with the dignity of the lesions and PET parameters. RESULTS: Optimal cut-off values indicating malignancy were as follows: SUVmax = 3.44, with 100% sensitivity and 92.9% specificity, and TBRmax = 1.55, with 95.8% sensitivity and 92.9% specificity. A significant difference of 18F-FDG uptake was observed between primary benign (n = 14, SUVmax = 2.35 ± 1.31, TBRmax = 1.05 ± 0.50) compared to primary malignant cardiac tumors (n = 11, SUVmax = 8.90 ± 4.23, TBRmax = 3.82 ± 1.44) as well as cardiac metastases and lymphoma (n = 13, SUVmax = 14.37 ± 8.05, TBRmax = 6.19 ±  3.38) (all P < .001). Survival rate was significantly lower in patients with malignant as compared to benign cardiac tumors (P < .05). Regression analysis revealed that the lesion dignity determined by the cut-off value of SUVmax was an independent predictor for death in patients with cardiac tumors (P < .05). CONCLUSION: 18F-FDG uptake in cardiac tumors can differentiate between benign and malignant cardiac tumors and predicts survival.

A Dilemma in the Extremely Low-Placed Venus A-Valve in a Cardiogenic Shock Patient.

Transcatheter aortic valve replacement (TAVR) is regarded as an alternative to balloon aortic valvuloplasty in patients with severe aortic valve stenosis in cardiogenic shock. A low implantation of transcatheter heart valve (THV) can result in "supraskirt" paravalvular aortic regurgitation (PAR) and prosthesis-patient mismatch (P-PM), causing a dilemma in such a setting. A 64-year-old man presented to our emergency department with severe aortic stenosis and acute heart failure causing cardiogenic shock. An urgent transfemoral TAVR was performed under general anesthesia in a hybrid room. Predilatation was performed with a 22-mm compliant balloon, and a 26-mm Venus A-Valve (Venus MedTech, Hangzhou, China) was deployed. After valve implantation, the hemodynamic conditions of the patient rapidly deteriorated; therefore, cardiopulmonary resuscitation and extracorporeal circulation support were initiated. Aortography and transthoracic echocardiography (TEE) illustrated an extremely low implantation of THV, with moderate to severe supraskirt PAR and moderate P-PM. After evaluation of the hemodynamic tolerability of PAR, a median sternotomy was done, and surgery was performed. The patient died due to severe sepsis and hyperkalemia 14 days after the procedure. The management of urgent TAVR in cardiogenic shock should be revised and reexamined. A widespread and practical percutaneous technique to manage implant failure of THV is required to avoid surgical bailout.

Gender-specific cardiovascular outcomes in patients undergoing percutaneous coronary intervention in Chinese populations.

BACKGROUND: Data was limited on the rates of in-hospital and 30-days composite outcomes between male and female patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). METHODS: This was a retrospective study and CHD patients undergoing PCI between January and December of 2018 were screened and recruited. Baseline characteristics, in-hospital and 30-days composite outcomes were compared by gender. The factors influencing gender-outcome associations were evaluated. RESULTS: A total of 672 CHD patients undergoing PCI were included into current analysis. Compared to males, females were older (53.8 ± 12.7 years vs 50.6 ± 11.8 years), more likely to be obese (32.9% vs 29.4%) and had higher prevalence of hypertension (46.7% vs 41%). Females were less likely to be smoker (30.3% vs 1.1%), have prior history of CHD (4.4% vs 10.9%), and lower socioeconomic status [SES; full-time employment (64.4% vs 71.9%), education attainment ≥ college (29.6% vs 36.8%) and annual income ≥60,000 RMB (23.7% vs 27.1%)]. Hospitalized stay was longer in females (median 5.2 vs 4.0 days), and females were more likely to experience in-hospital bleeding (3.0% vs 1.2%) and 30-days non-fatal myocardial infarction (5.9% vs 2.9%). In unadjusted model, compared to males, females had a crude odds ratio (OR) of 2.05 (95% confidence interval [CI] 1.68-2.59) for in-hospital composite outcomes and 2.16 (95% CI 1.74-2.63) for 30-days post-PCI composite outcomes. After adjustment for potential covariates, female gender remains independently associated with in-hospital and 30-days post-PCI composite outcomes. OR change was the greatest with adjustment for SES when compared to other covariates. CONCLUSION: Compared to male patients, female patients had a higher risk of in-hospital and 30-days composite outcomes post-PCI treatment, which were mainly attributed to the differences in SES.

