Nonsense variants in KIDINS220/ARMS were identified as the main cause of spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, a rare disease with birth defects in ...brachycephaly, neurological disorder, and obesity. The cause of neural cell dysfunction by KIDINS220/ARMS were extensively studied while the cause of obesity in SINO syndrome remains elusive. Here, we identified KIDINS220/ARMS as an adipocyte differentiation-regulating gene. A Chinese family, mother and her two sons, all showed severe symptoms of SINO syndrome. G-banding karyotyping, chromosome microarray analysis, and whole exome sequencing revealed a novel amber mutation, c.3934G>T (p. E1312X), which was close to the C-terminal region of KIDINS220/ARMS and resulted in the premature of the protein. Both the mRNA and protein levels of KIDINS220/ARMS gradually decreased during adipocyte differentiation. Knockdown of KINDINS220/ARMS could prompt adipocyte differentiation and lipid accumulation while overexpression of KIDINS220/ARMS decrease the rate of matured adipocytes. Furthermore, we demonstrated that KIDINS220/ARMS inhibits adipocyte maturation through sustained extracellular signal-regulated kinase signaling. In conclusion, this is the first report about a vertical heredity of severe dominant pathogenic mutation of KIDINS220/ARMS, suggested that KIDINS220/ARMS played a negative role in adipocyte maturation, explained the cause of obesity in SINO syndrome and could highlight the importance of adipocyte differentiation in neuron functions.
Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low‐density lipoprotein receptor ...(LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis‐related PF (SSc‐PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low‐density lipoprotein (LDL) increased in SSc‐PF and IPF patients. The disrupted LDL–LDLR metabolism was also observed in four mouse PF models. Upon bleomycin (BLM) treatment, Ldlr‐deficient (Ldlr−/−) mice exhibited remarkably higher LDL levels, abundant apoptosis, increased fibroblast‐like endothelial and ATII cells and significantly earlier and more severe fibrotic response compared to wild‐type mice. In vitro experiments revealed that apoptosis and TGF‐β1 production were induced by LDL, while fibroblast‐like cell accumulation and ET‐1 expression were induced by LDLR knockdown. Treatment of fibroblasts with LDL or culture medium derived from LDL‐pretreated endothelial or epithelial cells led to obvious fibrotic responses in vitro. Similar results were observed after LDLR knockdown operation. These results suggest that disturbed LDL–LDLR metabolism contributes in various ways to the malfunction of endothelial and epithelial cells, and fibroblasts during pulmonary fibrogenesis. In addition, pharmacological restoration of LDLR levels by using a combination of atorvastatin and alirocumab inhibited BLM‐induced LDL elevation, apoptosis, fibroblast‐like cell accumulation and mitigated PF in mice. Therefore, LDL–LDLR may serve as an important mediator in PF, and LDLR enhancing strategies may have beneficial effects on PF.
Pulmonary fibrosis (PF) is a devastating lung disorder of unknown etiology. We show that disrupted LDL‐LDLR metabolism in human and mouse PF, and then investigated their contributions and underlying mechanisms for PF progression from endothelial/epithelial injury to eventual fibrosis. Pharmacological restoration of LDLR expression can abolish LDL redundancy and prevent PF features.
•UV exposure and high temperature dealing can enhance the cross-linking and solidity of DR1/SU-8.•Resistivity of polymer claddings can indicate the origin of EO response distinction of core–cladding ...couples.•NOA73 as cladding suggests low optical loss, strong and stable EO response for DR1/SU-8 waveguide.•The series of characterizations in the paper can be applied to find out favorable passive cladding for EO polymer waveguide.
The physic-chemical compatibility of passive cladding and poled Dispersed Red 1 (DR1) doped ultraviolet (UV) curable polymer SU-8 was investigated. The multilayer films consisting of DR1/SU-8 core and Norland Optical Adhensive 73 (NOA73), SU-8, polydimethylsiloxane (PDMS), or polymethylmethacrylate (PMMA) upper-cladding were fabricated on the silicon substrate, respectively. The interface morphologies were characterized through scan electronic microscope. Parallel plate electric field poling was carried out to align the polarity of chromophores in SU-8. The core–cladding interface with no chemical erosion or delamination was obtained by adopting an excess UV exposure and higher temperature dealing when NOA73 was used as the upper-cladding. The root mean square roughness of the upper-cladding surface was measured by atomic force microscope to verify the poling process. The electro-optic (EO) signal response amplitude of these multilayer films was used to characterize the polarizability alignment of DR1 chromophores by means of Teng–Man method after poling. Resistivity of claddings was measured at the glass transition temperature of DR1/SU-8 to explain the EO response difference. The configuration of NOA73/(DR1/SU-8) exhibited the best EO performance and time relaxation in amplitude within 550h by prolonging the cooling time in poling process. A channel waveguide was fabricated to study the poling-induced optical loss. The results show that the selection of passive cladding with favorable electrical and chemical property is essential to establish optical nonlinearity in the dye–polymer system.
