Although bioinert titanium has been widely applied in orthopedics and related fields, its usage is limited by its unsatisfying osteoinductivity, anti-infection capability, and wear-resistance. ...Osteoinductive apatite coating can be fabricated on a titanium surface by electrochemical methods, but this causes bacterial adhesion and poor wear-resistance. On the basis of pulse electrochemical technology, a wear-resistance and antibacterial osteoinductive coating was fabricated through codeposition of hydroxyapatite (HA) and nano-Ag effectuated by the cohybridization ofchitosan (CS) with Ag+ and Ca2+. A composite coating formed with uniformly dispersed spherical nanoparticles was obtained at optimized deposition potential, Ag concentration, and apatite concentration. The nanocomposite coating shows excellent bioinductive activity; it promotes preferential growth on the (002) face, and needle-like ordered arrangement of apatite. Due to the mediation of CS hybridization, a compact structure is achieved in the HA/Ag composite coating which significantly enhances the wear-resistance of the coating and reduces the release of Ca2+ and Ag+. The antibacterial rate of the coating on Escherichia coli and Staphylococcus aureus is up to 99% according to the antibacterial test. In conclusion, a wear-resistant and long-term antibacterial bioactive nanocomposite coating is successfully fabricated on titanium surface through the strategy established in this study.
Although adaptive control design with function approximators, for example, neural networks (NNs) and fuzzy logic systems, has been studied for various nonlinear systems, the classical adaptive laws ...derived based on the gradient descent algorithm with <inline-formula> <tex-math notation="LaTeX">{\sigma } </tex-math></inline-formula>-modification or <inline-formula> <tex-math notation="LaTeX">{e} </tex-math></inline-formula>-modification cannot guarantee the parameter estimation convergence. These nonconvergent learning methods may lead to sluggish response in the control system and make the parameter tuning complex. The aim of this paper is to propose a new learning strategy driven by the estimation error to design the alternative adaptive laws for adaptive control of nonlinear servo systems. The parameter estimation error is extracted and used as a new leakage term in the adaptive laws. By using this new learning method, the convergence of both the estimated parameters and the tracking error can be achieved simultaneously. The proposed learning algorithm is further tailored to retain finite-time convergence. To handle unknown nonlinearities in the servomechanisms, an augmented NN with a new friction model is used, where both the NN weights and some friction model coefficients are estimated online via the proposed algorithms. Comparisons with the <inline-formula> <tex-math notation="LaTeX">{\sigma } </tex-math></inline-formula>-modification algorithm are addressed in terms of convergence property and robustness. Simulations and practical experiments are given to show the superior performance of the suggested adaptive algorithms.
Greenhouse gas reduction requires joint efforts from the global society, while improving CO2 emission efficiency is a centrally important means to realize emission reduction targets. Therefore, it is ...of strategic importance to identify main influential factors to CO2 emission efficiency of different countries by considering the technology heterogeneity. The originality herein lies in that, applying the modified decomposition method of Metafrontier Malmquist Luenberger Index (MML) to define the priority of contracting countries in Paris Agreement to improve emission efficiency. In this study, 97 contracting countries of Paris Agreement are divided into 4 groups according to levels of income (low-income countries, lower-middle income countries, upper-middle income countries and high-income countries), and studied with their input and output data during 1990–2014 as samples. The empirical results reveal that the paths for the contracting countries of Paris Agreement to improve the efficiency are different: first, lower-middle income group can be facilitated through increasing factor input to increase the MML index considering the highest increase in scale efficiency (2.78%). Second, low-income group should eliminate the excessive concentration of inputs by enhancing the energy management efficiency. Third, in terms of the significant advancement of high-income group's MML index brought by technology advancement and the abnormal drop of Brunei Darussalam's MML related to technology decay, this analysis emphasized that the advancement and innovation of energy technology are the main force for total-factor CO2 emission efficiency improvement.
•The decomposition of Metafrontier Malmquist Luenberger is developed into 8 aspects.•The decomposition result can guide the countries to improve CO2 emission efficiency.•An empirical analysis on contracting countries in Paris Agreement is constructed.•The progress of energy technology is vital for CO2 emission efficiency improvement.