Two-Dimensional and Three-Dimensional Transthoracic Echocardiography as Predictive and Prognostic Indicators of All-Cause Mortality in Heart Failure with Reduced Ejection Fraction in Patients with Ischemic Heart Disease.

BACKGROUND This study aimed to compare the predictive role of two-dimensional transthoracic echocardiography (2D-TTE) and three-dimensional transthoracic echocardiography (3D-TTE) on in-hospital all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF) due to ischemic heart disease (IHD). MATERIAL AND METHODS Patients (N-224) with HFrEF due to IHD who had a left ventricular ejection fraction (LVEF) <40% on admission when measured by 2D-TTE and 3D-TTE were studied and divided into survival and mortality groups. Baseline demographic and clinical characteristics were compared. RESULTS Compared with the survival group (n=142), patients who died during hospitalization (n=82) were more commonly older (67.3 vs. 62.6 years), female (48.8% vs. 38.7%), with diabetes mellitus (51.2% vs. 32.4%), chronic kidney disease (48.8% vs. 32.4%), intravenous inotropes (85.4% vs. 76.1%), and intravenous vasodilators (70.7% vs. 61.3%). Regression model analysis for all-cause mortality identified significant associations with age, diabetes mellitus, myocardial infarction (MI), intravenous inotropes, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and LVEF following 2D-TTE. Age, diabetes mellitus, prior MI, the use of intravenous inotropes, NT-proBNP, LVEF, and left ventricular end-diastolic volume (LVEDV) index following 3D-TTE were significantly associated with all-cause mortality. Modeling of 2D-TTE parameters showed that the concordance statistic (C-index) increased significantly after including the LVEF, from 0.72 to 0.77 and from 0.72 to 0.80, respectively. Modeling of 3D-TTE parameters showed that the C-index increased significantly after including the LVEDV index (from 0.80 to 0.76). CONCLUSIONS In patients with HFrEF due to IHD, 3D-TTE was a better predictor than 2D-TTE of in-hospital all-cause mortality.

Dissipation, residues and risk assessment of pyraclostrobin and picoxystrobin in cucumber under field conditions.

BACKGROUND: Pyraclostrobin and picoxystrobin are two representative pesticides of strobilurins used to treat cucumber downy mildew, which have raised issues of food safety and human health. A new formulation containing these two compounds is being prepared for marketing in China. RESULTS: The dissipation and residual levels of pyraclostrobin and picoxystrobin in cucumbers under field conditions were determined simultaneously by a validated method via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dissipation rules were described by first-order kinetics and the half-lives of pyraclostrobin and picoxystrobin were less than 8.2 days and 3.4 days. The highest terminal residue of pyraclostrobin was 0.014 mg kg-1 which was lower than maximum residue limit (MRL) in China (0.5 mg kg-1 ) and of picoxystrobin was 0.029 mg kg-1 , respectively. In the long-term intake risk assessment of pyraclostrobin and picoxystrobin for general population (18-79 years), the chronic risk quotient (RQc ) varied from 5.64% to 21.97%. The assessment of short-term risks included children (1-6 years) and adults (18-79 years) and in which the RQa values were 0.38% and 2.85%. Both results showed the intake risks of cucumber were acceptable. CONCLUSION: Pyraclostrobin and picoxystrobin degraded easily in cucumbers under open field conditions. The long-term and short-term risks caused by final residues of pyraclostrobin and picoxystrobin were insignificant. The recommended pre-harvest interval of 3 days was safe. The article will be helpful in rational use of these pesticides and MRL formulation of picoxystrobin on cucumber. © 2020 Society of Chemical Industry.

Effect of heat treatment duration on the interaction between fish myosin and selected flavor compounds.