Studies have shown that the application of arbuscular mycorrhizal (AM) fungi or exogenous melatonin (MT) can alleviate drought stress and improve plant growth, but the additive effects of both ...treatments on plants grown under drought stress are largely unknown. In this study, we conducted a pot experiment to investigate the effects of AM inoculation (
Funneliformis mosseae
BGC XJ01) and/or MT application on tobacco (
Nicotiana tabacum
L. cv. Yuyan No. 6) seedling growth, photosynthetic and chlorophyll fluorescence parameters, antioxidant enzymatic activity, osmotic adjustment substance accumulation, and nutrient uptake under three water conditions (75–80%, 50–55%, and 30–35% of the maximum moisture retention capacity). The results show that applying either the AM inoculant or MT alone significantly increased tobacco seedling growth and decreased the negative effects of drought stress. Furthermore, AM inoculation alone promoted root function (root biomass, root/shoot ratio, root system architecture), facilitated the capture and conversion of solar energy (photosynthetic rate,
Φ
PSII
), and increased nutrient uptake more effectively than MT. In contrast, exogenous MT application alone was more effective at increasing peroxidase and catalase activity and decreasing H
2
O
2
and MDA accumulation, which in turn enhanced the adaptation of seedlings to drought stress by improving their antioxidant capacity and reducing oxidative damage. Nevertheless, applying exogenous MT significantly enhanced the AM colonization rate under AM inoculation conditions but had no obvious effect on AM colonization under noninoculated conditions. The combined application of AM and MT had an additive effect and produced the largest increases in tobacco seedling growth, photosynthetic ability, antioxidant enzymatic activity, and N, P, and K uptake and the largest decreases in H
2
O
2
and MDA contents of all the treatments. The results suggest that AM inoculation in combination with exogenous MT application may render plants more productive and more tolerant of drought stress.
In order to provide some useful lessons to basin water resources management practice, this paper summarized the successful experience of the two modes of basin water resources management in the ...United States; one is the mode of the bureau of river basin water resources management represented in Tennessee, and the other is the mode of the committee of river basin water resources management represented in Delaware. The result shows that the improvement in legislation and management and coordination capacity and the increase in multi-stakeholder involvement is the key issue in the water resources management
Abstract We consider the problem of large‐scale finite‐sum minimization on Riemannian manifold. We develop a sub‐sampled adaptive trust region method on Riemannian manifolds. Based on inexact ...information, we adopt adaptive techniques to flexibly adjust the trust region radius in our method. We present the iteration complexity is when the algorithm attains an ‐second‐order stationary point, which matches the result on trust region method. Numerical results for PCA on Grassmann manifold and low‐rank matrix completion are reported to demonstrate the effectiveness of the proposed Riemannian method.
An efficient and reliable method based on gas chromatography–mass spectrometry (GC–MS) was developed for the extraction and analysis of six phenolic endocrine disrupting chemicals (EDCs), such as ...4-nonylphenol (4-NP), nonylphenol-mono-ethoxylate (NP1EO), nonylphenol-di-ethoxylate (NP2EO), 4-
tert
-octylphenol (4-
t
-OP), bisphenol A (BPA) and 4-cumylphenol (4-CP) in surface water and sediment. The method was developed by using microwave-assisted extraction (MAE), solid phase extraction (SPE) and derivatization procedure. The MAE procedures were performed by optimizing three key process factors, consisted of extraction solvent, extraction temperature and holding time, affecting the extraction efficiency from sediment samples. For SPE, various parameters that may affect the recovery efficiency of water samples, such as SPE phase cartridge, elution solvent, as well as pH of water samples, were investigated. A series of derivatization conditions, such as derivatization reagent, reaction temperature and reaction time, were improved. The method achieved good repeatability and reproducibility with relative standard deviations <13% for all target EDCs in the both samples. Satisfactory recoveries for spiked water and sediment samples ranged from 85 to 101% and 74 to 105%, respectively. The limits of quantification varied from 0.20 (4-
t
-OP) to 11.50 ng L
−1
(NP2EO) and from 0.31 (4-
t
-OP) to 9.50 ng g
−1
dry weight (dw) (NP2EO) for water samples and sediment samples, respectively. The established method was successfully applied to the analysis of target EDCs in surface water and sediment samples collected from Caohai site of Dianchi Lake, China. The results showed that NP1EO, NP2EO and BPA were the three dominant phenolic EDCs in the site, reaching 114, 97 and 149 ng L
−1
in surface water, while 444, 186 and 178 ng g
−1
dw in surface sediment, respectively.
We propose an adaptive trust-region method for Riemannian optimization problems. Especially, the trust-region radius converges to zero with the adaptive technique, and the trust-region subproblem is ...solved by the truncated three-term conjugate gradient method with new restart strategies. We present some properties of this Riemannian method and establish the global convergence and local superlinear convergence under some mild assumptions. Numerical results for the Rayleigh quotient minimization problem, Principal Component Analysis problem, and joint diagonalization problem are reported to demonstrate the effectiveness of the proposed Riemannian method.
Tumour cells, stromal cells and the stroma comprise the tumour microenvironment. The metabolism of both tumour cells and several types of tumour stromal cells, such as cancer‐associated fibroblasts ...and tumour‐associated macrophages, is reprogrammed. Current studies have found that stromal cells promote tumour progression and metastasis, through not only the paracrine secretion of cytokines or chemokines, but also intermediate metabolites. Here, we summarize the latest insights into the mechanism of metabolic reprogramming in cancer cells, cancer‐associated fibroblasts and tumour‐associated macrophages, and their potential roles in tumour progression and metastasis.
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