Tubulin protein is one of several members of a small family of globular proteins. It offers a potential target for anticancer drug design and development. Combretastatin A-4 (CA-4) is a potent ...anticancer and antiangiogenesis natural substance isolated from Combretum caffrum. Modifications on the CA-4 structure have led to a great number of novel CA-4 derivatives as potent tubulin inhibitors and high cytotoxic anticancer agents is becoming an interesting field, leading to a breakthrough in the treatment of cancer. In this review, the recent developments of novel CA-4 derivatives via the modifications on the A- and B-ring and the double bond as anticancer agents are discussed.
Context. The Kilo-Degree Survey (KiDS) is an ongoing optical wide-field imaging survey with the OmegaCAM camera at the VLT Survey Telescope, specifically designed for measuring weak gravitational ...lensing by galaxies and large-scale structure. When completed it will consist of 1350 square degrees imaged in four filters (ugri). Aims. Here we present the fourth public data release which more than doubles the area of sky covered by data release 3. We also include aperture-matched ZYJHKs photometry from our partner VIKING survey on the VISTA telescope in the photometry catalogue. We illustrate the data quality and describe the catalogue content. Methods. Two dedicated pipelines are used for the production of the optical data. The ASTRO-WISE information system is used for the production of co-added images in the four survey bands, while a separate reduction of the r-band images using the THELI pipeline is used to provide a source catalogue suitable for the core weak lensing science case. All data have been re-reduced for this data release using the latest versions of the pipelines. The VIKING photometry is obtained as forced photometry on the THELI sources, using a re-reduction of the VIKING data that starts from the VISTA pawprints. Modifications to the pipelines with respect to earlier releases are described in detail. The photometry is calibrated to the Gaia DR2 G band using stellar locus regression. Results. In this data release a total of 1006 square-degree survey tiles with stacked ugri images are made available, accompanied by weight maps, masks, and single-band source lists. We also provide a multi-band catalogue based on r-band detections, including homogenized photometry and photometric redshifts, for the whole dataset. Mean limiting magnitudes (5σ in a 2″ aperture) and the tile-to-tile rms scatter are 24.23 ± 0.12, 25.12 ± 0.14, 25.02 ± 0.13, 23.68 ± 0.27 in ugri, respectively, and the mean r-band seeing is 0.″70.
We present redshift distribution estimates of galaxies selected from the fourth data release of the Kilo-Degree Survey over an area of ∼1000 deg
2
(KiDS-1000). These redshift distributions represent ...one of the crucial ingredients for weak gravitational lensing measurements with the KiDS-1000 data. The primary estimate is based on deep spectroscopic reference catalogues that are re-weighted with the help of a self-organising map (SOM) to closely resemble the KiDS-1000 sources, split into five tomographic redshift bins in the photometric redshift range 0.1 <
z
B
≤ 1.2. Sources are selected such that they only occupy that volume of nine-dimensional magnitude-space that is also covered by the reference samples (‘gold’ selection). Residual biases in the mean redshifts determined from this calibration are estimated from mock catalogues to be ≲0.01 for all five bins with uncertainties of ∼0.01. This primary SOM estimate of the KiDS-1000 redshift distributions is complemented with an independent clustering redshift approach. After validation of the clustering-
z
on the same mock catalogues and a careful assessment of systematic errors, we find no significant bias of the SOM redshift distributions with respect to the clustering-
z
measurements. The SOM redshift distributions re-calibrated by the clustering-
z
represent an alternative calibration of the redshift distributions with only slightly larger uncertainties in the mean redshifts of ∼0.01 − 0.02 to be used in KiDS-1000 cosmological weak lensing analyses. As this includes the SOM uncertainty, clustering-
z
are shown to be fully competitive on KiDS-1000 data.
Background: Over the past two decades, China has enjoyed impressive economic development, and her citizens have experienced many remarked changes in their lifestyle. These changes are often ...associated with an increase in obesity and chronic disease. Methods: In this meta-analysis, based on nationally representative data, we studied the current prevalence of obesity and the trends in obesity, mortality and morbidity in China. Results: Between 1992 and 2002, the prevalence of overweight and obesity increased in all gender and age groups and in all geographic areas. Using the World Health Organization body mass index cut points, the combined prevalence of overweight and obesity increased from 14.6 to 21.8%. The Chinese obesity standard shows an increase from 20.0 to 29.9%. The annual increase rate was highest in men aged 18-44 years and women aged 45-59 years (approximately 1.6 and 1.0% points, respectively). In general, male subjects, urban residents, and high-income groups had a greater increase. With the increase in overweight and obesity, obesity-, and diet-related chronic diseases (e.g., hypertension, cardiovascular disease (CVD), and type 2 diabetes) also increased over the past decade and became a more important preventable cause of death. Hypertension increased from 14.4% in 1991 to 18.8% in 2002 in adults; in older adults aged 35-74 years, it increased from 19.7 to 28.6%. Between 1993 and 2003, the prevalence of CVD increased from 31.4 to 50.0%; diabetes increased from 1.9 to 5.6%. During 1990-2003, although total mortality rate (per 100 000) decreased, overall the mortality rate and contribution (as percentages) to total death of obesity-related chronic disease increased, in particular, in rural areas. Mortality rate (per 100 000) of CVD increased from 128 to 145 and its contribution to total death, 27 to 32%, in rural areas; the figures decreased slightly in urban areas. The mortality rate of 'nutrition, endocrinology and metabolism-related disease' (NEMD) increased in both rural and urban areas between 1990 and 2000, 8.0 to 10.6 and 4.9 to 5.3, respectively. The current prevalence of hypertension, dyslipidaemia, metabolic syndrome, and diabetes among Chinese adults is approximately 20, 20, 15, and 3%, respectively. Conclusion: The prevalence of overweight and obesity and obesity-related chronic diseases have increased in China in the past decade. Our findings provide useful information for the projection of future trends and the formulation of national strategies and programmes that can address the challenges of the growing obesity and chronic disease epidemic.
