Postoperative cognitive dysfunction (POCD) is a significant concern for the elderly population worldwide. This study explored the effects of esketamine on aged mice with POCD and investigate its ...mechanism of action involving the TLR4/MyD88/MAPK pathway. We administrated esketamine, along with lipopolysaccharide or anisomycin, to the aged POCD mouse models. We assessed their cognitive function using the Morris water maze test. Additionally, we evaluated histopathological changes/neuronal apoptosis in the mouse hippocampal CA1 area through HE/TUNEL stainings. Furthermore, we measured IL‐1β/IL‐6/TNF‐α/TLR4/MyD88/MAPK (p‐p38/p38) levels in mouse hippocampal tissues using ELISA/RT‐qPCR/Western blotting. Lastly, we analyzed the interaction between TLR4 and MyD88 using a co‐immunoprecipitation assay. Our findings showed that esketamine effectively mitigated POCD in aged mice. This was evident from the improved cognitive performance observed in the Morris water maze test, characterized by reduced escape latency/increased number of platform crossing/a higher percentage of time spent in the target quadrant. Furthermore, esketamine exhibited a protective effect against neuronal apoptosis and reduced the levels of inflammatory factors. These findings suggest that esketamine exerts an anti‐inflammatory effect by downregulating TLR4/MyD88, thereby attenuating the inflammatory response associated with POCD. Additionally, esketamine suppressed the p38 MAPK pathway by inhibiting the TLR4/MyD88 signaling cascade. Esketamine demonstrated its efficacy in improving postoperative inflammation and cognitive impairment in aged mice by inhibiting the TLR4/MyD88 pathway. The activation of p38 MAPK signaling diminished the beneficial effects of esketamine in aged POCD mice. Collectively, the underlying mechanism of esketamine in mitigating POCD in aged mice involves the suppression of the TLR4/MyD88/p38 MAPK pathway.
A zirconium-porphyrin metal–organic framework/graphene oxide composite is successfully constructed and employed to fabricate an aptamer-based electrochemical aptasensor with ultra-sensitive detecting ...performance for chloramphenicol.
Display omitted
More and more attentions have been focused on design and synthesis of novel metal-organic framework/graphene oxide (MOF/GO) composites with unique performance. Zirconium-porphyrin MOF (PCN-222) is in-situ synthesis with the existence of GO with −COOH group to artfully fabricate a PCN-222/GO composite. This composite can be employed as functional material to modify the working electrode. Thanks to excellent electrical conductivity of GO, abundant mesoporous channels and numerous Zr(IV) metal sites of PCN-222, this composite can immobilize a large amount of aptamer through strong π-π stacking interaction and high affinity between phosphate group of aptamer and Zr(IV) site of PCN-222 simultaneously. Hence, an ultra-sensitive electrochemical aptasensor based on PCN-222/GO composite can quantificationally detect trace chloramphenicol with limit of detection of 7.04 pg/mL (21.79 pmol/L) from 0.01 ng/mL to 50 ng/mL by electrochemical impedance spectroscopy even in real samples. Meanwhile, this fabricated aptasensor reveals good repeatability, outstanding selectivity and preferable long-term storage. This research provides a useful approach to construct MOF/GO composites for fabricating electrochemical aptasensors in the electrochemical detection field.
Summary of main observation and conclusion
A Pd(II)‐catalyzed enantioselective intramolecular amidation of both benzylic and unbiased methylene C(sp3)−H bonds for the straightforward synthesis of ...chiral β‐lactams from aliphatic carboxamides is reported. The combination of 2‐pyridinylisopropyl (PIP) auxiliary with 3,3’‐substituted BINOL ligands is crucial for the enhancement of both reactivity and enantiocontrol of differentiating unbiased methylene C(sp3)−H bonds. The desired chemoselective C—N reductive elimination was achieved by employing 2‐fluoro‐1‐iodo‐4‐nitrobenzene as oxidant.
