Cardiac abnormalities after induction of endoplasmic reticulum stress are associated with mitochondrial dysfunction and connexin43 expression

The endoplasmic reticulum (ER) is responsible for protein synthesis and calcium storage. ER stress, reflected by protein unfolding and calcium handling abnormalities, has been studied as a pathogenic factor in cardiovascular diseases. The aim of this study is to examine the effects of ER stress on mechanical and electrophysiological functions in the heart and explore the underlying molecular mechanisms. A total of 30 rats were randomly divided into control, ER stress inducer (tunicamycin[TN]) and ER stress inhibitor (tunicamycin+4-phenylbutyric acid [4-PBA]) groups. ER stress induction led to significantly systolic and diastolic dysfunction as reflected by maximal increasing/decreasing rate of left intraventricular pressure (±dp/dt), left ventricular peaksystolic pressure(LVSP) and LV end-diastolic pressure(LVEDP). Epicardial mapping performed in vivo revealed reduced conduction velocity and increased conduction heterogeneity associated with the development of spontaneous ventricular tachycardia. Masson’s trichrome staining revealed marked fibrosis in the myocardial interstitial and sub-pericardial regions, and thickened epicardium. Western blot analysis revealed increased pro-fibrotic factor transforming growth factor-β1 (TGF-β1), decreased mitochondrial biogenesis protein peroxlsome proliferator-activated receptor-γ coactlvator-1α （PGC-1a）, and decreased mitochondrial fusion protein mitofusin-2 (MFN2). These changes were associated with mitochondria dysfunction and connexin 43(CX43)translocation to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA. Our study shows that ER stress induction can produce cardiac electrical and mechanism dysfunction as well as structural remodelling. Mitochondrial function alterations are contributed by CX43 transposition to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin‐induced myocardial injury

Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate-buffered saline, doxorubicin, and doxorubicin with resveratrol). Results Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α-smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin‐induced myocardial injury

Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose‐dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin‐induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin‐induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods: Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate‐buffered saline, doxorubicin, and doxorubicin with resveratrol). Results: Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α‐smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion: Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin‐induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function

Ceramides and metabolic profiles of patients with acute coronary disease: a cross-sectional study

Metabolic Syndrome (MS) is a rapidly growing medical problem worldwide and is characterized by a cluster of age-related metabolic risk factors. The presence of MS increases the likelihood of developing atherosclerosis and significantly raises the morbidity/mortality rate of acute coronary syndrome (ACS) patients. Early detection of MS is crucial, and biomarkers, particularly blood-based, play a vital role in this process. This cross-sectional study focused on the investigation of certain plasma ceramides (Cer14:0, Cer16:0, Cer18:0, Cer20:0, Cer22:0, and Cer24:1) as potential blood biomarkers for MS due to their previously documented dysregulated function in MS patients. A total of 695 ACS patients were enrolled, with 286 diagnosed with MS (ACS-MS) and 409 without MS (ACS-nonMS) serving as the control group. Plasma ceramide concentrations were measured by LC-MS/MS assay and analyzed through various statistical methods. The results revealed that Cer18:0, Cer20:0, Cer22:0, and Cer24:1 were significantly correlated with the presence of MS risk factors. Upon further examination, Cer18:0 emerged as a promising biomarker for early MS detection and risk stratification, as its plasma concentration showed a significant sensitivity to minor changes in MS risk status in participants. This cross-sectional observational study was a secondary analysis of a multicenter prospective observational cohort study (Chinese Clinical Trial Registry, https://www.who.int/clinical-trials-registry-platform/network/primary-registries/chinese-clinical-trial-registry-(chictr), ChiCTR-2200056697), conducted from April 2021 to August 2022

Fingerprinting of Nitroaromatic Explosives Realized by Aphen-functionalized Titanium Dioxide

Developing sensing materials for military explosives and improvised explosive precursors is of great significance to maintaining homeland security. 5-Nitro-1,10-phenanthroline (Aphen)-modified TiO2 nanospheres are prepared though coordination interactions, which broaden the absorption band edge of TiO2 and shift it to the visible region. A sensor array based on an individual TiO2/Aphen sensor is constructed by regulating the excitation wavelength (365 nm, 450 nm, 550 nm). TiO2/Aphen shows significant response to nitroaromatic explosives since the Aphen capped on the surface of TiO2 can chemically recognize and absorb nitroaromatic explosives by the formation of the corresponding Meisenheimer complex. The photocatalytic mechanism is proved to be the primary sensing mechanism after anchoring nitroaromatic explosives to TiO2. The fingerprint patterns obtained by combining kinetics and thermodynamics validated that the single TiO2/Aphen sensor can identify at least six nitroaromatic explosives and improvised explosives within 8 s and the biggest response reaches 80%. Furthermore, the TiO2/Aphen may allow the contactless detection of various explosives, which is of great significance to maintaining homeland security

