The recurrence of biofilm-associated infections (BAIs) remains high after implant-associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel “interference-regulation strategy” based on bovine serum albumin–iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen (1O2)-sensitized mild hyperthermia for combating BAIs is reported. The catalase-like BIONPs convert abundant H2O2 inside the biofilm-microenvironment (BME) to sufficient oxygen gas (O2), which can efficiently enhance the generation of 1O2 under near-infrared irradiation. The 1O2-induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr-A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia-induced bacterial membrane disintegration results in protein leakage and 1O2 penetration to kill bacteria inside the biofilm. Subsequently, BIONPs-induced immunosuppressive microenvironment re-rousing successfully re-polarizes macrophages to pro-inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this 1O2-sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild-hyperthermia, and immunotherapy, providing a novel and effective anti-biofilm strategy. 相似文献
In the field of weakly supervised semantic segmentation (WSSS), Class Activation Maps (CAM) are typically adopted to generate pseudo masks. Yet, we find that the crux of the unsatisfactory pseudo masks is the incomplete CAM. Specifically, as convolutional neural networks tend to be dominated by the specific regions in the high-confidence channels of feature maps during prediction, the extracted CAM contains only parts of the object. To address this issue, we propose the Disturbed CAM (DCAM), a simple yet effective method for WSSS. Following CAM, we adopt a binary cross-entropy (BCE) loss to train a multi-label classification model. Then, we disturb the feature map with retraining to enhance the high-confidence channels. In addition, a softmax cross-entropy (SCE) loss branch is employed to increase the model attention to the target classes. Once converged, we extract DCAM in the same way as in CAM. The evaluation on both PASCAL VOC and MS COCO shows that DCAM not only generates high-quality masks (6.2% and 1.4% higher than the benchmark models), but also enables more accurate activation in object regions. The code is available at https://github.com/gyyang23/DCAM. 相似文献
Despite the merits of high specific capacity, low cost, and high safety, the practical application of aqueous Zn metal batteries (AZMBs) is plagued by the dendritic growth and corrosion reaction of Zn metal anodes. To solve these issues, a Zn3(PO4)2·4H2O protective layer is in-situ constructed on Zn foil (Zn@ZnPO) by a simple hydrothermal method, avoiding the traditional slurry-casting process. The insulating and conformable ZnPO layer improves the wettability of Zn@ZnPO and aqueous electrolyte via decreasing the contact angle to 11.7o. Compared with bare Zn, the Zn@ZnPO possesses a lower desolvation activation energy of 35.25 kJ mol-1, indicating that the ZnPO fasters the desolvation of hydrated Zn2+ ions and thereby ameliorates their transport dynamics. Micro-morphology and structural characterization show that there are no dendrites forming on the post-cycling Zn@ZnPO anodes, and the interfacial ZnPO layer remains almost identical before and after cycles. It can be explained that the electrochemically stable ZnPO layer acts as an ionic modulator to enable the homogeneous distribution of Zn2+ ions, inhibiting the growth of Zn dendrites. Benefiting from these advantages, the Zn@ZnPO based symmetric and full cells deliver highly reversible Zn plating/stripping behavior and long cycling lifespans. 相似文献
Alzheimer’s Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well. Microglia are CNS-resident immune cells belonging to the myeloid lineage of the innate arm of immunity. Under physiological conditions, microglia are in constant motion in order to carry on their housekeeping function, and they maintain an anti-inflammatory, quiescent state, with low expression of cytokines and no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, aggregates and pathogens), microglia acquire a phagocytic function and overexpress cytokine gene modules. This process is generally regarded as microglia activation and implies that the production of pro-inflammatory cytokines is counterbalanced by the synthesis and the release of anti-inflammatory molecules. This mechanism avoids excessive inflammatory response and inappropriate microglial activation, which causes tissue damage and brain homeostasis impairment. Once the pathogenic stimulus has been cleared, activated microglia return to the naïve, anti-inflammatory state. Upon repeated stimuli (as in the case of Aβ deposition in the early stage of AD), activated microglia shift toward a less protective, neurotoxic phenotype, known as “primed” microglia. The main characteristic of primed microglia is their lower capability to turn back toward the naïve, anti-inflammatory state, which makes these cells prone to chronic activation and favours chronic inflammation in the brain. Primed microglia have impaired defence capacity against injury and detrimental effects on the brain microenvironment. Additionally, priming has been associated with AD onset and progression and can represent a promising target for AD treatment strategies. Many factors (genetics, environmental factors, baseline inflammatory status of microglia, ageing) generate an aberrantly activated phenotype that undergoes priming easier and earlier than normally activated microglia do. Novel, promising targets for therapeutic strategies for AD have been sought in the field of microglia activation and, importantly, among those factors influencing the baseline status of these cells. The CX3CL1 pathway could be a valuable target treatment approach in AD, although preliminary findings from the studies in this field are controversial. The current review aims to summarize state of the art on the role of microglia dysfunction in AD pathogenesis and proposes biochemical pathways with possible targets for AD treatment. 相似文献
