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Background: Amyloid-β (Aβ) is important in the etiology of Alzheimer’s disease (AD). Removal of Aβ from the brain is a major strategy for the prevention and treatment of AD. Objective: To clarify whether Aβ42 can be cleared by intestinal excretion and whether the gut microbiota (GM) can affect the excretory clearance of Aβ42 in the peripheral blood and intestines. Methods: Male 8-month-old C57BL6 mice were maintained on either normal chow or received broad-spectrum antibiotics in their drinking water for one week. Sterile saline, fluorescein isothiocyanate (FITC), or FITC-Aβ42 (fluorescein isothiocyanate-labeled amyloid-β42 peptides) was injected 1 h before sampling. Related changes of Aβ42 before and after injection were evaluated. Results: FITC-Aβ42 was injected into mice through the tail vein and could later be detected in feces. Furthermore, the fecal concentrations of FITC-Aβ42 were higher in mice that had been fed antibiotics to alter their GM than in normal mice. However, the FITC-Aβ42 concentrations in blood showed the opposite pattern. Conclusion: Aβ42 can be excreted into the intestinal lumen and is regulated by the GM.

Aiming at the problems of traditional equipment fault diagnosis, such as poor real-time performance, low efficiency and strong subjectivity, a method of industrial equipment sub-health status monitoring based on big data technology was proposed. Firstly, the characteristic engineering of vibration signals is formed by preprocessing vibration signals collected by sensors located near the bearing shaft. Then, the deep residual shrinkage network DRSN was used to build the classification model. By tuning the model parameters, the optimal sub-health status identification model of industrial equipment was obtained. Finally, the accuracy, robustness and generalization of the model were verified. Experimental results show that this method has better generalization performance and can significantly improve the accuracy of industrial equipment fault diagnosis, which has important theoretical value and practical significance to solve the sub-health problems of industrial equipment.

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft X-ray regime. We used the tri-cellulose acetate (C$_{9}$H$_{16}$O$_{8}$) foam of 2 mg/cm$^{-3}$ density, and $1$-mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. The plasma parameters were diagnosed to be T$_{e}$=17 eV and n$_{e}$=4 $\times$ 10$^{20}$ cm$^{-3}$. The average charge states passing through the plasma were observed to be higher than those predicted by the commonly-used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. In previsous measurement with partially ionized plasma from gas discharge and z-pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we were able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-Glass laser radiation. The finding is important for heavy ion beam driven high energy density physics and fast ignitions., Comment: 7 pages, 4 figures, 35 conferences

The massive release of pro-inflammatory cytokines is a crucial step in triggering the inflammatory cascade in sepsis. Exploring the key molecules regulating the expression and release of multiple cytokines has important value for revealing the mechanism of the cytokine storm in sepsis. This study aimed to investigate the role of multifunctional nuclear protein non-POU domain containing octamer-binding protein (NONO) in the sepsis cytokine storm and to elucidate the underlying mechanism. We found that NONO expression in tissues and cells of sepsis mice was significantly upregulated. Downregulation of NONO expression inhibited the mRNA expression of multiple cytokines, including IL-6, IL-1β, MCP-1, MIP-1α, and MIP-1β in inflammatory cells from mice and human leukemic monocyte-THP1 cells challenged with lipopolysaccharide (LPS), and significantly decreased the level of these cytokines and TNF-α in the supernatant of THP1 cells challenged by LPS. Nono knockout also reduced the levels of TNF-α, IL-6, MIP-1α, and MIP-1β in serum, alleviated hepatocyte edema, and improved the survival rate of sepsis mice. Reduced NONO expression decreased the phospho-ERK1/2 level in inflammatory cells from sepsis mice or THP1 cells challenged by LPS. Phospho-ERK1/2 inhibitor decreased the mRNA expression and concentration of cytokines in the culture supernatant of LPS-induced THP1 cells, similar to the effect of NONO knockdown. After LPS challenge, the levels of phospho-ERK1/2 and NONO were increased, with obvious colocalization in the nucleus and vesicular-like organelles in macrophages. NONO knockdown decreased nuclear translocation of phospho-ERK1/2 in LPS-challenged THP1 cells. These results suggest that NONO is a potentially critical molecule involved in multiple cytokine production in sepsis. Upregulated NONO in sepsis may promote the expression and release of multiple cytokines to participate in a sepsis cytokine storm by promoting ERK1/2 phosphorylation.

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of ∼222 eV for ∼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency η∼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.

