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PurposeOcular pathology may be reduced by slowing myopia progression. The purpose of this study was to evaluate the potential of a novel custom-designed rigid gas permeable (RGP) contact lens to control high myopia by comparing the efficacy of multifocal RGP lenses and single-vision spectacles for high myopia control.MethodsThe medical records of children fitted with spectacles or multifocal rigid gas-permeable lenses between January 2018 and May 2020 were retrospectively reviewed. Children (5–17 years) with non-cycloplegic spherical equivalent refraction of ≤ −6.00 D or spherical equivalent refraction > − 6.00 D with baseline axial length ≥ 26.5 mm, and astigmatism of ≥ −2.00 D were included. Axial length and refraction were measured at baseline, before fitting the participants with multifocal rigid gas-permeable lenses or spectacles, and at 1- and 2-year follow-up visits. Changes in axial length were compared between the groups.ResultsAmong the 77 children with 1-year follow-up data, the mean axial elongation was 0.20 ± 0.17 mm and 0.21 ± 0.14 mm in the multifocal rigid gas-permeable and control groups, respectively, without significant differences between groups (F = 0.004, p = 0.835). Among the 41 patients who completed 2 years of follow-up, the mean axial elongation values in the multifocal rigid gas-permeable and control groups were 0.21 ± 0.15 mm and 0.24 ± 0.13 mm, respectively, at the 1-year follow-up, and 0.37 ± 0.27 mm and 0.43 ± 0.23 mm, respectively, at the 2-year follow-up, without significant between-group differences at either time point (p = 0.224).ConclusionAxial length increased at a similar rate in both the control (spectacles) and multifocal rigid gas-permeable lens groups, suggesting that multifocal rigid gas-permeable lenses have no significant impact on controlling high myopia progression compared with spectacles.

Network fingerprinting detection is an important network reconnaissance method,which can be used by attackers to obtain the fingerprinting characteristics of the target network,and then provide support for subsequent targeted attacks.Fingerprinting obfuscation technology enables attackers to form fake fingerprinting views by actively modifying the fingerprinting features in response packets.However,existing obfuscation methods are still insufficient in dealing with attackers’ strategic detection and analysis.To this end,a differential privacy based fingerprinting obfuscation mechanism(DPOF) towards network reconnaissance deception is proposed.Taking the idea of data privacy protection as a reference,DPOF first establishes a utility-driven differential privacy fingerprinting obfuscation model,and calculates the obfuscation probability of fake fingerprints with different utilities through the differential privacy exponential mechanism.On this basis,a fingerprinting obfuscation decision method under resource constraint is further designed,and an obfuscation strategy solving algorithm based on particle swarm optimization is implemented.Simulation results show that compared with the existing typical fingerprinting obfuscation methods,DPOF has better fingerprinting obfuscation effect with different problem scales and budgets,and can obtain a better approximate optimal strategy at a faster speed.

Background: The excessive activation of the microglia leads to the release of inflammatory factors that contribute to neuronal cell loss and neurodegeneration in Parkinson's Disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) that belongs to a newly found neurotrophic factors (NTFs) family has been reported to promote neuronal survival in the PD models. However, the effects of the MANF on neuroinflammation in PD remain unclear. Methods: AAV8-MANF virus was constructed to determine whether the high expression of MANF can protect the neuroinflammation-induced dopaminergic neurodegeneration in rats with 6-OHDA-induced PD. Rotarod performance test, immunofluorescent staining and western bolt were employed to evaluate the behavioral dysfunction, dopaminergic neurodegeneration, microglia activation, and signal activation. 6-OHDA treated SH-SY5Y cells and LPS treated BV-2 cells were used as the in vitro model for MANF neuroprotective and neuroinflammation mechanisms. Cell vitality and apoptosis were evaluated with MTT, CCK-8 and flow cytometric analysis. The AKT/GSK3β-Nrf2 signaling and the TNF-α/IL6 expression were measured by Western Blot. Results: Our findings indicated that the elevated MANF expression by the AAV8-MANF administration ameliorated the motor dysfunction and protected the dopaminergic neurons in the 6-OHDA treated rats. The upregulated CD11b in the rat SN caused by the 6-OHDA administration was significantly attenuated by the pretreatment of the AAV8-MANF. Furthermore, the levels of p-AKT, p-GSK3β, BCL-2, and Nrf-2 were upregulated by the high expression of the MANF. Under the oxidative stress of the 6-OHDA, the MANF significantly reduced the apoptotic effect of the TNF-α on the SH-SY5Y cells. In the LPS treated BV-2 cells, the MANF reduced the production of the TNF-α and IL-6, via enhancing the Nrf-2, p-Akt, p-GSK3β, and p-NF-κβ level. Conclusions: These results suggested that the MANF prevented the dopaminergic neurodegeneration caused by the microglia activation in PD via activation of the AKT/GSK3β-Nrf-2 signaling axis.

