Myopia is a leading cause of visual impairment in young people worldwide. It sometimes increases the risk of blindness and reduces life quality. Previous reports have revealed the treatment effects ...of defocus-incorporated multiple segments (DIMS) and topical atropine (ATP) on myopia control. However, no study has evaluated these two interventions together. In this retrospective study, we aimed to determine whether the combination of DIMS lenses and 0.01% ATP can slow the progression of myopia compared with DIMS lenses or single vision (SV) lenses alone. We included 107 children with myopia who were treated with DIMS and 0.01% ATP combination (DIMS + ATP group), DIMS monotherapy (DIMS group), or a control group (SV group). We compared treatment effects among three groups in axial length and myopia progression. After a 1-year follow-up, the DIMS + ATP group showed a smaller change in axial length and myopia progression than the DIMS and SV groups (P < 0.05). Hence, combination treatment with DIMS and 0.01% ATP might be a better choice for children with myopia.
The retinotectal synapse in larval zebrafish, combined with live time-lapse imaging, provides an advantageous model for study of the development and remodelling of central synapses in vivo. In ...previous studies, these synapses were labelled by transient expression of fluorescence-tagged synaptic proteins, which resulted in the dramatic variation of labelling patterns in each larva. Here, using GAL4-Upstream Activating Sequence (GAL4-UAS) methodology, we generated stable transgenic lines, which express EGFP-tagged synaptophysin (a presynaptic protein) in retinal ganglion cells (RGCs), to reliably label the pre-synaptic site of retinotectal synapses. This tool avoids the variable labelling of RGCs that occurs in transient transgenic larvae. We obtained several stable transgenic lines that differ consistently in the number of labelled RGCs. Using stable lines that consistently had a single labelled RGC, we could trace synaptogenic dynamics on an individual RGC axonal arbor across different developmental stages. In the stable lines that consistently had multiple labelled RGCs, we could simultaneously monitor both pre- and post-synaptic compartments by combining transient labelling of post-synaptic sites on individual tectal neurons. These tools allowed us to investigate molecular events underlying synaptogenesis and found that the microRNA-132 (miR-132) is required for developmental synaptogenesis. Thus, these transgenic zebrafish stable lines provide appropriate tools for studying central synaptogenesis and underlying molecular mechanisms in intact vertebrate brain.
Engineering nanoparticles of reasonable surface poly(ethylene glycol) (PEG) length is important for designing efficient drug delivery systems. Eliminating the disturbance by other nanoproperties, ...such as size, PEG density, etc., is crucial for systemically investigating the impact of surface PEG length on the biological behavior of nanoparticles. In the present study, nanoparticles with different surface PEG length but similar other nanoproperties were prepared by using poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymers of different molecular weights and incorporating different contents of PCL3500 homopolymer. The molecular weight of PEG block in PEG-PCL was between 3400 and 8000 Da, the sizes of nanoparticles were around 100 nm, the terminal PEG density was controlled at 0.4 PEG/nm2 (or the frontal PEG density was controlled at 0.16 PEG/nm2). Using these nanoproperties well-designed nanoparticles, we demonstrated PEG length-dependent changes in the biological behaviors of nanoparticles and exhibited nonmonotonic improvements as the PEG molecular weight increased from 3400 to 8000 Da. Moreover, under the experimental conditions, we found nanoparticles with a surface PEG length of 13.8 nm (MW = 5000 Da) significantly decreased the absorption with serum protein and interaction with macrophages, which led to prolonged blood circulation time, enhanced tumor accumulation and improved antitumor efficacy. The present study will help to establish a relatively precise relationship between surface PEG length and the in vivo behavior of nanoparticles.
The rational synthesis of single‐layer noble metal directly anchored on support materials is an elusive target to accomplish for a long time. This paper reports well‐defined single‐layer Pt (Pt‐SL) ...clusters anchored on ultrathin TiO2 nanosheets—as a new frontier in electrocatalysis. The structural evolution of Pt‐SL/TiO2 via self‐assembly of single Pt atoms (Pt‐SA) is systematically recorded. Significantly, the Pt atoms of Pt‐SL/TiO2 possess a unique electronic configuration with PtPt covalent bonds surrounded by abundant unpaired electrons. This Pt‐SL/TiO2 catalyst presents enhanced electrochemical performance toward diverse electrocatalytic reactions (such as the hydrogen evolution reaction and the oxygen reduction reaction) compared with Pt‐SA, multilayer Pt nanoclusters, and Pt nanoparticles, suggesting an efficient new type of catalyst that can be achieved by constructing single‐layer atomic clusters on supports.
