Summary
An unusually high lipid content and a complex lipid profile are the most distinctive features of the mycobacterial cell envelope. However, our understanding of the regulatory mechanism ...underlying mycobacterial lipid metabolism is limited, and the major regulators responsible for lipid homeostasis remain to be characterized. Here, we identified MmbR as a novel master regulator that is essential for maintaining lipid homeostasis in Mycolicibacterium smegmatis. We found that MmbR controls fatty acid β‐oxidation and modulates biofilm formation in Mycolicibacterium smegmatis. Although MmbR possesses the properties of nucleoid‐associated proteins, it acts as a TetR‐like transcription factor, directly regulating and intensively repressing the expression of a group of core genes involved in fatty acid β‐oxidation. Furthermore, both long‐chain acyl‐Coenzyme A and fatty acids appear to regulate the signal molecules modulated by MmbR. The deletion of mmbR led to a significant reduction in intracellular fatty acid content and a decrease in the relative lipid composition of the biofilm. The lack of mmbR led to morphological changes in the mycobacterial colony, defects in biofilm formation and enhanced sensitivity to anti‐tuberculosis drugs. Our study is the first to establish a link between the transcriptional regulation of fatty acid β‐oxidation genes and lipid homeostasis in mycobacteria.
Induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) has been recommended as the first-line therapy for locoregional nasopharyngeal carcinoma (NPC). Due to the different ...chemotherapeutic drugs used in the IC and CCRT, the results remain controversial.
PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically retrieved to search potentially eligible clinical trials up to Sep 11, 2019. Eligible studies were registered and prospective randomized controlled clinical trials.
From 526 records, nine articles including seven randomized controlled clinical trials were eligible, with a total of 2311 locoregional advanced NPC patients. IC + CCRT had significantly lower risks of death (3-year hazard ratio HR: 0.70, 95% confidence interval CI 0.55-0.89, p = 0.003; 5-year HR: 0.77, 95% CI 0.62-0.94, p = 0.01), disease progression (3-year HR: 0.67, 95% CI 0.55-0.80, p < 0.001; 5-year HR: 0.70, 95% CI 0.58-0.83, p < 0.0001), distant metastasis (3-year HR: 0.58, 95% CI 0.45-0.74, p < 0.0001; 5-year HR: 0.69, 95% CI 0.55-0.87, p = 0.001) and locoregional relapse (3-year HR: 0.69, 95% CI 0.50-0.95, p = 0.02; 5-year HR: 0.66, 95% CI 0.51-0.86, p = 0.002) than CCRT. Compared with CCRT, IC + CCRT showed higher relative risks of grade 3 or more neutropenia, thrombocytopenia, nausea, vomiting and hepatotoxicity throughout the course of treatment, and higher relative risks of grade ≥ 3 thrombocytopenia and vomiting during CCRT.
IC combined with CCRT significantly improved the survival in locoregional advanced NPC patients. Moreover, toxicities were well tolerated during IC and CCRT. Further clinical trials are warranted to confirm the optimal induction chemotherapeutic regimen in the future.
Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system-related diseases, immune responses and viral pathogenicity. However, study on the role of ...exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate the antiviral effect on the exosomes of teleost fish. Exosomes isolated from mandarin fish serum by ultra-centrifugation were internalized by mandarin fish fry cells and were able to inhibit Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigate the underlying mechanisms of exosomes in inhibiting ISKNV infection, the protein composition of serum-derived exosomes was analyzed by mass spectrometry. It was found that myxovirus resistance 1 (Mx1) was incorporated by exosomes. Furthermore, the mandarin fish Mx1 protein was proven to be transferred into the recipient cells though exosomes. Our results showed that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication, which suggested an underlying mechanism of the exosome antivirus in that it incorporates Mx1 protein and delivery into recipient cells. This study provided evidence for the important antiviral role of exosomes in the immune system of teleost fish.
