Summary
The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated ...vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg‐EGTA)‐treated human serum. After incubation of serum with supernatants enriched in ANCA‐induced NETs, levels of complement components in supernatants were measured by enzyme‐linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b‐9 on NETs incubated with heat‐inactivated normal human serum (Hi‐NHS) or EGTA‐treated Hi‐NHS (Mg‐EGTA‐Hi‐NHS) were significantly less than that on NETs incubated with NHS or EGTA‐treated NHS (Mg‐EGTA‐NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b‐9 concentration decreased from 800·42 ± 244·81 ng/ml, 7·68 ± 1·50 ng/ml, 382·15 ± 159·75 ng/ml in the supernatants enriched in ANCA induced NETs to 479·07 ± 156·2 ng/ml, 4·86 ± 1·26 ng/ml, 212·65 ± 44·40 ng/ml in the supernatants of DNase I‐degraded NETs (P < 0·001, P = 0·008, P < 0·001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV.
Aims: Microglia are involved in neurodegeneration, are prime targets for anti‐inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography ...imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. Methods: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti‐TSPO antibodies. Results: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO‐positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. Conclusions: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti‐inflammatory pharmacological target.
Aims
The study aimed to investigate the inactivation efficacy and mechanisms of plasma activated water (PAW) on selected bacteria in planktonic state.
Methods and Results
Plasma activated water was ...generated using an atmospheric cold plasma jet at 15, 22 and 30 kV for 5 min. Escherichia coli, Listeria innocua, Staphylococcus aureus, Aeromonas hydrophila, Pseudomonas fluorescens and Shewanella putrefaciens were selected as the representative bacterial species. Each bacterial suspension was inoculated into PAW immediately after generation, and the viable counts at different exposure times of 0·5, 1, 3, 5 and 24 h during 4°C storage were measured to determine the inactivation efficacy. Scanning electron microscopy images of the bacteria were conducted to examine the structural changes. Physicochemical properties of PAW, including pH, conductivity, oxidation reduction potential (ORP), and reactive species of H2O2, NO2− and NO3− were measured. The results demonstrated that inactivation efficacy was in positive correlation with voltage and exposure time. Gram‐negative bacteria were more susceptible to PAW than Gram‐positive bacteria. Morphology damage was observed for all the bacterial species. PAW was significantly acidified, conductivity and ORP were significantly increased, and reactive species were detectable after 48 h.
Conclusions
This study offered a better understanding of the inactivation mechanisms of PAW, and the inactivation efficacy can be affected by voltage, exposure time and bacterial species.
Significance and Impact of the Study
This study demonstrated the potential usage of PAW as an alternative disinfectant.
Electroweak W± and Z bosons are powerful probes of the initial stage of the heavy-ion collisions. The measurements of their production is important to disentangle the effects of initial stage from ...the effects of the presence of the quark–gluon plasma (QGP). The production of W± and Z bosons was measured with the ALICE experiment in p–Pb and Pb–Pb collisions exploiting the Z → μ+μ−, W+ → μ+ + νμ and W−→μ−+ν‾μ decay channels. The results and the comparison with theoretical predictions are reported in these proceedings.
The COVID-19 outbreak has raised numerous challenges for mental health service system in China. The pandemic has many affects on clinical, research and teaching, due to the strict quarantine in ...china. Fight the COVID-19 became the most important thing in work. We outlined major mental health needs during COVID-19 outbreak from the exiting studies and challenges for mental health professionals, and how to manage these challenges in China. To reduce the risk of negative psychological outcomes associated with the COVID-19 pandemic, the Central Health Authority of China and different national academic societies have integrated mental health crisis interventions into the general deployment of disease prevention and treatment. The NHCC developed a mental health triage strategy to provide four levels of psychological crisis interventions. More than 20 specific guidelines and expert consensus for mental health services for the COVID-19 outbreak were disseminated by the end of February 2020 to provide timely guidance for frontline health care professionals. External mental health expert teams in other provinces were also established to provide emergency mental health services in Hubei province, China. In addition, widespread adoption of online public education, psychological counseling, and hotline services have been set up for those in need. Although the COVID-19 pandemic has been under control in China, we should take a proactive lead to share its protocol of emergency mental health services with other countries affected by the COVID-19 pandemic. Also international cooperation is urgely needed to control the COVID-19 pandemic worldwide. Large-scale epidemiological surveys should be conducted to examine the prevalence of mental health problems associated with the COVID-19 pandemic to inform the development of appropriate mental health services in future.
Disclosure
No significant relationships.
Summary
This meta-analysis synthesized current evidence from 24 clinical trials to evaluate the impact of different resistance training modes on postmenopausal bone loss. Exercise interventions were ...categorized into two training modes, namely resistance-alone versus combined resistance training protocols. The combined resistance training protocols were defined as the combination of resistance training and high-impact or weight-bearing exercise. The results suggested that the combined resistance training protocols were effective in improving bone mineral density (BMD) at the femoral neck and lumbar spine.
Introduction
The current meta-analysis aimed to examine the effects of combined resistance and resistance-alone training protocols on the preservation of femoral neck and lumbar spine BMD in postmenopausal women.
Methods
An electronic database search was conducted in PubMed, EMBASE, SPORTDiscus, Web of Science, and ProQuest up to March 1, 2014 for the influence of resistance exercise on BMD in postmenopausal women. The study quality was evaluated. The effect sizes were estimated in terms of the standardized mean difference (SMD). A subgroup analysis was conducted by exercise categories.
