Turning bad into good: A medium-entropy double perovskite oxide with beneficial surface reconstruction for active and robust cathode of solid oxide fuel cells.

The cathodes of solid oxide fuel cells (SOFCs) often suffer from detrimental cation segregations and associated impurities poisoning, leading to insufficient electroactivity and poor stability. Here we developed a medium-entropy double perovskite GdBa(Co1.2Mn0.2Fe0.2Ni0.2Cu0.2)O5-δ (ME-GBCO) for promising SOFC cathode. The increased configuration entropy can effectively tailor the surface composition with in situ formed active BaCoO3-δ (BCO) species, rather than inert and deleterious BaOx segregation on parent GdBaCo2O5-δ (GBCO) surface. Accordingly, the layered ME-GBCO cathode with beneficial surface reconstruction exhibited not only high oxygen reduction activity but excellent durability against CO2 impurity, enabling it a very attractive cathode for intermediate temperature SOFCs (IT-SOFCs). Our study provides a new idea for development of efficient and durable cathodes via configurational entropy induced rational surface reconstruction.

ResGEM: Multi-scale Graph Embedding Network for Residual Mesh Denoising.

Mesh denoising is a crucial technology that aims to recover a high-fidelity 3D mesh from a noise-corrupted one. Deep learning methods, particularly graph convolutional networks (GCNs) based mesh denoisers, have demonstrated their effectiveness in removing various complex real-world noises while preserving authentic geometry. However, it is still a quite challenging work to faithfully regress uncontaminated normals and vertices on meshes with irregular topology. In this paper, we propose a novel pipeline that incorporates two parallel normal-aware and vertex-aware branches to achieve a balance between smoothness and geometric details while maintaining the flexibility of surface topology. We introduce ResGEM, a new GCN, with multi-scale embedding modules and residual decoding structures to facilitate normal regression and vertex modification for mesh denoising. To effectively extract multi-scale surface features while avoiding the loss of topological information caused by graph pooling or coarsening operations, we encode the noisy normal and vertex graphs using four edge-conditioned embedding modules (EEMs) at different scales. This allows us to obtain favorable feature representations with multiple receptive field sizes. Formulating the denoising problem into a residual learning problem, the decoder incorporates residual blocks to accurately predict true normals and vertex offsets from the embedded feature space. Moreover, we propose novel regularization terms in the loss function that enhance the smoothing and generalization ability of our network by imposing constraints on normal consistency. Comprehensive experiments have been conducted to demonstrate the superiority of our method over the state-of-the-art on both synthetic and real-scanned datasets.

The clinical course of untreated CIN2 (HPV16/18+) under active monitoring: A protocol of systematic reviews and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most prevalent and fatal cancers among women. Nearly all forms of CC are related to HPV, and 70% of invasive CCs are associated with HPV16 and HPV18. A histologically confirmed case of cervical intraepithelial neoplasia (CIN)2 or a more severe histological diagnosis is considered to be the demarcation point for treatment, but overtreatment will increases the risk of preterm birth in subsequent pregnancies. This study will evaluate the progress of CIN2 (progression, persistence, or regression) in HPV16/18+ CIN2 patients who were managed conservatively for 3 months. METHODS: PubMed, Cochrane Library, China National Knowledge Infrastructure, Cumulative Index for Nursing and Allied Health Literature (CINAHL), and the Excerpta Medica Database will be searched. We will include studies reporting on women with CIN2 and HPV16/18+, conservative treatment for 3 to 60 months with disease outcomes including progression (CIN3 or worse), persistence (CIN2), and regression rates (CIN1 or less). The primary outcome will be the progress of CIN2. Two authors will search the relevant literature, extract the data, and assess the risk of bias. A funnel chart will be used to identify publication or other reporting biases, and the AHRQ guidelines will be used to assess the risk of bias in each included study. The I2 statistic will be used to assess heterogeneity. If there is a high degree of heterogeneity between the studies, the random effects model will be used; otherwise, a fixed effects model will be used. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will evaluate the clinical development of patients with conservatively monitored histologically confirmed HPV16/18+ CIN2.