BACKGROUND: Interactions between flavor compounds and proteins during food processing are critical to flavor perception of the final product. Here, we investigated the effect of the duration of heat treatment on the interaction between bighead carp myosin and selected flavor compounds including hexanal, heptanal, octanal, nonanal, (E)-2-heptenal, and 1-octen-3-ol. RESULTS: The binding of flavor compounds to native myosin was strong and decreased in the order nonanal > octanal > (E)-2-heptenal > heptanal > hexanal >1-octen-3-ol. The aldehydes, especially trans-2-undecenal, were more conducive to hydrophobic binding to myosin than alcohols. Within the initial 5 min of heating, the surface hydrophobicity and total sulfhydryl exposure increased, while α-helix turned into ß-sheets, ß-turns, and random coils. However, upon further heating, the hydrophobicity and sulfhydryl contents declined, ß-sheets, ß-turns and random coils shifted to α-helix. Throughout the heating process, the particle size increased, and the absolute zeta potential decreased continuously, indicating that thermal aggregation of myosin occurred simultaneously. Changes in binding capacities of flavor compounds to myosin were consistent with changes in hydrophobicity and sulfhydryl contents. CONCLUSION: The initial enhancement of the flavor-binding capacity of myosin was attributed to the unfolding of secondary structures by exposing more hydrophobic bonding sites and hydrogen bonding sites. The rebuilding and aggregating of myosin was enhanced upon prolonged heating, thus favoring hydrophobic protein-protein interactions and weakening the resultant flavor binding capacity of myosin.

Binding of aldehydes to myofibrillar proteins as affected by two-step heat treatments.

BACKGROUND: The present study investigated the effect of two-step heat treatments on the structure of grass carp myofibrillar proteins (MPs) and their binding ability for selected aldehydes (hexanal, heptanal, octanal and nonanal). RESULTS: Within 30 min of the first heating step at 40 °C and 5-10 min of the second heating step at 90 °C, the enhancement of the flavor-binding ability was likely explained by the increases in surface hydrophobicity and total sulfhydryl content due to the unfolding of secondary structures of MPs through exposure of hydrophobic amino acids and sulfhydryl groups. Nevertheless, lengthy heating at 90 °C accelerated the aggregation of unfolded MPs and reduced the hydrophobic bonding sites, thus weakening the hydrophobic interactions and decreasing the resultant binding ability of MPs with aldehydes. CONCLUSION: The binding ability of aldehydes to MPs was found to be strongly influenced by changes in protein structure and surface during the two-step heating process. The results provided insight into improving the flavor characteristics of freshwater fish surimi products. © 2019 Society of Chemical Industry.

Hydrolysis of Amisulbrom in Buffer Solutions and Natural Water Samples: Kinetics and Products Identification.

In this study, the hydrolysis of amisulbrom in buffer solutions and natural water samples were investigated. Effects of pH and temperature were tested in buffer solutions. Amisulbrom was stable in acidic and neutral aqueous solutions at 25°C, while quickly hydrolyzed with a half-life of 4.5 days (25°C) at pH 9.0. The kinetics rate equation was determined as k = 1.0234 × 1010 exp (-61.3760/R·T) (R2 = 0.9642) for hydrolysis of amisulbrom at pH 9.0. The pH, ionic strength, and solubility were important factors influencing the hydrolysis of amisulbrom in natural water samples. Furthermore, three hydrolysis products were separated and identified in buffer solution (pH 9.0) and natural water samples. A tentative transformation mechanism of amisulbrom was proposed to rationalize the formation of HPs (hydrolysis products) based on their structural identification, DFT (density functional theory), and hydrolysis profiles. Toxicity prediction using the quantitative structure-activity relationship model revealed that the HP-I, and HP-II were more toxic than the parent amisulbrom. This investigation was the first to evaluate the behavior of amisulbrom hydrolysis in aquatic systems.

KRT1 gene silencing ameliorates myocardial ischemia-reperfusion injury via the activation of the Notch signaling pathway in mouse models.

