HSP70 alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial dysfunction-initiated NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes.

Background: Sepsis-induced cardiomyopathy (SIC) is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality. Heat shock proteins (HSPs) have been implicated in suppressing septic inflammation. The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction, exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention. Methods: Mice with cecal ligation plus perforation (CLP) and lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes were used as models of SIC. The mouse survival rate, gross profile, cardiac function, pathological changes and mitochondrial function were observed by photography, echocardiography, hematoxylin-eosin staining and transmission electron microscopy. In addition, cell proliferation and the levels of cardiac troponin I (cTnI), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by Cell Counting Kit-8, crystal violet staining and enzyme-linked immunosorbent assay. Moreover, mitochondrial membrane potential was assessed by immunofluorescence staining, and dynamin-related protein 1 and pyroptosis-related molecules [nucleotide-binding domain, leucine-rich-repeat containing family pyrin domain-containing 3 (NLRP3), caspase-1, gasdermin-D (GSDMD), gasdermin-D N-terminal (GSDMD-N)] were measured by western blotting, immunoprecipitation and immunoblotting. Finally, hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism. Results: Models of SIC were successfully established, as reduced consciousness and activity with liparotrichia in CLP mice were observed, and the survival rate and cardiac ejection fraction (EF) were decreased; conversely, the levels of cTnI, TNF-α and IL-1ß and myocardial tissue damage were increased in CLP mice. In addition, LPS stimulation resulted in a reduction in cell viability, mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro. HSP70 treatment improved myocardial tissue damage, survival rate and cardiac dysfunction caused by CLP. Additionally, HSP70 intervention reversed LPS-induced mitochondrial destabilization, inhibited activation of the NLRP3 inflammasome, caspase-1, GSDMD and GSDMD-N, and decreased pyroptosis. Finally, knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity, and exogenous HSP70 significantly rescued these changes. It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules. Conclusions: Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC. Interestingly, HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the activation of NLRP3 inflammasome-mediated pyroptosis, and such a result may provide approaches for novel therapies for SIC.

A novel red phosphor Ca2 YNbO6 :Eu3+ for WLEDs.

Due to the advantages of good physicochemical properties, thermal stability, and optical properties, double perovskite compounds have received extensive attention. On this basis, a new type of red phosphor, Ca2 YNbO6 :xEu3+ , was synthesized using a high-temperature solid-phase method. Its phase purity, morphology, elemental composition, absorption spectrum, photoluminescence, thermal stability, and Commission Internationale de l'éclairage (CIE) chromaticity coordinates were thoroughly investigated. The results display that there is no impurity phase in the samples and the convergence factor Rwp = 14.2%; the microscopic particles are uniform and full, and the distribution of each element is uniform. The energy band gap ΔE is between 3.71 eV and 3.65 eV. The luminescence intensity is the best when the doped Eu3+ concentration x reaches 0.4, and emits 612 nm red light (5 D0 →7 F2 ) under 465 nm excitation, and the concentration quenching is attributed to a d-d interaction. The luminescence intensity at 425 K was still 75% of the room temperature luminescence intensity, which indicates that the thermal stability is extremely superior. The CIE chromaticity coordinates (0.6534, 0.3455) of the Ca2YNbO6:0.4Eu3+ phosphors are very close to National Television Standards Committee (0.670, 0.330), and the samples have low correlated colour temperature (2656 K) and high colour purity (99.90%). All findings suggest that Ca2 YNbO6 :Eu3+ can serve as a substitute for red phosphor in WLEDs.

Partially cystic thyroid nodules on ultrasound: The associated factors for malignancy.

OBJECTIVES: To identify the associated factors for malignancy in partially cystic thyroid nodules (PCTNs) on ultrasound (US). MATERIALS AND METHODS: This is a retrospective study. 338 PCTNs confirmed by surgery was included in this study. The US features of the nodules were reviewed and their significance in differential diagnosis was analyzed. RESULTS: In the 338 PCTNs, 50 were malignant and 288 were benign. Univariate analyses revealed that a taller-than-wide shape and spiculated or microlobulated margin were significantly associated with malignancy while the spongy form, an ovoid to round shape and smooth margin were significantly associated with benign nature. In terms of the internal solid portion of the nodule, eccentric configuration, non-smooth margin, hypoechogenicity, and microcalcification were more frequently demonstrated in malignant nodules than in benign ones. In the multivariate logistic regression analysis, a taller than wide shape (OR: 13.357; 95% CIs: 3.457-28.797) was revealed to be the strongest independent predictor for malignancy, followed by microcalcification (OR: 11.578; 95% CIs: 3.142-29.563), spiculated or microlobulated margin (OR: 6.331; 95% CIs: 1.425-9.457), eccentric configuration (OR: 5.456; 95% CIs: 1.358-8.774), non-smooth rim of the internal solid portion (OR: 4.897; 95% CIs: 0.754-7.021), and hypoechogenicity of the internal solid portion (OR: 4.651; 95% CIs: 0.712-8.245). CONCLUSIONS: Understanding the ultrasound characteristics of malignant PCTNs is important to make a precise diagnosis of thyroid nodules.

Nondiagnostic cytological results on ultrasound-guided fine needle aspiration: Does the thyroid nodule depth matter?

OBJECTIVE: To evaluate whether thyroid nodule depth and other ultrasound features can predict nondiagnostic cytological results on ultrasound-guided fine needle aspiration. MATERIAL AND METHODS: This retrospective study included 412 thyroid nodules that underwent ultrasound-guided fine needle aspiration from 2014 to 2015. The nodules were classified as nondiagnostic and diagnostic by the cytopathological results. Clinical information of the patients (ie., age, sex) and ultrasound features (ie., size, depth, calcification, cystic content, vascularity) of the nodules were recorded and compared between the nondiagnostic group and diagnostic group. RESULTS: Age and sex were not significantly different between the nondiagnostic group and diagnostic group (P > 0.05). Nodule depth >15 mm (OR, 7.128; P < 0.001), peripheral rim calcification (OR, 5.725; P = 0.01) and cystic content >50% (OR, 2.995; P = 0.018) were factors for the nondiagnostic ultrasound-guided fine needle aspiration cytopathological results. Macrocalcification in the nodule sized 5-10 mm was associated with the nondiagnostic results (P = 0.04). Nodule size and vascularity were not associated with the nondiagnostic results (P > 0.05). CONCLUSIONS: Nodule depth >15 mm, peripheral rim calcification and cystic content >50% were three independent predictors of the nondiagnostic cytopathological results. Macrocalcification in the nodule sized 5-10 mm was also associated with the nondiagnostic results.

NADPH oxidase 1 and its derived reactive oxygen species mediated tissue injury and repair.

Reactive oxygen species are mostly viewed to cause oxidative damage to various cells and induce organ dysfunction after ischemia-reperfusion injury. However, they are also considered as crucial molecules for cellular signal transduction in biology. NADPH oxidase, whose only function is reactive oxygen species production, has been extensively investigated in many cell types especially phagocytes. The deficiency of NADPH oxidase extends the process of inflammation and delays tissue repair, which causes chronic granulomatous disease in patients. NADPH oxidase 1, one member of the NADPH oxidase family, is not only constitutively expressed in a variety of tissues, but also induced to increase expression in both mRNA and protein levels under many circumstances. NADPH oxidase 1 and its derived reactive oxygen species are suggested to be able to regulate inflammation reaction, cell proliferation and migration, and extracellular matrix synthesis, which contribute to the processes of tissue injury and repair.