Single‐layer Pt clusters, maintaining simultaneously adjacent Pt active atomic sites and PtPt covalent bonds, as a new frontier of atomic structure catalysts, are achieved by single Pt atoms self‐assembly. It exhibits unprecedented activity and stability toward diverse electrochemical reactions, such as hydrogen reduction reaction, oxygen reduction reaction, oxygen evolution reaction, and alcohol electrooxidation.
•More than 80% of COD, NH4+-N and TP were removed under OFL pressure.•OFL promoted the secretion of EPS and changed the EPS chemical composition.•OFL decreased the diversity and richness of the ...microbial community in the reactor.•OFL affected the read numbers of the functional bacteria community in the reactor.
An activated sludge sequencing batch reactor (SBR) was fed with synthetic wastewater containing ofloxacin (OFL) for 52days to study the overall performance of the SBR, the characteristics of extracellular polymeric substances (EPS) and the bacterial community shift. Removal efficiencies of chemical oxygen demand, ammonia nitrogen, phosphorus and OFL were maintained at 90%, 96%, 80% and 65%, respectively. The EPS contents increased with increasing OFL concentration because more EPS was secreted to protect cells from OFL damage. Moreover, the EPS compositions shifted. For denitrifying bacteria, the read number of Pseudomonas and Bacillus sharply decreased initially (p<0.05) and increased from Day 25 to Day 50, which agreed with the tendency of Nitrosomonadaceae (ammonia oxidizer), while Paracoccus significantly decreased (p<0.05). The read number of Rhodocyclaceae, a phosphorus-accumulating bacterium, increased. Other functional microbes such as Nitrospirales (nitrite oxidizer) and Planctomyces (anammox) sharply decreased under OFL pressure (p<0.05).
Ursolic acid (UA) has been reported to possess several biological benefits, such as anti-cancer, anti-inflammation, antibacterial, and neuroprotective functions. This study detects the function and ...molecular mechanism of UA in H9c2 cells under hypoxia and reoxygenation (H/R) conditions.Under H/R stimulation, the effects of UA on H9c2 cells were examined using ELISA and western blot assays. The Comparative Toxicogenomics Database was employed to analyze the target molecule of UA. Small interfering RNA was used to knock down CXCL2 expression, further exploring the function of CXCL2 in H/R-induced H9c2 cells. The genes related to the nuclear factor-kappa B (NF-κB) pathway were assessed using western blot analysis.Significant effects of UA on H/R-induced H9c2 cell damage were observed, accompanied by reduced inflammation and oxidative stress injury. Additionally, the increased level of CXCL2 in H/R-induced H9c2 cells was reduced after UA stimulation. Moreover, CXCL2 knockdown strengthened the beneficial effect of UA on H/R-induced H9c2 cells. HY-18739, an activator of the NF-κB pathway, can increase CXCL2 expression. Moreover, the increased levels of p-P65 NF-κB and p-IκBα in H/R-induced H9c2 cells were remarkably attenuated by UA treatment.In summary, the results indicated that UA may alleviate the damage of H9c2 cells by targeting the CXCL2/NF-κB pathway under H/R conditions.
The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by ...which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recogni- tion between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on py111z, the PEST domain of PTPN18 promotes K48-1inked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12.
The recognition of entanglement states is a notoriously difficult problem when no prior information is available. Here, we propose an efficient quantum adversarial bipartite entanglement detection ...scheme to address this issue. Our proposal reformulates the bipartite entanglement detection as a two-player zero-sum game completed by parameterized quantum circuits, where a two-outcome measurement can be used to query a classical binary result about whether the input state is bipartite entangled or not. In principle, for an N-qubit quantum state, the runtime complexity of our proposal is O(poly(N)T) with T being the number of iterations. We experimentally implement our protocol on a linear optical network and exhibit its effectiveness to accomplish the bipartite entanglement detection for 5-qubit quantum pure states and 2-qubit quantum mixed states. Our work paves the way for using near-term quantum machines to tackle entanglement detection on multipartite entangled quantum systems.
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