Although studies have investigated the role of gamma-aminobutyric acid (GABA)ergic signaling in rodent neural development and behaviors relevant to autism, behavioral ontogeny, as underlain by the ...changes in GABAergic system, is poorly characterized in different brain regions. Here, we employed a valproic acid (VPA) rat model of autism to investigate the autism-like behaviors and GABAergic glutamic acid decarboxylase 67 (GAD67) expression underlying these altered behaviors in multiple brain areas at different developmental stages from birth to adulthood. We found that VPA-treated rats exhibited behavioral abnormalities relevant to autism, including delayed nervous reflex development, altered motor coordination, delayed sensory development, autistic-like and anxiety behaviors and impaired spatial learning and memory. We also found that VPA rats had the decreased expression of GAD67 in the hippocampus (HC) and cerebellum from childhood to adulthood, while decreased GAD67 expression of the temporal cortex (TC) was only observed in adulthood. Conversely, GAD67 expression was increased in the prefrontal cortex (PFC) from adolescence to adulthood. The dysregulated GAD67 expression could alter the excitatory-inhibitory balance in the cerebral cortex, HC and cerebellum. Our findings indicate an impaired GABAergic system could be a major etiological factor occurring in the cerebral cortex, HC and cerebellum of human cases of autism, which suggests enhancement of GABA signaling would be a promising therapeutic target for its treatment.
Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. ...However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H
clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation.
Autophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription-PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues.
Autophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3).
Activation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.
An emerging industry refers to an aggregation of sectors and firms that create disruptive technologies and/or huge market potentials. Emerging industries based on technological innovation have ...increasingly become an important driving force for industrial competitiveness and economic growth. Although regional innovation systems (RISs) boost regional industries, it remains under-investigated whether and how RISs have differential impacts on different industries. Inspired by Pavitt's taxonomy of sectorial innovation, we propose four paradigms of industrial innovation in the context of emerging industries in China. We also empirically explore the effects of RISs on emerging industries, distinguishing the short-term effects from long-term ones. We present two key findings. First, RISs have generally contributed to the growth of emerging industries in China. Second, different components of RISs have varied impacts on different emerging industries. The results provide both theoretical underpinnings and empirical evidence for policy-makers, suggesting that well-designed policies that leverage RIS formation and regional industry specific characteristics are vitally important for development of emerging industries. Our study makes three important contributions. First, it theorizes a conceptual framework on possible mechanism through which RISs promote emerging industries. Second, this study sheds empirical light on both short-term and long-term effects of individual RIS components on seven emerging industries in the Chinese context. Third, the paper proposes four paradigms of industrial innovation in emerging industries under the RIS framework.
•Mechanisms of linking regional innovation systems (RIS) and emerging industries are theoretically established.•This paper presents empirical evidence on strong linkages between RIS and emerging industries in China.•Industry-specific characteristics are embedded with the effect of RIS on different typical emerging industries in China.•Four innovation paradigms in emerging industries are identified.
The 2D computational fluid dynamics (CFD) model of transmission conductor is set up to simulate the aerodynamic forces varying with time on the conductor. Taking into account the geometrical ...nonlinearity of conductor lines, the finite element (FE) models of single span and two-span transmission lines discretized with beam elements are established. By means of the FE models, the aeolian vibrations of the conductor lines excited by the aerodynamic forces under different wind velocities are numerically simulated. The nonlinear resonant characteristics, the amplitude-frequency relations of the conductor lines during aeolian vibration are investigated, and the influences of the span length as well as the initial tension in conductors on the aeolian vibration characteristics are analyzed. Furthermore, a 3D FE model of a conductor segment and the suspension clamp is created to study the stress distributions of the 3D model corresponding to different lines during aeolian vibrations. Finally, based on the stress analysis of the 3D model, the fatigue lives of the transmission conductors during aeolian vibration under different wind velocities are estimated. The jump phenomenon induced by the nonlinear vibration is reflected by the numerical simulation considering the geometric nonlinearity, and it is found that the energy balance principle (EBP) overestimates the vibration amplitudes because it cannot take the influences of the geometrical nonlinearity and span length into account. The obtained results may provide some instructions for the prevention design of aeolian vibration.
Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, ...we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal.