Applied research on confocal microscopy through focusing detection of tarsal glands shape following phacoemulsification for cataract.

OBJECTIVE: To investigate the value of confocal microscopy in determining the morphology of the tarsal gland after cataract phacoemulsification. METHODS: A total of 74 patients (74 eyes) who underwent phacoemulsification for a monocular cataract and intraocular lens implantation (all were single eye surgeries) in our hospital from May 2018 to October 2018 were recruited as the study cohort, with 43 male patients and 31 female patients, and a mean age of (64.8±12.5) years old. All the patients were followed up for 6 months, of whom 25 cases with MGD were included in the MGD group and 49 cases without MGD were included in the control group. All the patients were examined within 30 days and underwent IVCM inspections of the acinar morphology of the tarsal glands (expansion and atrophy), the infiltration of the inflammatory cells in the tarsal gland tissue, and a classification of the fibrosis in the tarsal gland tissue. RESULTS: The longest and shortest acinar diameters in the MGD patients were significantly greater than they were in the control group, but the acinar areas were smaller than they were in the control group. The meibomian glandular vesicle densities, the average opening diameters, the fibrosis, and the inflammatory cell density in the MGD group were significantly increased. CONCLUSION: IVCM plays a vital role in the early diagnosis, in the severity grading, and in the evaluation of the clinical effectiveness of MGD-related diseases, by which the morphological changes of the tarsal gland after phacoemulsification can be observed in a timely manner to predict the occurrence of MGD.

HMEJ-based safe-harbor genome editing enables efficient generation of cattle with increased resistance to tuberculosis.

The CRISPR/Cas9 system has been used in a wide range of applications in the production of gene-edited animals and plants. Most efforts to insert genes have relied on homology-directed repair (HDR)-mediated integration, but this strategy remains inefficient for the production of gene-edited livestock, especially monotocous species such as cattle. Although efforts have been made to improve HDR efficiency, other strategies have also been proposed to circumvent these challenges. Here we demonstrate that a homology-mediated end-joining (HMEJ)-based method can be used to create gene-edited cattle that displays precise integration of a functional gene at the ROSA26 locus. We found that the HMEJ-based method increased the knock-in efficiency of reporter genes by eightfold relative to the traditional HDR-based method in bovine fetal fibroblasts. Moreover, we identified the bovine homology of the mouse Rosa26 locus that is an accepted genomic safe harbor and produced three live-born gene-edited cattle with higher rates of pregnancy and birth, compared with previous work. These gene-edited cattle exhibited predictable expression of the functional gene natural resistance-associated macrophage protein-1 (NRAMP1), a metal ion transporter that should and, in our experiments does, increase resistance to bovine tuberculosis, one of the most detrimental zoonotic diseases. This research contributes to the establishment of a safe and efficient genome editing system and provides insights for gene-edited animal breeding.

Arsenic-induced autophagy regulates apoptosis in AML-12 cells.

Arsenic (As), a potent toxicant, is known to be a hepatotoxicant. Although As induced liver apoptosis and autophagy, the relationship between apoptosis and autophagy of hepatocytes caused by As remains largely unknown. 3-methyladenine (3-MA) and rapamycin can inhibit and promote autophagy of AML-12 cells, respectively. Hence, in this study, AML-12 cells were treated with different concentrations (0, 2, 4, 6, 8, 10 and 12 µmol/L) of As2O3, and 5 mmol/L 3-MA or 100 nmol/L rapamycin were applied to distinguish the effect of autophagy on apoptosis in AML-12. Results showed that exposure to As induced cell apoptosis and autophagy, which were mediated by the significantly altered expression levels of autophagy markers (mTOR, LC3, PI3K and P62), and apoptosis markers (Bcl-2 and caspase-3). Further analysis indicated that a certain dosage of 3-MA and rapamycin decreased apoptosis and the caspase-3 expression, which suggested that As-induced autophagy regulated AML-12 cells apoptosis through the expressions of PI3K, mTOR, P62 and Bcl-2.