Background: The gut microbiota is crucial in the process of radiation enteritis (RE). Asrecommended by Chinese expert consensus, three formulas such as Baitouweng decoction, Gegen Qinlian decoction, and Shaoyao decoction, are used to prevent the same type of RE. Methods: Herein, we aimed to investigate the common pharmaceutical ingredients andmolecular mechanisms of the three formulas on RE from the perspective of gut microbiotathrough multi-bioinformatics analysis and mouse experiment. Results: Interestingly, theimportant active ingredient screened was quercetin in all three herbal formulas, andthedominant targets that participated in RE treatment by targeting gut microbiota regulationwere IL10, STAT1, IL1B, and IL1A. The concentration of quercetin was measured inGegenQinlian decoction > Shaoyao decoction > Baitouweng decoction (P <0.001) usinghighperformance liquid chromatography. Moreover, a total of 40 SPF C57/BL6J (male, 12–14weeks old) mice were assigned to perform the validation experiment with various quercetinintervention doses. Quercetin significantly protected against inflammatory responseinradiation induced-mice. The microbial alterations in the gut caused by quercetinintervention in radiation-induced mice were also explained. We further confirmedthealterations in the relative mRNA expression of the three formulas for the treatment of RE, which have four similar gut microbiota-regulated targets (IL10, STAT1, IL1B, andIL1A). Conclusion: These findings show that quercetin regulated the gut microbiota for REtherapy, a connotation that works on the principle of “different treatments for the samedisease” for RE. The present investigation provides methodological guidelines and protocolsfor the modern use and examination of traditional therapeutic concepts. [ABSTRACT FROM AUTHOR]

To analyze nonlinear dynamic systems, we developed a new technique based on the square matrix method. We propose this technique called the “convergence map” for generating particle stability diagrams similar to the frequency maps widely used in accelerator physics to estimate dynamic aperture. The convergence map provides similar information as the frequency map but in a much shorter computing time. The dynamic equation can be rewritten in terms of action-angle variables provided by the square matrix derived from the accelerator lattice. The convergence map is obtained by solving the exact nonlinear equation iteratively by the perturbation method using Fourier transform and studying convergence numerically. When the iteration is convergent, the solution is expressed as a quasiperiodic analytical function as a highly accurate approximation and hence the motion is stable. The border of stable motion determines the dynamical aperture. As an example, we applied the new method to the nonlinear optimization of the NSLS-II storage ring and demonstrated a dynamic aperture comparable to or larger than the nominal one obtained by particle tracking. The computation speed of the convergence map is 30 to 300 times faster than the speed of the particle tracking, depending on the size of the ring lattice (number of superperiods). The computation speed ratio is larger for complex lattices with low symmetry, such as particle colliders.

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BKCa) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BKCa channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BKCa currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BKCa channels, resulting in the TN.

Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K) and phosphatase and tensin homologue deleted on chromosome ten (PTEN), and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1) protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ), an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC) significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2) cells compared with the negative control HepG2 (NC-HepG2) cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1) significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. Keywords: Alcoholic fatty liver, Protein kinase B, Cytochrome P4502E1, Oxidative stress, Insulin-like growth factor-1

In order to realize the resource utilization of calcite tailings corner waste, block copolymerized polypropylene (PPB)/polyolefin elastomer (POE)/calcite waste powder ternary composites were prepared by melt blending modified extrusion method. The effects of waste powder content and POE content on mechanical properties, thermal properties and microstructure of composites were investigated. The results show that POE can improve compatibility of composites, and calcite waste powder can significantly enhance stiffness. Adding 10 phr of calcite waste powder and 20 phr of POE to the PPB base material can improve compatibility between inorganic filler and resin substrate and significantly improve mechanical properties of composites. The impact strength of composites is increased to 55.48 kJ/m2 by the coordination of calcite waste powder and POE. POE and calcite waste powder both reduce the crystallinity of composites, have little effect on melting temperature, and slightly increase crystallization temperature. PPB, POE and calcite waste powder are compounded to prepare composites, which provided a new way to solve the application problem of calcite tailings. [ABSTRACT FROM AUTHOR]

In recent years, water (R718) as a kind of natural refrigerant—which is environmentally-friendly, safe and cheap—has been reconsidered by scholars. The systems of using water as the refrigerant, such as water vapor compression refrigeration and heat pump systems run at sub-atmospheric pressure. So, the research on water boiling heat transfer at sub-atmospheric pressure has been an important issue. There are many research papers on the evaporation of water, but there is a lack of data on the characteristics at sub-atmospheric pressures, especially lower than 3 kPa (the saturation temperature is 24 °C). In this paper, the experimental research on water boiling heat transfer on a horizontal copper rod surface at 1.8–3.3 kPa is presented. Regression equations of the boiling heat transfer coefficient are obtained based on the experimental data, which are convenient for practical application.

To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms. At the end of the study (21 weeks), GO administration significantly inhibited the increase of the nodule incidence and average nodule number per nodule-bearing liver induced by NDEA, improved hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of serum biochemical indices (alanine aminotransferase , aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl, andβ-arrestin-2 were significantly decreased whereas those of Bax and caspase-3 were significantly increased. These data suggest that GO exhibited significant protection against NDEA-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.

With the aid of machine learning techniques, the genetic algorithm has been enhanced and applied to the multi-objective optimization problem presented by the dynamic aperture of the National Synchrotron Light Source II (NSLS-II) Storage Ring. During the evolution processes employed by the genetic algorithm, the population is classified into different clusters in the search space. The clusters with top average fitness are given “elite” status. Intervention on the population is implemented by repopulating some potentially competitive candidates based on the experience learned from the accumulated data. These candidates replace randomly selected candidates among the original data pool. The average fitness of the population is therefore improved while diversity is not lost. Maintaining diversity ensures that the optimization is global rather than local. The quality of the population increases and produces more competitive descendants accelerating the evolution process significantly. When identifying the distribution of optimal candidates, they appear to be located in isolated islands within the search space. Some of these optimal candidates have been experimentally confirmed at the NSLS-II storage ring. The machine learning techniques that exploit the genetic algorithm can also be used in other population-based optimization problems such as particle swarm algorithm.

The nonlinear dynamics of a system with periodic structure can be analyzed using a square matrix. We show that because of the special property of the square matrix constructed for nonlinear dynamics, we can reduce the dimension of the matrix from the original large number for high order calculations to a low dimension in the first step of the analysis. Then a stable Jordan decomposition is obtained with much lower dimension. The Jordan decomposition leads to a transformation to a new variable, which is an accurate action-angle variable, in good agreement with trajectories and tune obtained from tracking. More importantly, the deviation from constancy of the new action-angle variable provides a measure of the stability of the phase space trajectories and tune fluctuation. Thus the square matrix theory shows a good potential in theoretical understanding of a complicated dynamical system to guide the optimization of dynamical apertures. The method is illustrated by many examples of comparison between theory and numerical simulation. In particular, we show that the square matrix method can be used for fast optimization to reduce the nonlinearity of a system.

BackgroundDetecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis.MethodsMTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells.ResultsDoxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites.ConclusionDoxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells.