Interplay of Hypoxia-Inducible Factors and Oxygen Therapy in Cardiovascular Medicine

Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have questioned the excessive use of oxygen therapy and have identified specific cardiovascular diseases in which a more conservative approach to oxygen therapy could be beneficial compared with a more liberal approach. In this Review, we provide numerous perspectives on systemic and molecular oxygen homeostasis and the pathophysiological consequences of excessive oxygen use. In addition, we provide an overview of findings from clinical studies on oxygen therapy for myocardial ischaemia, cardiac arrest, heart failure and cardiac surgery. These clinical studies have prompted a shift from liberal oxygen supplementation to a more conservative and vigilant approach to oxygen therapy. Furthermore, we discuss the alternative therapeutic strategies that target oxygen-sensing pathways, including various preconditioning approaches and pharmacological HIF activators, that can be used regardless of the level of oxygen therapy that a patient is already receiving

Preoperative albumin-to-fibrinogen ratio predicts chemotherapy resistance and prognosis in patients with advanced epithelial ovarian cancer

Abstract Background Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery. Methods A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan–Meier method using log-rank test. Results The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan–Meier method by log-rank test (P < 0.001). Conclusions A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery

The Interaction between B87 Vaccine Strain and BC6/85 of Infectious Bursa Disease Virus in SPF Chickens

This study was initiated to determine the interaction between two infectious bursal disease virus (IBDV) strains in the early stages of infection by detection and quantification of IBDV RNA in lymphoid and non-lymphoid tissues. SPF chickens were inoculated with single infection or dual infection by the mild strain B87 followed by the pathogenic strain BC6/85 at 0, 1, 2, and 3 days post-inoculation (dpi) with B87. Real-time RT-PCR assays were developed to examine the viral loads of the tissues collected at various time intervals. The results reveal that B87 could delay the time point of positive detection of the BC6/85 strain in the bursa of Fabricius from 1 dpi to 3 dpi, indicating that B87 interfered with the replication of BC6/85. The interference occurred when BC6/85 was inoculated at 2 dpi and 3 dpi with the B87 strain. Moreover, BC6/85 could affect the proliferation and duration of B87 in SPF chickens. The rates of positive detection for B87 decreased significantly during dual infection. The investigation of the interaction between the two strains is important for the implementation of appropriate control measures

Isogeometric Analysis for Active Control of Piezoelectric Functionally Graded Plates in Thermal Environment

An isogeometric analysis (IGA) method is proposed for investigating the active shape and vibration control of functionally graded plates (FGPs) with surface-bonded piezoelectric materials in a thermal environment. A simple first-order shear deformation theory (S-FSDT) with four variables is used to describe the displacement field of the plates. To ensure the investigation of smart piezoelectric structure in the thermal environment closer to the actual situation, a modified piezoelectric constitutive equation with consideration of the temperature effect of dielectric and piezoelectric strain coefficients is implemented to replace the traditional linear piezoelectric constitutive equation. Meanwhile, the neutral surface is adopted to avoid the stretching-bending coupling. The accuracy and effectiveness of the proposed S-FSDT-based IGA method are verified by comparing with several existing numerical examples. Then, the static bending and open-loop control of the plates under mechanical and thermal loads are further studied. Finally, the active control including static bending control and vibration control of piezoelectric functionally graded plates (PFGPs) is also investigated by using a displacement-velocity feedback control law

Circulating Memory T Follicular Helper Cells in Patients with Neuromyelitis Optica/Neuromyelitis Optica Spectrum Disorders

Objective. This study aimed to examine the potential role of memory T follicular helper (Tfh) cells in patients with neuromyelitis optica/neuromyelitis optica spectrum disorders (NMO/NMOSD). Methods. The percentages of different subsets of circulating memory Tfh cells in 25 NMO/NMOSD patients before and after treatment as well as in 17 healthy controls were examined by flow cytometry. The levels of IL-21 and AQP4 Ab in plasma and CSF were measured by ELISA. Results. The percentages and numbers of circulating memory Tfh cells, ICOS+, CCR7−, CCR7−ICOS+, CCR7+, CCR7+ICOS+ memory Tfh cells, and the levels of IL-21 in plasma and CSF were significantly increased in NMO/NMOSD patients. The percentages of CCR7− and CCR7−ICOS+ memory Tfh cells were positively correlated with ARR, plasma IL-21, and AQP4 Ab levels. The percentages of CCR7+ and CCR7+ICOS+ memory Tfh cells were positively correlated with CSF white blood cell counts, proteins, and IL-21 levels. Treatment with corticosteroids significantly reduced the numbers of CCR7−ICOS+ and CCR7+ICOS+ memory Tfh cells as well as plasma IL-21 levels in patients with partial remission. Conclusions. Our findings indicate that circulating memory Tfh cells may participate in the relapse and development of NMO/NMOSD and may serve as a new therapeutic target