Effect of arsenic and/or fluoride gestational exposure on renal autophagy in offspring mice.

Both arsenic (As) and fluorine (F) are toxic substances widely found in the environment, which threaten to various organs of both human and animals, especially the kidney. In this study, to investigate the individual and combined effects of arsenic (15 mg/L As2O3(III)) and fluoride (100 mg/L NaF), arsenic (15 mg/L As2O3(III)) and fluoride-arsenic (15 mg/L As2O3(III)+100 mg/L NaF) on the renal autophagy during early life, a mouse model of gestationally exposed to As and/or F was established. The results showed that the mRNA expression levels of LC3, LC3I, LC3II, Beclin-1, ULK1, Atg13 and Atg14 were significantly increased with a concomitant decrease in mTOR and Bcl-2 up on individual exposure to As and F rather than in combined (As + F) exposure. In addition, the protein expression levels of LC3-II/LC3-I, Beclin-1, and LAMP1 were significantly increased with a concomitant decrease in mTOR and Bcl-2 in the mice subjected to individual exposure than the combined exposure. Based on the results, it was observed that renal tissue of mice was highly sensitive to F than As. Moreover, the toxicity of the combined (As + F) exposure was significantly lower than that of the individual exposure, which could be attributed due to the antagonism between As and F.

Interpreting and Extending the Guided Filter via Cyclic Coordinate Descent.

The guided filter (GF) is a widely used smoothing tool in computer vision and image processing. However, to the best of our knowledge, few papers investigate the mathematical connection between this filter and the least-squares optimization. In this paper, we first interpret the guided filter as the cyclic coordinate descent (CCD) solver of a least-squares objective function. This discovery implies an extension approach to generalize the guided filter since we can change the least-squares objective function and define new filters as the first pass iteration of the CCD solver of modified objective functions. In addition, referring to the iterative minimizing procedure of the CCD, we can derive new rolling filtering schemes. So, we are reasonable to say that our discovery not only reveals an approach to design new GF-like filters adapting to specific requirements of applications but also offers thorough explanations for two rolling filtering schemes of the guided filter as well as the method to extend them. Experiments prove our new proposed filters and rolling filtering schemes could produce state-of-the-art results.

Author Correction: Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

A photoluminescence "switch-on" nanosensor composed of nitrogen and sulphur co-doped carbon dots and gold nanoparticles for discriminative detection of glutathione.

Biological thiols play a key role in biological processes and are involved in a variety of diseases. The discriminative detection of biological thiols is still challenging. In this contribution, a platform, an energy transfer-based quenching system composed of nitrogen and sulphur co-doped carbon dots (N, S-CDs) and gold nanoparticles (AuNPs), was established to discriminate glutathione (GSH) from other competitive biothiols including cysteine (Cys) and homocysteine (Hcy) based on a photoluminescence (PL) "switch-on" signal readout. The presence of GSH can encapsulate AuNPs in priority because of the strong affinity towards AuNPs and the steric hindrance effect of GSH, leaving little chance for the N, S-CDs binding on the surface of AuNPs and thus resulting in the PL recovery of N, S-CDs. Compared with the nitrogen-doped carbon dots (N-CDs), the N, S-CDs can enhance 10 times sensitivity for the designed PL "switch-on" sensing strategy. The proposed method has a detection limit of 3.6 nM and can be successfully applied for the detection of GSH in human serum.

TGF-ß1 acts as mediator in fluoride-induced autophagy in the mouse osteoblast cells.

It is well known that excess fluoride intake can result in fluorosis, which is a serious public health problem. TGF-ß1 affects a wide variety of cellular activities and plays an important role in fluorosis. Recent literature proved that fluoride induces autophagy, however, the mechanism is still unclear, and the role of TGF-ß1 in the fluoride-induced autophagy should be further illustrated. Therefore, in this study, plasmids and small interfering RNA (siRNA) were used to overexpress and silence the TGF-ß1 expression in the osteoblasts cells. Our results demonstrated that sodium fluoride (NaF) (2.26 mg/L F-) exposure lead to a significant decrease in proliferation rate of mouse osteoblast cells in a dose-dependent manner with a concomitant increase in the expression levels of TGF-ß1 and autophagic markers. Overexpression of TGF-ß1 significantly increased the fluorescence intensity of MDCstained cells, the mRNA and protein expression levels of Beclin1 and LC3-II/I, with a concomitant decrease in p62. However, TGF-ß1 silencing resulted in vice versa. In summary, we concluded that TGF-ß1 plays a mediator role in NaF-induced autophagy of mouse osteoblast cells. In the future, TGF-ß1-autophagy signaling network could be a new idea for the investigation of skeletal fluorosis.