The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. ...However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.
Summary
Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated ...vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti‐lysosomal membrane protein‐2 (LAMP‐2) antibody, may have a pathogenic role in AAV. We have shown previously that anti‐LAMP‐2 antibody‐stimulated NET formation contains autoantigens and anti‐microbial peptides. The current study sought to determine whether LAMP‐2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti‐LAMP‐2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti‐LAMP‐2 antibody‐induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP‐2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti‐LAMP‐2 antibody, and this effect was attenuated by the inhibitors of autophagy 3‐methyladenine (3MA) and 2‐morpholin‐4‐yl‐8‐phenylchromen‐4‐one (LY294002). The anti‐LAMP‐2 antibody‐stimulated NET formation was unaffected by benzyloxycarbonyl‐Val‐ Ala‐Asp (OMe)‐fluoromethylketone (zVAD‐fmk) and necrostatin‐1 (Nec‐1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti‐LAMP‐2 antibody. Our results provide further evidence that autophagy is involved in ANCA‐induced NET formation in human neutrophils.
Silicon nanowire films have been modified with boron and used as sensors to measure glucose in aqueous solution. These sensors have a wide linear range (0–10 mM glucose), high sensitivity (172 nA ...mmol–1), good reproducibility, and long‐term stability. Silicon nanowire films have also been modified with magnesium and shown to perform as sensors for detecting hydrogen peroxide in aqueous solution.
Silicon nanowire films (see Figure) modified with boron are used as sensors to monitor glucose in aqueous solution. The sensors have a wide linear detection range and exhibit high sensitivity. They also show good reproducibility and long‐term stability. Silicon nanowire films have also been modified with magnesium and used to detect hydrogen peroxide in aqueous solution.
Summary
This study aimed to examine the frequency of different subsets of circulating B and T follicular helper (Tfh) cells in patients with new‐onset rheumatoid arthritis (RA) and following standard ...therapies. Twenty‐five RA patients and 15 healthy controls (HC) were recruited for characterizing the frequency of CD27+, immunoglobulin (Ig)D+, CD86+, CD95+, Toll‐like receptor (TLR)‐9+ B cells and inducible T cell co‐stimulator (ICOS) and programmed death 1 (PD‐1)‐positive Tfh cells and the level of serum interleukin (IL)‐21. The potential correlation between the frequency of different subsets of B and Tfh cells and the values of clinical measures in RA patients was analysed. In comparison with HC, significantly higher percentages of circulating IgD+CD27−CD19+ naive B, CD86+CD19+ and CD95+CD19+ activated B, CD3+CD4+CXCR5+, CD3+CD4+CXCR5+ICOS+, CD3+CD4+CXCR5+PD‐1+ and CD3+CD4+CXCR5+ICOS+PD‐1+ Tfh cells but lower IgD+CD27+CD19+ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL‐21 in the RA patients. Furthermore, the percentages of CD95+ B cells were correlated positively with the frequency of PD‐1+ Tfh cells, but negatively with ICOS+ Tfh cells. The percentages of CD86+ B cells and ICOS+ Tfh cells were correlated positively with the values of disease activity score 28 (DAS28). Following the drug therapies for 1 month, the percentages of CD86+ B and PD‐1+ Tfh cells were reduced significantly in the drug‐responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers for evaluating the therapeutic responses of individual patients with RA.
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•Metal-free catalysts with N-P-coupled sites were derived from phenoxycycloposphazene.•Hierarchical porosity exposed more active sites and optimized the transportation of O2.•Obtained ...N, P-GCs exhibited impressive catalytic performance for both ORR and OER.
Hierarchical porous N and P co-doped carbons were facilely synthesized by employing phenoxycycloposphazenes (PCPZs) as multi-source of nitrogen, phosphorus and carbon. The pyrolysis of PCPZs that supported on monodispersed silica spheres produced high-surface graphitized carbons (N,P-GCs) with abundant surface N-P coupling sites. The N,P-GCs were demonstrated as efficient metal-free electro-catalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The pore structures of these carbons for exposing more active sites could be adjusted by importing varisized SiO2 spheres (10–50 nm) as hard templates. Typically, N, P-GC-1000 using 30 nm SiO2 as templates exhibits the ORR half-wave potential of 0.85 V in 0.1 M KOH solution, with a loading density of 0.35 mg cm−2 on the electrodes, which is comparable to commercial Pt/C catalyst (0.1 mg cm−2, 20 wt%, JM). Moreover, the OER over N, P-GC-1000 electrodes (0.65 mg cm−2) could also reach 10 mA cm−2 current density at a lower potential of 1.56 V, close to typical RuO2 electrode (1.59 V, 0.2 mg cm−2, Premetek). This work not only suggested a simple and effective pathway to prepare N-P-doped carbon with N,P-coupled sites, but also provided a very efficient metal-free bifunctional carbon electro-catalyst for ORR and OER.
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