Assessment of M. longissimus fibre types and metabolic enzymes in Bama miniature pigs and Landrace swine

Overt differences exist between Chinese local pigs and exotic pig breeds, especially in muscle growth rate and meat quality. However, the underlying molecular mechanisms remain unclear. This study aimed to assess muscle fibre types and metabolic enzymes in Bama miniature pigs and Landrace swine. Meat quality traits, including intramuscular fat content, and muscle colour, conductivity, and tenderness, were assessed in these pig breeds. Then, muscle fibre types were classified, and mRNA amounts and activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) assessed, in M. longissimus from the two pig breeds, at various ages. Our data showed significantly higher back fat thickness, muscle conductivity, and intramuscular fat content in samples from Bama miniature pigs compared with the values obtained for Landrace pigs (p < .05). In addition, SDH activity was significantly higher, and LDH activity overtly lower in Bama pigs compared with Landrace swine (p < .05). Furthermore, myosin heavy-chain (MyHC) II A, II B, and II X mRNA levels in Bama miniature pigs at 180 were significantly higher than values obtained for Landrace pigs of the same age. Although MyHC I gene expression levels were similar in Bama miniature and Landrace pigs at 180 days of age, significantly higher amounts were obtained in 300 day old Bama miniature pigs compared with 180 day old Landrace pigs (p < .05). Collectively, these preliminary findings indicated that skeletal muscles from Bama miniature pigs may contain more oxidative fibres compared with those from Landrace pigs, which might explain the meat quality differences between the two pig breeds

Identification, Genetic Analysis, and Pathogenicity of Classical Swine H1N1 and Human-Swine Reassortant H1N1 Influenza Viruses from Pigs in China

Swine influenza virus causes a substantial disease burden to swine populations worldwide and poses an imminent threat to the swine industry and humans. Given its importance, we characterized two swine influenza viruses isolated from Shandong, China. The homology and phylogenetic analyses showed that all eight gene segments of A/swine/Shandong/AV1522/2011(H1N1) were closely related to A/Maryland/12/1991(H1N1) circulating in North America. The HA, NA, M, and NS genes of the isolate were also confirmed to have a high homology to A/swine/Hubei/02/2008(H1N1) which appeared in China in 2008, and the virus was clustered into the classical swine lineage. The gene segments of A/swine/Shandong/AV1523/2011(H1N1) were highly homologous to the early human H1N1 and H2N2 influenza viruses, except for the HA gene, and the virus was a reassortant H1N1 virus containing genes from the classical swine (HA) and human (NA, PB2, PB1, PA, NP, M, and NS) lineages. Both the viruses could cause lethal infection and replicate efficiently in the lungs, brains, spleens, and kidneys of mice. Histopathological examinations showed that AV1522 and AV1523 viruses caused a spectrum of marked pneumonia and meningoencephalitis according to the duration of infection, demonstrating a progression of respiratory disease and neurological disease over the course of infection that ultimately resulted in lethality for the infected mice. The changes in the pathogenicity of swine influenza viruses to mammals, accompanied with the continuous reassortment and evolution of the viruses, highlights the importance of ongoing epidemiological investigation

Cascade Molecule–Particle–Molecule Self-Assemblies for Fabricating Narrowly Size-Distributed Polymeric Superparticles with a Bicontinuous Nanostructure

Broader developments of nanoscience and nanotechnology require complexly but regularly structured nanoparticles whose fabrications in turn pose a great challenge to nanoscience and nanotechnology. In this communication, we report a new and robust method with a clear mechanism for fabricating narrowly size-distributed superparticles with a bicontinuous inner structure. The processes for the fabrication include: molecular self-assembly of a triblock copolymer in its selective solvent into the core–shell–corona micelles, the self-limited aggregation of the micelles (particles) into narrowly size-distributed superparticles constructed by the integrated micelles, and the final molecular self-assembly confined within the superparticles into cylinders that are crowded and interconnected to form the bicontinuous nanostructure; the molecular self-assembly into the micelles, the self-limited aggregation of the particles (i.e., the micelles), and the further molecular self-assembly within the superparticles occurred in a cascade manner