Intense particle beams generated from the interaction of ultrahigh intensity lasers with sample foils provide options in radiography, high-yield neutron sources, high-energy-density-matter generation, and ion fast ignition. An accurate understanding of beam transportation behavior in dense matter is crucial for all these applications. Here we report the experimental evidence on one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter, in comparison with the current-widely used models describing individual ion stopping in matter. Supported by particle-in-cell (PIC) simulations, we attribute the enhancement to the strong decelerating electric field approaching 1 GV/m that can be created by the beam-driven return current. This collective effect plays the dominant role in the stopping of laser-accelerated intense proton beams in dense ionized matter. This finding is essential for the optimum design of ion driven fast ignition and inertial confinement fusion., A detailed understanding of particle stopping in matter is essential for nuclear fusion and high energy density science. Here, the authors report one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter in comparison with currently used models describing ion stopping in matter.

One of the most promising approaches to reach a high gain in inertial confinement fusion is the fast ignition scheme. In this scheme, a relativistic electron beam is generated; this passes through the imploded plasma and deposits parts of its energy in the core. However, the large angular spread of the relativistic electron beam and the poorly controlled compression of the target affect realization of the fast ignition technique. Here, we demonstrate that indirectly driven (that is, driven by X-rays generated inside a gold hohlraum) implosions with a ‘high-foot’ and a short-coast time of less than 200 ps allow us to tightly compress the shell. Furthermore, we show the ability to optimize the symmetry of the imploding shell by changing the hohlraum length, successfully tuning a suitable tube-shaped shell to compensate for the large angular spread of the relativistic electron beam and to enhance the electron-to-core coupling efficiency via resistive magnetic fields. Benefiting from those experimental techniques, a significant enhancement in neutron yield was achieved in our indirectly driven fast ignition experiments. These results pave the way towards high-coupling fast ignition experiments with indirectly driven targets similar to those at the National Ignition Facility. Experiments realizing the indirect-drive fast ignition scheme for inertial confinement fusion are reported. Enabled by a tightly compressed target, an increase of neutron yield is observed.

This study proposes an optimized algorithm for the navigation of the mobile robot in the indoor and dynamic unknown environment based on the decision tree algorithm. Firstly, the error of the yaw value outputted from IMU sensor fusion module is analyzed in the indoor environment; then, the adaptive FAST SLAM is proposed to optimize the yaw value from the odometer; in the next, a decision tree algorithm is applied which predicts the correct moving direction of the mobile robot through the outputted yaw value from the IMU sensor fusion module and adaptive FAST SLAM of the odometer data in the indoor and dynamic environment; the following is the navigation algorithm proposed for the mobile robot in the dynamic and unknown environment; finally, a real mobile robot is designed to verify the proposed algorithm.The final result shows the proposed algorithms are valid and effective.

Understanding the generation and evolution of magnetic fields in high-energy-density plasmas is a major scientific challenge in broad research areas including astrophysics, cosmology, and laser fusion energy. However, the fully three-dimensional (3D) topologies of such dynamic magnetic fields are still unknown yet. Here we report experiments of the first 3D synchronous proton radiography for self-generated magnetic fields in respectively laser-produced low-Z CH and high-Z Cu plasmas. The radiography images show that abundant 3D filamentary structures of magnetic fields grow up in coronal region of CH plasmas, while for Cu, the fields are majorly compressed along the dense surface region whose internal structures are pretty vague. These results are reproduced and explained by a combination of radiation-magnetohydrodynamic, particle-in-cell and Vlasov-Fokker-Planck simulations, where the cross-scale effects of Biermann battery, Nernst advection, resistive diffusion, Righi-Leduc and particularly kinetic Weibel instability are all taken into account. Our findings provide much enlightenment to the role of magnetic field generation in implosion and hohlraum dynamics of laser fusion.

Laser-driven ion acceleration has attracted global interest for its potential towards the development of a new generation of compact, low-cost accelerators. Remarkable advances have been seen in recent years with a substantial proton energy increase in experiments, when nanometer-scale ultrathin foil targets and high-contrast intense lasers are applied. However, the exact acceleration dynamics and particularly the ion energy scaling laws in this novel regime are complex and still unclear. Here, we derive a scaling law for the attainable maximum ion energy from such laser-irradiated nanometer-scale foils based on analytical theory and multidimensional particle-in-cell simulations, and further show that this scaling law can be used to accurately describe experimental data over a large range of laser and target parameters on different facilities. This provides crucial references for parameter design and experimentation of the future laser devices towards various potential applications.