We did an epidemiology comparative study to investigate: annual production and sales of colistin in agriculture across mainland China according to data from the China Veterinary Drug Association from 2015 to 2018; the prevalence of colistin-resistant E coli (CREC) in pigs and chickens in 23 Chinese provinces and municipalities as reported in the China Surveillance on Antimicrobial Resistance of Animal Origin database from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2017, to Dec 31, 2018; the presence of residual colistin and mcr-1 in faeces from 118 animal farms (60 pig, 29 chicken, and 29 cattle) across four provinces over July 1, 2017, to August 31, 2017, and July 1, 2018 to August 31, 2018; the prevalence of mcr-1-positive E coli (MCRPEC) carriage in healthy individuals attending routine hospital examinations across 24 provinces and municipalities from June 1 to July 30, 2019, comparing with equivalent 2016 data (June 1 to September 30) from our previous study in the same hospitals; and the patterns in CREC prevalence among hospital E coli infections across 26 provinces and municipalities from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2018, to Dec 31, 2019, reported on the China Antimicrobial Surveillance Network.
After the ban on colistin as a growth promoter, marked reductions were observed in the production (27 170 tonnes in 2015 vs 2497 tonnes in 2018) and sale (US$71·5 million in 2015 vs US$8·0 million in 2018) of colistin sulfate premix. Across 118 farms in four provinces, mean colistin residue concentration was 191·1 μg/kg (SD 934·1) in 2017 versus 7·5 μg/kg (50·0) in 2018 (p<0·0001), and the median relative abundance of mcr-1 per 16S RNA was 0·0009 IQR 0·0001–0·0059 in 2017 versus 0·0002 0·0000–0·0020 in 2018 (p=0·0001). Across 23 provinces and municipalities, CREC was identified in pig faeces in 1153 (34·0%) of 3396 samples in 2015–16 versus 142 (5·1%) of 2781 in 2017–18 (p<0·0001); and in chickens in 474 (18·1%) of 2614 samples in 2015–16 versus 143 (5·0%) of 2887 in 2017–18 (p<0·0001). In hospitals across 24 provincial capital cities and municipalities, human carriage of MCRPEC was identified in 644 (14·3%) of 4498 samples in 2016 versus 357 (6·3%) of 5657 in 2019 (p<0·0001). Clinical CREC infections in 26 provinces and municipalities comprised 1059 (1·7%) of 62 737 E coli infections in 2015–16 versus 794 (1·3%) of 59 385 in 2018–19 (p<0·0001).
The colistin withdrawal policy and the decreasing use of colistin in agriculture have had a significant effect on reducing colistin resistance in both animals and humans in China. However, continuous colistin monitoring is essential, in particular to act as an early warning system for colistin stewardship in Chinese hospitals.
National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.
Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation ...pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression. Video Abstract.
Notoginsenoside R1 (NGR1) is a predominant phytoestrogen extracted from
Panax notoginseng
that has recently been reported to play important roles in the treatment of cardiac dysfunction, diabetic ...kidney disease, and acute liver failure. Studies have suggested that NGR1 may be a viable treatment of hypoxic-ischemic brain damage (HIBD) in neonates by reducing endoplasmic reticulum stress via estrogen receptors (ERs). However, whether NGR1 has other neuroprotective mechanisms or long-term neuroprotective effects is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL) in 7-day-old postnatal Sprague Dawley (SD) rats followed by exposure to a hypoxic environment were used to mimic an HIBD episode. We assessed the efficacy of NGR1 by measuring neuronal damage with MTT assay and assessed brain injury by TTC staining and brain water content detection 24–48 h after OGD/HIE. Simultaneously, we measured the long-term neurophysiological effects using the beam walking test (5 weeks after HI) and Morris water maze test 5–6 weeks after HI. Expression of PI3K-Akt-mTOR/JNK (24 h after HI or OGD/R) proteins was detected by Western blotting after stimulation with HI, NGR1, LY294002 (PI3K inhibitor), 740Y-P (PI3K agonist), or ICI 182780(estrogen receptors inhibitor). The results indicated that NGR1 exerted neuroprotective effects by inhibiting neuronal apoptosis and promoting cell survival via the PI3K-Akt-mTOR/JNK signaling pathways by targeting ER in neonatal hypoxic–ischemic injury.
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