Zinc, an abundant transition metal, serves as a signalling molecule in several biological systems. Zinc transporters are genetically associated with cardiovascular diseases but the function of zinc ...in vascular tone regulation is unknown. We found that elevating cytoplasmic zinc using ionophores relaxed rat and human isolated blood vessels and caused hyperpolarization of smooth muscle membrane. Furthermore, zinc ionophores lowered blood pressure in anaesthetized rats and increased blood flow without affecting heart rate. Conversely, intracellular zinc chelation induced contraction of selected vessels from rats and humans and depolarized vascular smooth muscle membrane potential. We demonstrate three mechanisms for zinc-induced vasorelaxation: (1) activation of transient receptor potential ankyrin 1 to increase calcitonin gene-related peptide signalling from perivascular sensory nerves; (2) enhancement of cyclooxygenase-sensitive vasodilatory prostanoid signalling in the endothelium; and (3) inhibition of voltage-gated calcium channels in the smooth muscle. These data introduce zinc as a new target for vascular therapeutics.
Aims
To examine socially, culturally and politically constructed factors affecting family caregiver practice in dementia care, and to identify possible changes in a country with undeveloped dementia ...services.
Background
In China and many other low‐ and middle‐income countries, social transformations are weakening the family care model, which has an impact on the population with dementia. Exploring the challenges that caregivers face may help the international healthcare community to improve dementia services.
Design
A double hermeneutic approach informed by Giddens' Structuration Theory was used.
Methods
In‐depth semi‐structured interviews with 23 family caregivers of people with dementia were conducted in 2012. The interviews were audiotaped, transcribed and analysed.
Findings
Analyses revealed three consequences of socially constructed factors in dementia care, which constrained caregiver practice. First, caregivers were unable to manage behavioural and psychological symptoms of dementia. Untreated aggressive behaviours caused harm to the person with dementia and endangered the caregiver and the public. Second, the burden on the primary caregiver was evident and caregivers received limited support. Third, there was little coordination between primary and specialist care services for people with dementia. On critical reflection of potential changes that could improve dementia services, caregivers suggested that community nurses have a leading role in coordinating dementia services and supporting caregivers.
Conclusion
Relying on family caregivers to care for people with dementia without the prevision of dementia services by the public healthcare system generates negative health outcomes for both care recipients and caregivers. The nursing workforce should be developed to support dementia services.
The effects of complex boundary conditions on flows are represented by a volume force in the immersed boundary methods. The problem with this representation is that the volume force exhibits ...non-physical oscillations in moving boundary simulations. A smoothing technique for discrete delta functions has been developed in this paper to suppress the non-physical oscillations in the volume forces. We have found that the non-physical oscillations are mainly due to the fact that the derivatives of the regular discrete delta functions do not satisfy certain moment conditions. It has been shown that the smoothed discrete delta functions constructed in this paper have one-order higher derivative than the regular ones. Moreover, not only the smoothed discrete delta functions satisfy the first two discrete moment conditions, but also their derivatives satisfy one-order higher moment condition than the regular ones. The smoothed discrete delta functions are tested by three test cases: a one-dimensional heat equation with a moving singular force, a two-dimensional flow past an oscillating cylinder, and the vortex-induced vibration of a cylinder. The numerical examples in these cases demonstrate that the smoothed discrete delta functions can effectively suppress the non-physical oscillations in the volume forces and improve the accuracy of the immersed boundary method with direct forcing in moving boundary simulations.