Results
Twenty-four studies were included in the overall analysis of skeletal response to resistance exercise. The between-study heterogeneity was evident for the hip (
I
2
= 46.5 %) and spine (
I
2
= 62.3 %). The overall analysis suggested that resistance training significantly increased femoral neck BMD (SMD = 0.303, 95 % confidence interval (95 % CI) = 0.127–0.479,
p
= 0.001) and lumbar spine BMD (SMD = 0.311, 95 % CI = 0.115–0.507,
p
= 0.002) in postmenopausal women. However, subgroup analysis indicated that combined resistance training programs significantly affected both the hip BMD (SMD = 0.411, 95 % CI = 0.176–0.645,
p
= 0.001) and spine BMD (SMD = 0.431, 95 % CI = 0.159–0.702,
p
= 0.002), whereas resistance-alone protocols only produced nonsignificant positive effects both on the femoral neck and lumbar spine BMD.
Conclusions
Combined resistance exercise protocols appear effective in preserving femoral neck and lumbar spine BMD in postmenopausal women, whereas resistance-alone protocols only produced a nonsignificant positive effect.
Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological ...relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters.
A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available. Seven complement components (C1q, MBL, Bb, C4d, C3a, C5a, soluble C5b-9) were measured by enzyme-linked immunosorbent assay (Elisa), and any associations between their levels and clinicopathological parameters were then investigated.
In DN patients, plasma levels of C1q, MBL, Bb, C4d, C3a, C5a and sC5b-9 were significantly higher than in diabetes patients without renal involvement, as were also urinary levels except for C1q, which showed no significant differences between the two groups. Also, urinary levels of C3a and C5a were significantly correlated with serum creatinine, urinary protein and estimated glomerular filtration rate, whereas urinary sC5b-9 was significantly correlated with the latter two (and not serum creatinine). In addition, urinary levels of MBL, Bb and C4d were significantly correlated with urinary protein, while C3a, C4d and Bb significantly correlated with the classification of glomerular lesions in DN.
In DN patients, the complement system is activated and, of the three possible complement pathways, activation of the lectin and alternative pathways is associated with renal damage.
The optimization of engineered metabolic pathways requires careful control over the levels and timing of metabolic enzyme expression. Optogenetic tools are ideal for achieving such precise control, ...as light can be applied and removed instantly without complex media changes. Here we show that light-controlled transcription can be used to enhance the biosynthesis of valuable products in engineered Saccharomyces cerevisiae. We introduce new optogenetic circuits to shift cells from a light-induced growth phase to a darkness-induced production phase, which allows us to control fermentation with only light. Furthermore, optogenetic control of engineered pathways enables a new mode of bioreactor operation using periodic light pulses to tune enzyme expression during the production phase of fermentation to increase yields. Using these advances, we control the mitochondrial isobutanol pathway to produce up to 8.49 ± 0.31 g l
of isobutanol and 2.38 ± 0.06 g l
of 2-methyl-1-butanol micro-aerobically from glucose. These results make a compelling case for the application of optogenetics to metabolic engineering for the production of valuable products.
Redox-sensitive trace metals and their isotopes have emerged as important tools that are used to reconstruct the redox-evolution of the ocean-atmosphere system. However, reliability of such ...reconstructions ultimately depends on a solid understanding of the proxies in the present-day oceanic system and their archival potential in sediments. This study compares isotope fractionation of molybdenum (Mo) and uranium (U) during their removal from seawater and deposition into sediments by investigating sites at various depths of the presently two largest restricted anoxic oceanic basins: The Black Sea and the Cariaco Basin. In support of previous investigations, our data indicate that Mo scavenging and isotope fractionation are mainly controlled by water column sulfide levels. In contrast to Mo, U reduction and immobilization appears to occur mainly at the sediment-water interface and within the uppermost few cm of the sediment pile in both basins. In the Black Sea, decreasing δ238U of surface sediments with increasing water depth correlate with trends for water column δ238U, implying constant U isotope fractionation between water and sediment. However, increasing U concentrations and δ238U within the uppermost few cm of the sediment pile of both basins indicate additional U reduction with depth.
Despite the different mechanisms for Mo and U removal and associated isotope fractionations, a similar inverse correlation between δ98Mo and δ238U is observed for sediments of both basins, which translates in a positive correlation of Mo and U isotope fractionation between the sediments and open seawater. The correlation of δ98Mo and δ238U indicates a similar response of isotope fractionation to the efficiency of Mo and U removal that is mainly controlled by sulfate reduction rates. High dissolved sulfide concentrations and sulfate reduction rates are responsible for very effective Mo and U removal and corresponding minor Mo and U isotope fractionation relative to seawater. Further, high dissolved sulfide concentrations also correlate positively with deep water renewal times, resulting in an isotopically fractionated water column with low δ238U (and somewhat higher δ98Mo) in restricted basins with sluggish ventilations, such as the Black Sea. Both mechanisms result in negatively correlated δ98Mo and δ238U with high δ98Mo and low δ238U in sediments under strong euxinic conditions. The particularly strong correlation observed for Cariaco Basin sediments may indicate that its water column was variably stratified in the past.
The observed δ98Mo and δ238U correlation of both basins can be reproduced in a simple coupled water column and sediment reactive transport model. Different slopes in δ98Mo and δ238U trends can be linked to varying degree of basin restriction, sulfate reduction rates, and isotope compositions of the respective water columns. The offset towards lower δ98Mo (and δ238U), observed for Cariaco Basin sediments compared to those from the Black Sea, may be the result of inefficient Mo reduction with high Mo isotope fractionation or isotopically light Mo from a particulate Fe-Mn oxide shuttle. The results of this study will help to interpret sedimentary Mo and U isotope values, while showing that coupling of δ98Mo and δ238U in sedimentary archives may be useful for paleo-reconstruction work.
The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All ...patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.
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