Myocardial ischemia and reperfusion injury (MIRI) includes major drawbacks, such as excessive formation of free radicals and also overload of calcium, which lead to cell death, tissue scarring, and remodeling. The current study aims to explore whether KRT1 silencing may ameliorate MIRI via the Notch signaling pathway in mouse models. Myocardial tissues were used for the determination of the positive rate of KRT1 protein expression, apoptosis of myocardial cells, creatine kinase (CK) and lactate dehydrogenase (LDH) expression, expression of related biomarkers as well as myocardial infarction area. The transfected myocardial cells were treated with KRT1-siRNA, Jagged1, and DAPT (inhibitor of Notch-1 signaling pathway). The expression of KRT1, NICD, Hes1, Bcl-2, and Bax protein was detected. The MTT assay was applied for cell proliferation and flow cytometry was used for cell apoptosis. Mice with MIRI had a higher positive rate of KRT1 protein expression, apoptosis of myocardial cells, CK and LDH expression, myocardial infarction area, increased expression of MDA, NO, SDH, IL-1, IL-6, TNF-α, CRP, KRT1, Bax protein, CK, and LDH, and decreased expression of SOD, NICD, Hes1, and Bcl-2. The downregulation of KRT1 led to decreased expression of KRT1 and Bax protein, increased expression of NICD, Hes1, and Bcl-2, decreased cell apoptosis, and improved cell proliferation. The inhibition of the Notch signaling pathway leads to reduced expression of Bax, increased expression of NICD, Hes1, and Bcl 2, and also decreased cell apoptosis and increased cell proliferation. Our data conclude that KRT1 silencing is able to make MIRI better by activating the Notch signaling pathway in mice.

The role of microRNA-1 targeting of MAPK3 in myocardial ischemia-reperfusion injury in rats undergoing sevoflurane preconditioning via the PI3K/Akt pathway.

Recent studies have uncovered the vital roles played by microRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1 (miR-1) has been extensively studied and proven to be detrimental to cardiac myocytes. Hence, the current study aimed to explore whether miR-1 affects myocardial ischemia-reperfusion injury (MIRI) in rats undergoing sevoflurane preconditioning and the underlying mechanism. After successful model establishment, rats with MIRI were transfected with mimics or inhibitors of miR-1, or siRNA against MAPK3, and then were injected with sevoflurane. A luciferase reporter gene assay was conducted to evaluate the targeting relationship between miR-1 and MAPK3. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were employed to evaluate the expressions of miR-1, MAPK3, phosphatidylinositol 3-kinase (PI3K), and Akt. Additionally, the concentration of lactate dehydrogenase (LDH) was determined. Cell apoptosis and viability were assessed using TUNEL and cell counting kit-8 assays, and the ischemic area at risk and infarct size were detected using Evans blue and triphenyltetrazolium chloride staining. MAPK3 was found to be the target gene of miR-1. miR-1 expressed at a high level whereas MAPK3 expressed at a low level in MIRI rats. Overexpressing miR-1 or silencing MAPK3 blocked the PI3K/Akt pathway to increase cell apoptosis, ischemic area at risk, and infarct area but decreased cell viability and increased LDH concentration. In contrast, miR-1 downregulation abrogated the effects induced by miR-1 mimics or siRNA against MAPK3. These findings indicate that inhibition of miR-1 promotes MAPK3 to protect against MIRI in rats undergoing sevoflurane preconditioning through activation of the PI3K/Akt pathway.

The roles of SOCS3 and STAT3 in bacterial infection and inflammatory diseases.

The suppressor of cytokine signalling-3 (SOCS3) is well known as a feedback inhibitor of the Janus kinases-signal transducer and activator of transcription 3 (JAK/STAT3) signalling pathway, which mediates the signal transduction of many cytokines, growth factors and hormones during many cellular processes. The critical role of SOCS3 is manifested by its binding to both the JAK kinase and the cytokine receptor, which can result in the inhibition of STAT3 phosphorylation. STAT3 triggers variety of genes expression in response to cytokine (IL-6 family, IL-10) and growth factor stimulation and thus plays a critical role in many cellular biological processes involved in anti/pro-inflammatory responses, cell growth and cell death. SOCS3 might act directly either by hampering JAK activation or by mediating the ubiquitination and subsequent proteasome degradation of the cytokine/growth factor/hormone receptor. Generally, SOCS3 is a negative regulator for cytokine or hormone signalling. But in some cases, SOCS3 regulates the inflammatory responses positively through inhibiting STAT3. An increasing number of reports showed abnormal expression levels of SOCS3/STAT3 in different myeloid and lymphoid cells as well as in various non-hematopoietic cells, which suggested its involvement in various infection and inflammatory diseases. In this review, we described the role of SOCS3 and STAT3 expression in different cell populations in regulating the outcomes of infection and inflammatory diseases.