Optically Active Ultrafine Au-Ag Alloy Nanoparticles Used for Colorimetric Chiral Recognition and Circular Dichroism Sensing of Enantiomers.

Despite a significant surge in the number of investigations into chirality at the nanoscale, especially thiolated chiral molecules capping gold clusters, only limited knowledge is currently available to elaborate the alloying effect on chiroptical behavior of bimetallic nanoparticles (NPs). Also, few successful cases as to the efforts toward the development of chirality-dependent applications on the optically active nanomaterial have been made. Herein, as a positive test case for chiral alloy nanoparticle synthesis, the stable and large chiroptical ultrafine Au-Ag alloy NPs were prepared by reduction of different molar fractions of HAuCl4 and AgNO3 with NaBH4 in the presence of d/l-penicillamine (d/l-Pen). Compared with those of monometallic Au and Ag counterparts with comparable size, the Au-Ag alloy NPs (Ag mole fraction, 70%) obviously displayed the largest optical activities with the maximum g-factors of ∼1.6 × 10-3. Impressively, the Pen-mediated synthesis of chiral Au-Ag alloy NPs possesses a colorimetric self-recognition function and can be used as an incisive circular dichroism (CD) probe toward d- and l-Pen enantiomers. The plasmonic CD signal amplification (ΔICD) shows good linearity with the amount of Pen over the range of 5.0-80.0 µM with a detection limit (3σ) of 1.7 µM for l-Pen and 1.5 µM for d-Pen, respectively. In addition, the sensing system exhibits good selectivity toward d- and l-Pen in the presence of other enantiomers; therefore, it is highly expected that the approach described here would open new opportunities for design of more novel enantioselective analyses of important species related to biological processes.

Analysis of aqueous humor concentrations of cytokines in retinoblastoma.

To investigate the components of the aqueous humor (AH) in patients with retinoblastoma (RB). We collected 0.1 ml AH of 35 children with RB and 20 patients with congenital cataracts as controls. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 45 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. The concentrations of IL-6, IL-7, IL-8, IFN-γ, PIGF-1, VEGF-A, ß-NGF, HGF, EGF and FGF-2 were significantly higher in the AH of patients with RB than those in the control group (P<0.05). The study showed that the higher levels of IP-10, IL-6, IL-7, IL-8, IFN-γ, PIGF-1, VEGF-A, ß-NGF, HGF, EGF and FGF-2 in AH may be associated with RB. Our findings may facilitate a better understanding of the molecular pathways of tumors and solid molecular targets for new strategies for therapy and the earlier diagnosis of RB.

Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway.

Accumulation of mitochondrial reactive oxygen species (mROS) has been implicated in the pathogenesis of fluorosis. As the main mitochondrial deacetylase, SIRT3 is closely associated with oxidative stress. To investigate the role of SIRT3 in response to sodium fluoride (NaF)-induced nephrotoxicity. Our results showed that NaF treatment impaired mitochondrial ultrastructure, decreased cell viability and increased apoptosis in TCMK-1 cells. Oxidative stress, detected by mROS and 8-Hydroxy-2'-deoxyguanosine (8-OHdG) were higher in NaF-treated cells, accompanied by decreased level of reduced glutathione (GSH). NaF reduces manganese superoxide dismutase (SOD2) expression through SIRT3-mediated DNA-binding activity of FoxO3a and decrease SOD2 activity by inhibiting SIRT3-mediated deacetylation. These effects were ameliorated by overexpression of SIRT3. Peroxisome proliferator-activated receptor-coactivator 1a (PGC-1α) interacted with nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) that bound to SIRT3 promoter to regulate SIRT3 expression. The study provides new insights into a critical NRF2/PGC-1α-SIRT3 pathway in response to NaF-induced nephritic oxidative injury. In vivo treatment of SIRT3-expressing adenovirus protects against NaF-induced nephritic injury in mice. Moreover, mechanistic study revealed that ERK1/2 activation was associated with increased apoptosis induced by NaF. In conclusion, these data shedding light on new approaches for treatment of NaF-induced nephrotoxicity.