Investigation of internal damage evolution in gneiss considering water softening

Abstract In soft rock tunnels, there are often large deformations during construction, especially when the groundwater seepage and softens the surrounding rock. For achieving the purpose of studying the softening effect of water immersion on strength and stability of surrounding rock, 15 rock samples were selected for physical and mechanical tests under 5 conditions: natural state and free immersion for 1, 3, 6, and 9 months, and nuclear magnetic resonance technology(NMR) was also adopted to test the internal pore structure of specimens with different immersion durations, thus the micro structure features of the gneiss, such as the NMR relaxation time T2 spectrum distribution, porosity, and pore volume ratio of different pore sizes under water softening were then obtained. The NMR results shows that the longer the free immersion duration of the rock sample, the greater the porosity; at the same time, the number of micropores in the rock gradually decreases under the interaction of water and rock, and the mesopores increase slightly first and then decrease all the time. The number of macropores is gradually increasing. When the immersion duration is 6 months, the number of macropores begins to increase significantly, and the mechanical properties of the specimens begin to drop significantly. By 9 months, the proportion of macropores in the rock has reached 57.6%. The results showed that the number growth of macropores is the root cause of the macroscopic failure of rock sample. The study results have significance for on-site construction in water-rich areas

Investigation on the Properties of Gneiss under Different Ground Stresses

Initial geostress has great influence on the properties of gneiss. The physical and mechanical properties of gneiss vary considerably due to different initial geostresses, which exert a huge effect on the stability of underground engineering. In order to explore the influence of initial ground stress on the properties of gneiss. Changes in the physical properties (e.g., P-wave velocity and volumetric weight), mechanical properties (e.g., compressive strength, elastic modulus, and residual strength) and failure mode of gneiss are analyzed by conducting physical and mechanical tests on gneiss in different ground stress areas. The results show that high geostress can improve the pre-peak mechanical properties of gneiss, and weaken its post-peak mechanical properties. When the initial geostress is greater, the pre-peak mechanical properties are better, and the post-peak mechanical properties are worse. The failure mode of gneiss under high ground stress is primarily brittle failure. When the initial ground stress is greater, brittleness is stronger. According to the research results of this paper, it can provide the basis for the optimization and improvement of underground engineering support in gneiss strata with high geostress. The research results have important reference value and guiding significance for underground engineering construction in high geostress gneiss areas

Sediment nitrite-dependent methane-oxidizing microorganisms temporally and spatially shift in the Dongjiang River

Nitrite-dependent anaerobic methane oxidation (n-damo) process can play an important role in the methane mitigation in the environment. However, the distribution of n-damo organisms in freshwater sediment ecosystem and the associated environmental factors remain essentially unclear. The present study investigated the temporal and spatial dynamics of sediment n-damo community in the freshwater Dongjiang River using quantitative PCR assay and clone library analysis targeting n-damo pmoA gene. Sediment samples were collected at nine locations along the Dongjiang River in May and August in 2015. The remarkable temporal and spatial changes of sediment n-damo community abundance, richness, diversity, and structure occurred in the Dongjiang River and its tributaries. The n-damo pmoA gene in sediments of the Dongjiang River and its tributaries varied from 9.07 x 10(4) to 3.02 x 10(6) copies per gram dry sediment. Compared to the stem of the Dongjiang River, tributaries had relatively higher sediment n-damo community size. Sediment n-damo community abundance was higher in August than in May, while an opposite trend was observed for n-damo community richness and diversity. Sediment n-damo community structure showed a great difference between in May and August. Sediment nitrite nitrogen content was positively correlated to n-damo community abundance, but negatively to richness and diversity. Ammonia nitrogen content showed a positive correlation to n-damo community abundance, while n-damo community diversity was negatively correlated to the ratio of total organic carbon to total nitrogen (C/N). In addition, nitrite nitrogen as well as C/N might influence n-damo community structure.National Natural Science Foundation of China [41001323, 41571444]SCI(E)PubMedARTICLE1401-41010

Hyperspectral Features of Oil-Polluted Sea Ice and the Response to the Contamination Area Fraction

Researchers have studied oil spills in open waters using remote sensors, but few have focused on extracting reflectance features of oil pollution on sea ice. An experiment was conducted on natural sea ice in Bohai Bay, China, to obtain the spectral reflectance of oil-contaminated sea ice. The spectral absorption index (SAI), spectral peak height (SPH), and wavelet detail coefficient (DWT d5) were calculated using stepwise multiple linear regression. The reflectances of some false targets were measured and analysed. The simulated false targets were sediment, iron ore fines, coal dust, and the melt pool. The measured reflectances were resampled using five common sensors (GF-2, Landsat8-OLI, Sentinel3-OLCI, MODIS, and AVIRIS). Some significant spectral features could discriminate between oil-polluted and clean sea ice. The indices correlated well with the oil area fractions. All of the adjusted R2 values exceeded 0.9. The SPH model1, based on spectral features at 507–670 and 1627–1746 nm, displayed the best fitting. The resampled data indicated that these multi-spectral and hyper-spectral sensors could be used to detect crude oil on the sea ice if the effect of noise and spatial resolution are neglected. The spectral features and their identified changes may provide reference on sensor design and band selection