Developing reliable and user-friendly electroencephalography (EEG) electrodes remains a challenge for emerging real-world EEG applications. Classic wet electrodes are the gold standard for recording ...EEG; however, they are difficult to implement and make users uncomfortable, thus severely restricting their widespread application in real-life scenarios. An alternative is dry electrodes, which do not require conductive gels or skin preparation. Despite their quick setup and improved user-friendliness, dry electrodes still have some inherent problems (invasive, relatively poor signal quality, or sensitivity to motion artifacts), which limit their practical utilization. In recent years, semi-dry electrodes, which require only a small amount of electrolyte fluid, have been successfully developed, combining the advantages of both wet and dry electrodes while addressing their respective drawbacks. Semi-dry electrodes can collect reliable EEG signals comparable to wet electrodes. Moreover, their setup is as fast and convenient similar to that of dry electrodes. Hence, semi-dry electrodes have shown tremendous application prospects for real-world EEG acquisition. Herein, we systematically summarize the development, evaluation methods, and practical design considerations of semi-dry electrodes. Some feasible suggestions and new ideas for the development of semi-dry electrodes have been presented. This review provides valuable technical support for the development of semi-dry electrodes toward emerging practical applications.
Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have ...limited its clinical application, especially in load‐bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC‐AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr‐micro arch oxidation MAO) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr‐MAO was verified by cell adhesion experiment and cell counting kit‐8 (CCK‐8) test. The in vitro osteogenic‐related tests such as immunofluorescence staining, alkaline phosphatase staining and real‐time polymerase chain reaction (RT‐PCR) demonstrated better osteogenic ability of Sr‐MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro‐CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr‐MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr‐MAO porous titanium could be a promising implant load‐bearing bone defect.
guo j., whittemore r. & he g.‐p. (2011) The relationship between diabetes self‐management and metabolic control in youth with type 1 diabetes: an integrative review. Journal of Advanced ...Nursing67(11), 2294–2310.
Aims. The purpose of this integrative review was to describe the relationship between diabetes self‐management and metabolic control in youth with type 1 diabetes and to explore factors which affect this relationship.
Background. In the past 15 years, research has indicated that youth with type 1 diabetes face considerable self‐management challenges and are at increased risk for poor metabolic control. To enhance the development of behavioural interventions for youth with type 1 diabetes, the relationship between diabetes self‐management and metabolic control needs to be more clearly elucidated.
Data Sources. Research studies that examined the relationship between diabetes self‐management and metabolic control in youth with type 1 diabetes were included (n = 18). The electronic databases searched included OVID, MEDLINE (1996 to present), SCOPUS (1996 to January 2010) and PubMed (1996 to January 2010).
Review Method. An integrative literature review was carried out using Whittemore’s modified framework for data collection, analysis and synthesis.
Results. A positive relationship between diabetes self‐management and metabolic control in youth with type 1 diabetes was supported in longitudinal studies and in studies where the mean age was >13 years. Factors influencing this relationship are identified. Measurement of self‐management was quite variable.
Conclusion. Interventions targeting self‐management in youth with type 1 diabetes are indicated, particularly in families of diverse race and ethnicity globally. Further evaluation of the measures of self‐management and more longitudinal research are also indicated.
Microarc oxidation (MAO) is a method about surface treatment that can provide nanoporous pits and thick oxide layers. A kind of porous metal-entangled titanium (Ti) wire material was treated with MAO ...process, resulting in a homogeneous rough TiO2 layer, which helped facilitate MG-63 cell growth, cell viability, early cell differentiation, and cell mineralization in vitro. In addition, the MAO-treated Ti surfaces could promote the proliferation of MG-63 cells without sacrificing differentiation in vitro, which would benefit de novo bone formation around MAO-treated titanium at the early stage. The transcription levels of the extracellular matrix genes of osterix (OSX), collagen type I (Col I), bone sialoprotein (BSP), alkaline phosphatase (ALP), osteocalcin (OC) and osteopontin (OPN) and their protein expression levels were measured, suggesting that the cocultured cells with MAO titanium maintained the osteoblastic phenotype and that the MAO-treated titanium surface greatly stimulated osteoblast cell proliferation and differentiation compared to the untreated titanium. In conclusion, MAO technique can improve the surface of titanium and can contribute to the osseointegration process.
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