The relativistic spin operator cannot be uniquely defined within relativistic quantum mechanics. Searching for relativistic equations that describe both the evolution of the spin and its influence on the motion of particles with spin represents a problem with almost centenary history. We develop a self-consistent module for modeling relativistic particles with spin motion into three-dimensional particle-in-cell simulations, where the expression of the spin-induced force can be chosen by various semiclassical models, such as the Frenkel and noncovariant Derbenev-Kondratenko models. Through simulations, we propose a potential experimental scheme for observing and testing theoretical descriptions on relativistic spin dynamics, where ultraintense lasers are used to collide with relativistic electron beams. The basis for the scheme is that different models predict different transverse polarization distributions of the scattered electrons after interactions, which can be measured in experiments.

Inverse magnetic energy transfer from small to large scales is a key physical process for the origin of large-scale strong magnetic fields in the universe. However, so far, from the magnetohydrodynamic perspective, the onset of inverse transfer is still not fully understood, especially the underlying dynamics. Here, we use both two-dimensional and three-dimensional particle-in-cell simulations to show the self-consistent dynamics of inverse transfer in collisionless decaying turbulent plasmas. Using the space filtering technique in theory and numerical analyses, we identify magnetic reconnection as the onset and fundamental drive for inverse transfer, where, specifically, the subscale electromotive force driven by magnetic reconnection do work on the large-scale magnetic field, resulting in energy transfer from small to large scales. The mechanism is also verified by the strong correlations in locations and characteristic scales between inverse transfer and magnetic reconnection.

Results from the previous experiment have demonstrated bone loss and excess metabolism in Hyperthyroidism-induced rats. Thus, an underlying relationship between metabolism and bone loss was speculated. In addition, previous studies have shown the influence of acetylation on metabolism in tissues and diseases. The hypothesis from this case study suggests that excessive metabolism is induced by acetylation of vital metabolism enzymes.In the case study, a HYP-induced osteoporosis rat model was used and the glucose metabolite was tested through the acetylation of proteins by the mass spectrometer. The results showed that pivotal enzymes of Glycolysis-Tricarboxylic acid cycle-Oxidative phosphorylation were acetylated along with upregulated metabolites. With all acetyly-lysine sites of related enzymes listed, the results in this study showed that bone loss in HYP rats was accompanied by the upregulation of CREB-binding protein (Crebbp, CBP). Furthermore, it is also indicated that CBP has a close relationship with the enhancement of LDHA which promotes glucose metabolism.Acetylation is highly correlated with excessive energy metabolism in HYP-induced osteoporotic rats, where a representation relationship between CBP and LDHA is demonstrated.Hyperthyroidism may lead to osteoporosis. Our study found an interesting phenomenon of hyperthyroidism induced-osteoporosis is that osteoporosis is accompanied by excessive glucose metabolism. In this process, some molecular mechanisms are still unclear. This study indicates a high degree of acetylation of metabolic enzymes, which may be closely related to excessive glucose metabolism. The relationship between CBP and LDHA was also investigated in this study, which showed that CBP and LDHA had some extent interaction. Glucose metabolism and acetylation maybe all associated with hyperthyroidism induced-osteoporosis. This data provides new insights into the molecular mechanisms of hyperthyroidism induced-osteoporosis.

Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3β (GSK-3β) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1β, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3β pathway and finally leading to cognitive impairment.

Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5 mg conbercept, a new anti-vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients.A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial.Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group.The conbercept group received intravitreal injections of conbercept (0.5 mg) once monthly for the first 3 months, then once quarterly until month 12 (3 + Q3M). The sham group received first 3 monthly sham injections and then 3 monthly injections of conbercept (0.5 mg) followed by quarterly administrations until month 12.The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3.A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were +9.20 letters in the conbercept group and +2.02 letters in the sham group, respectively (P .001). At 12 months, the mean changes from baseline in BCVA letter score were +9.98 letters in the conbercept group and +8.81 letters in the sham group (P = .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure.A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.

The formation and structure of a collisional shock wave in a fully ionized plasma is studied via full particle-in-cell simulations, which allows the complex momentum and energy transfer processes between different charged particles to be treated self-consistently. The kinetic energy of the plasma flow drifting towards a reflecting piston is found to be rapidly converted into thermal motion under the cooperative effects of ion-ion collisions, ion-electron collisions, and electric field charged-particle interactions. The subsequent shock evolution is influenced by the ``precursor'' ion beam before a quasisteady state is reached. The shock wave structure is then analyzed from a two-fluid transport viewpoint, which is found to be affected by ``flux-limiting'' electron transport, the nonthermal ions, and the charge separation electric field.

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

Herein, we reported a case of complete excision of the jejunum for the treatment of esophageal cancer. A 62-year-old male was admitted with complaints of “difficulty in eating for one month and chest pain for 10 days". For complete gastrectomy and colonic polyposis, we chose the jejunum. We completely excised the jejunum and its vessels, anastomosed to the esophageal tumor resection, with no significant complications. This case showed that complete excision of the jejunum with bowel and vessels is an alternative surgical method for the treatment of esophageal cancer with free bowel shortage and no torsion of blood vessels.