Abstract
The combination of a rotary-steerable system (RSS) and power screws has become the main drilling tool for the efficient exploration and development of unconventional oil and gas. However, ...the application of point-the-bit (POB) rotary-steerable tools in directional drilling subjects spindle bearings to continuous alternating stress, which can lead to fatigue failure. In this study, numerical analysis and simulation are employed to guide the engineering application of rotary-steerable tools, particularly in the field of oil and gas exploitation. The structural composition and steering principles of rotary-steerable tools are analyzed. The influence of the structural parameters of the spindle on the deflection capacity of the tool is analyzed, and the optimal structural parameters are selected. Based on the results, the recommended distances between the various components of the tool could be obtained. Moreover, the maximum deflection capacity increases with torque when the WOB (weight-on-bit) is constant. Similarly, at constant torque, the maximum deflection capacity increases with the WOB. Overall, the WOB has a greater influence on the maximum deflection capacity than torque. To ensure the safe operation of the spindle, the WOB and torque must be within 200 kN and 20 kN·m, respectively. The findings of this study provide valuable insights into the safe application of POB rotary-steerable tools.
Ultralow friction can be achieved with 2D materials, particularly graphene and MoS2. The nanotribological properties of these different 2D materials have been measured in previous atomic force ...microscope (AFM) experiments sequentially, precluding immediate and direct comparison of their frictional behavior. Here, friction is characterized at the nanoscale using AFM experiments with the same tip sliding over graphene, MoS2, and a graphene/MoS2 heterostructure in a single measurement, repeated hundreds of times, and also measured with a slowly varying normal force. The same material systems are simulated using molecular dynamics (MD) and analyzed using density functional theory (DFT) calculations. In both experiments and MD simulations, graphene consistently exhibits lower friction than the MoS2 monolayer and the heterostructure. In some cases, friction on the heterostructure is lower than that on the MoS2 monolayer. Quasi-static MD simulations and DFT calculations show that the origin of the friction contrast is the difference in energy barriers for a tip sliding across each of the three surfaces.
Passive cooling, which cools without any electricity input, has had a great impact on global energy consumption. The recent progress on radiative cooling has many potential applications in efficient ...passive cooling. During the day, this strategy uses the maximized infrared emissivity via the atmospheric transparency windows for radiating heat and minimizing solar absorption. However, the realization of daytime radiative coolers with ideal selective mid-infrared emissivity is still a great challenge. Here, we firstly design and numerically demonstrate a near-ideal radiative cooler operating below the ambient temperature, achieving both broadband selective emissivity in the infrared atmospheric window and extremely low absorption in the entire solar spectrum, realizing a net cooling power exceeding 122W/m2 at ambient temperature. The cooling effect can still persist under significant nonradiative heat exchange conditions. The design of multi-layer all-dielectric micropyramid structure in this work not only solves the shortcoming of poor mid-infrared selectivity in planar photonics device, but also overcomes the disadvantage of high solar absorption in metal/dielectric metamaterials. The comparisons of physics mechanism between this multi-layer all-dielectric structure and previously reported multi-layer metal/dielectric structure also are investigated clearly. Thus, this study can help pave the way for designing ideal daytime radiative coolers.
Display omitted
•A near-ideal radiative cooler is demonstrated by designing a metamaterial structure.•The radiative cooler possesses both selective MIR emissivity and low solar absorption.•The high mid-infrared absorption of this structure is attributed to moth-eye effect.•Average MIR emissivity can be maintained above 80% for incident angles less than 70°.
New classes arise frequently in our ever-changing world, e.g., emerging topics in social media and new types of products in e-commerce. A model should recognize new classes and meanwhile maintain ...discriminability over old classes. Under severe circumstances, only limited novel instances are available to incrementally update the model. The task of recognizing few-shot new classes without forgetting old classes is called few-shot class-incremental learning (FSCIL). In this work, we propose a new paradigm for FSCIL based on meta-learning by LearnIng Multi-phase Incremental Tasks ( Limit ), which synthesizes fake FSCIL tasks from the base dataset. The data format of fake tasks is consistent with the 'real' incremental tasks, and we can build a generalizable feature space for the unseen tasks through meta-learning. Besides, Limit also constructs a calibration module based on transformer, which calibrates the old class classifiers and new class prototypes into the same scale and fills in the semantic gap. The calibration module also adaptively contextualizes the instance-specific embedding with a set-to-set function. Limit efficiently adapts to new classes and meanwhile resists forgetting over old classes. Experiments on three benchmark datasets (CIFAR100, mini ImageNet, and CUB200) and large-scale dataset, i.e., ImageNet ILSVRC2012 validate that Limit achieves state-of-the-art performance.