Speeding Up the Bilateral Filter: A Joint Acceleration Way.

Computational complexity of the brute-force implementation of the bilateral filter (BF) depends on its filter kernel size. To achieve the constant-time BF whose complexity is irrelevant to the kernel size, many techniques have been proposed, such as 2D box filtering, dimension promotion, and shiftability property. Although each of the above techniques suffers from accuracy and efficiency problems, previous algorithm designers were used to take only one of them to assemble fast implementations due to the hardness of combining them together. Hence, no joint exploitation of these techniques has been proposed to construct a new cutting edge implementation that solves these problems. Jointly employing five techniques: kernel truncation, best N-term approximation as well as previous 2D box filtering, dimension promotion, and shiftability property, we propose a unified framework to transform BF with arbitrary spatial and range kernels into a set of 3D box filters that can be computed in linear time. To the best of our knowledge, our algorithm is the first method that can integrate all these acceleration techniques and, therefore, can draw upon one another's strong point to overcome deficiencies. The strength of our method has been corroborated by several carefully designed experiments. In particular, the filtering accuracy is significantly improved without sacrificing the efficiency at running time.

Optically active red-emitting Cu nanoclusters originating from complexation and redox reaction between copper(ii) and d/l-penicillamine.

Despite a significant surge in the number of investigations into both optically active Au and Ag nanostructures, there is currently only limited knowledge about optically active Cu nanoclusters (CuNCs) and their potential applications. Here, we have succeeded in preparing a pair of optically active red-emitting CuNCs on the basis of complexation and redox reaction between copper(ii) and penicillamine (Pen) enantiomers, in which Pen serves as both a reducing agent and a stabilizing ligand. Significantly, the CuNCs feature unique aggregation induced emission (AIE) characteristics and therefore can serve as pH stimuli-responsive functional materials. Impressively, the ligand chirality plays a dramatic role for the creation of brightly emissive CuNCs, attributed to the conformation of racemic Pen being unfavorable for the electrostatic interaction, and thus suppressing the formation of cluster aggregates. In addition, the clusters display potential toward cytoplasmic staining and labelling due to the high photoluminescence (PL) quantum yields (QYs) and remarkable cellular uptake, in spite that no chirality-dependent effects in autophagy and subcellular localization are observed in the application of chiral cluster enantiomer-based cell imaging.

Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

PURPOSE: To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). METHODS: Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. RESULTS: In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). CONCLUSIONS: Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

Axial length measurements before and after removal of silicone oil: a new method to correct the axial length of silicone-filled eyes for optical biometry.

A total of 67 eyes of 67 patients that have undergone vitrectomy and silicone oil tamponade for rhegmatogenous retinal detachment were included in this prospective clinical study. We measured the axial length (AL) and the anterior chamber depth (ACD) with A-mode ultrasonography and IOL Master before and after removal of silicone oil. Phase refractive indices of silicone oil at different wavelengths from 400 nm to 1000 nm were measured with an Abbe refractometer and a series of equations were derived to adjust the AL values obtained with the IOL Master in silicone-filled eyes. The instruments showed good agreement between the AL values measured before and after removal of silicone oil. The ACD values obtained with A-mode ultrasonography were lower than the values obtained with the IOL Master (p < 0.01). The AL values obtained with the IOL Master after removal of silicone oil were lower than the values obtained preoperatively (p < 0.01). The AL values obtained with the IOL Master after adjustment are more accurate than A-mode ultrasonography in silicone-filled eyes.