A method for the production of intense circularly polarized (CP) attosecond pulses from relativistic laser-solid interactions is proposed, where a two-color linearly polarized (LP) laser is used. The polarization, photon frequency, and other properties of the obtained attosecond pulse can be controlled by adjusting the ratio of the dichromatic driving LP field in different harmonics, which is much easier and more efficient than those previously using CP driving lasers. Both one- and two-dimensional particle-in-cell simulations show that a CP attosecond extreme-ultraviolet pulse with an intensity of $1.4\ifmmode\times\else\texttimes\fi{}{10}^{19}\phantom{\rule{0.16em}{0ex}}\mathrm{W}/{\mathrm{cm}}^{2}$ and a duration of about 120 as is obtained by a two-color LP laser at intensities in the fundamental and second harmonics of, respectively, $1.5\ifmmode\times\else\texttimes\fi{}{10}^{22}$ and $6.4\ifmmode\times\else\texttimes\fi{}{10}^{21}\phantom{\rule{0.16em}{0ex}}\mathrm{W}/{\mathrm{cm}}^{2}$, which can be applied for the detection of the magnetic and chiral properties of materials.

Optica 7(4), 355-358 (2020). doi:10.1364/OPTICA.385147, Published by OSA, Washington, DC

A configuration to identify the stochastic effect of the quantum radiation reaction is proposed, where electrons are put in a standing wave of two colliding ultraintense lasers. By comparing the simulation results of the semiclassical and quantum models, we find that if the semiclassical model is used, a particular trapping of electrons between two electric-field nodes is induced, which, however, does not exist once the correct quantum model is applied. This results in different features of the electron density, energy, and angular distributions, which can be measured in experiments.

Experimental and simulation data [Moreau et al., Plasma Phys. Control. Fusion 62, 014013 (2019); Kaymak et al., Phys. Rev. Lett. 117, 035004 (2016)] indicate that self-generated magnetic fields play an important role in enhancing the flux and energy of relativistic electrons accelerated by ultra-intense laser pulse irradiation with nanostructured arrays. A fully relativistic analytical model for the generation of the magnetic field based on electron magneto-hydrodynamic description is presented here. The analytical model shows that this self-generated magnetic field originates in the nonparallel density gradient and fast electron current at the interfaces of a nanolayered target. A general formula for the self-generated magnetic field is found, which closely agrees with the simulation scaling over the relevant intensity range. The result is beneficial to the experimental designs for the interaction of the laser pulse with the nanostructured arrays to improve laser-to-electron energy coupling and the quality of forward hot electrons.

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Nuclear reactions in the plasma environment can be substantially different from those in conventional laboratory non-plasma cases, which have attracted considerable attention in the fields of fusion and astrophysics. To self-consistently model the nuclear reaction process during plasma dynamic evolution, an extended nuclear reaction calculation module is developed and included in two-dimensional particle-in-cell simulations. Through the self-consistent simulations, we systematically show that, apart from the plasma screening, the kinetic Weibel instability (WI) occurring in plasmas also results in significant enhancement of nuclear reactions, where the self-generated magnetic fields play a key role. Specifically, the self-generated magnetic fields in WI deflect ion motions, decreasing the relative velocity, and convert plasma kinetic energy to thermal energy, increasing the ion temperature. The simulation results show that, for the t ( d , n ) α reaction with a sharp resonance peak in the cross section, the reaction product yield is enhanced four times due to the WI. For nuclear reactions that have more prominent resonance peaks in the cross section, like 12 C ( p , γ ) 13 N , it is expected that such enhancements can reach up to one or several orders of magnitude.

We demonstrate theoretically and numerically that intense isolated circularly polarized (CP) attosecond pulses can be generated from ultrathin foil targets irradiated by two relativistic lasers from opposite sides, where their polarizations are orthogonal to each other. With a proper matching condition, the compressed oscillating plasma mirrors on both sides of the foil are pushed inside by laser radiation pressures, eventually merging together to form a dense electron nanobunch under the effect of orthogonal laser fields. This nanobunch reaches both high density and high energy in only half a laser cycle and smears out in others, resulting in coherent synchrotron emission of a single attosecond pulse with circular polarization. Two-dimensional particle-in-cell simulations show that an intense isolated CP attosecond XUV pulse with an intensity of 1.2 × 1019 W cm−2 and a duration of ∼75 as can be obtained by two lasers with the same intensity of 2.1 × 1020 W cm−2.