New Findings
What is the central question of this study?
What is the role of the long non‐coding RNA X‐inactive specific transcript (XIST), which is up‐regulated in injured podocytes and membranous ...nephropathy, in the pathogenesis of membranous nephropathy?
What is the main finding and its importance?
XIST was up‐regulated in kidney tissue with membranous nephropathy and in injured podocytes. Down‐regulation of XIST inhibited podocyte apoptosis. XIST negatively regulated miR‐217, and miR‐217 modulated Toll‐like receptor 4. Inhibition of XIST suppressed podocyte apoptosis induced by angiotensin II via miR‐217.
Membranous nephropathy is often characterized by glomerular podocyte injury. Up‐regulation of the long non‐coding RNA (lncRNA) X‐inactive specific transcript (XIST) has been verified in membranous nephropathy and in injured podocytes. Here the role of XIST in podocyte injury and membranous nephropathy was explored. Quantitative real‐time PCR and western blot were performed to detect the expression of XIST and miR‐217, and Toll‐like receptor 4 (TLR4) protein, respectively. Podocyte apoptosis was evaluated with flow cytometry. Interaction between XIST and miR‐217 was analysed by RNA immunoprecipitation and RNA pull‐down assay. A dual luciferase reporter assay was used to examine the interplay between miR‐217 and TLR4. Up‐regulation of the lncRNA XIST and angiotensin II (Ang II) and kidney and podocyte injury were indicated in kidney tissue of patients with membranous nephropathy. Increase of XIST and apoptosis were induced by Ang II in podocytes. Down‐regulation of XIST reversed podocyte apoptosis induced by Ang II. MiR‐217 was negatively regulated by XIST. MiR‐217 controlled TLR4 by targeting its 3′‐untranslated region. XIST modulated TLR4 through miR‐217 and inhibition of XIST reduced podocyte apoptosis induced by Ang II via regulating miR‐217. Down‐regulation of XIST ameliorates podocyte apoptosis via the miR‐217–TLR4 pathway, which may improve membranous nephropathy.
Novel thin film nanocomposite (TFN) membranes were fabricated by interfacial polymerization on imogolite nanotubes (INTs) blended substrates for the forward osmosis (FO) desalination. INTs as ...intrinsically hydrophilic nanotubes were synthesized and characterized to be with length of 100–200nm, outer diameter of 2nm, and inner diameter of 1nm. Then, different INTs loading (0.33, 0.66 and 1.0wt%) were used to prepare INTs blended polysulfone (PSf) substrates, whose morphology and properties were investigated in detail. It is found that the incorporation of INTs obviously enhanced the hydrophilicity, pure water flux, overall porosity, surface porosity and roughness of PSf substrates. The TFN membranes demonstrated superior water permeance and salt rejection compared to the thin film composite (TFC) membranes. Among others, TFN 0.66 with 0.66wt% INTs blended PSf substrate showed the best over-all properties which are important for demonstrating good osmotic performance in FO. Moreover, TFN membranes presented smaller structural parameters than TFC membrane, which means that internal concentration polarization (ICP) effect can be alleviated by incorporating hydrophilic INTs into substrates. The obtained TFN membranes with INTs blended substrates could develop opportunities in desalination.
•Hydrophilic imogolite nanotubes were synthesized and blended in PSf substrate.•Hydrophilicity and porosity of the modified PSf substrates were improved.•Novel thin film nanocomposite FO membranes were developed.•TFN FO membranes exhibited low structural parameter and minimum ICP.
PDF