We conduct nanoindentation to investigate dislocation nucleation in SrTiO3 (STO) single crystals with surface orientations of (0 0 1), (0 1 1), and (1 1 1) with loading/unloading rates of 25, 250, and 2500 μN/s. Results reveal that the critical loads (Pc) at which “pop-in” event occurs depend strongly on surface orientations, but slightly related to loading rate. Based on Pc, the critical shear stress that triggers dislocation nucleation was determined by extracting the maximum resolved shear stress (τmax) along the slip systems of STO using the Hertzian solution. The dislocation activation shear stress (τa) was determined by averaging τmax. The determined τa is 9.0–12.0 GPa, close to the shear strength (∼G/2π) of STO, indicating that homogeneous dislocation nucleation dominates the pop-in events. The consistency of the determined τa demonstrates that the frameworks for nanoindentation pop-in analysis established for metals can be extended to ceramics, whereas the influence of the limited slip systems should be taken into consideration. Additionally, we estimated the activation volume and the activation energy via the statistical model proposed by Schuh et al. The small values of the determined activation volume (0.6–9.8 Å3) and the activation energy (0.13–0.70 eV) indicate that the dislocation nucleation possibly begins from a single-atom migration and local point defects may participate in the dislocation nucleation process. That is, heterogeneous nucleation may exist initially but the homogeneous dislocation nucleation dominates the pop-in events. 相似文献
Understanding the recrystallization behavior of cold-rolled silicon steel during continuous heating is essential for optimizing continuous annealing parameters and accurately controlling material performance. To address the limitations of isothermal annealing studies in interpreting actual continuous annealing processes, this study investigates the recrystallization kinetics of Fe–2.3 wt%Si steel using a continuous heating three-point bending method. The method effectively determines the characteristic recrystallization temperatures. Interestingly, these recrystallization characteristic temperatures remain unaffected by the initial load but shift toward higher temperatures with increasing heating rates in the range of 5–15 °C min−1. The average activation energy of recrystallization is estimated to be 144.5 kJ mol−1, comparable to the value of 147.0 kJ mol−1 obtained from the isothermal process through microhardness measurement. The recrystallization kinetics, described by an extended version of the Ozawa–Flynn–Wall model, exhibits excellent agreement with experimental evaluations. By combining the present processing technologies with continuous heating recrystallization kinetics, different recrystallization temperatures and times can be determined, offering valuable insights for optimizing annealing processes. 相似文献
In this study, a defective biochar with honeycomb-like porous structure (BC-PH) was successfully prepared by the activation of pristine biochar derived from bamboo shoot shell with the chemical reagent KOH, and was applied to selectively separate ReO4− (a chemical analogue for radioactive TcO4−) from acidic solutions. 相似文献
In this study, we analyzed the characteristics of heat transfer in non-Newtonian ferrofluids produced by stretchable sheet. Further, we investigated in this study the effects of Arrhenius activation energy and magnetic dipole. We use in this study, a similarity ansatz to simplify the governing system into a nonlinear coupled ordinary differential equations system. We determined the computational solution of the resulting ordinary differential system by applying method with Runge–Kutta method. The influence of beneficial physical parameters on momentum, energy, and concentration profile are shown through graphs. The major finding of this study, the variation of velocity field is reduces for the higher values of , , and . The temperature field increases for higher values of , and reduce for . Further, we conclude in this study the arising or reducing in the concentration, temperature, and velocity field for various physical parameters. The impacts of physical quantities namely skin fraction, Nusselt, and Sherwood numbers are examined through numerically via tables. 相似文献
Activating and masking enzymatic activity on demand is of the highest importance in nature. It is achieved by chemical interconversion of enzymes and the corresponding zymogens through, for example, proteolytic processing or reversible phosphorylation, and affords on-demand activation of enzymes, controlled in space and/or time. In stark contrast, examples of chemical zymogens are very few, and in most cases these are based on disulfide chemistry, which is largely indiscriminate as to the nature of the activating thiol. In this work, we address an outstanding challenge of specificity of reactivation of chemical zymogens. We achieve this through engineering affinity between the chemical zymogen and the activator. Additional, higher-level control over zymogen reactivation is installed in a nature-mimicking approach using steroidal hormones. Taken together, the results of this study take a step towards establishing the specificity of reactivation of synthetic, chemical zymogens. We anticipate that the results of this study will contribute significantly to the development of chemical zymogens as tools for diverse use in chemical biology and biotechnology. 相似文献
We developed a cost-effective cobalt-catalyzed electrochemical annulation to generate diversified novel complex dihydroisoquinolin derivatives from amides and alkenes in a simple and maneuverable undivided cell. The reaction proceeded C−H/N−H activation, and the catalyst was regenerated by anodic oxidation. Notably, the strategy of electrocatalysis avoided the consumption of stoichiometric chemical oxidants.
