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Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the axon and transported back to the soma. This transport is essential since the final degradation of the vesicular content occurs only close to or in the soma. Here, we established an in vivo live-imaging model in the rat optic nerve using viral vector mediated LC3-labeling and two-photon-microscopy to analyze axonal transport of AVs. Under basal conditions in vivo, 50% of the AVs are moving with a majority of 85% being transported in the retrograde direction. Transport velocity is higher in the retrograde than in the anterograde direction. A crush lesion of the optic nerve results in a rapid breakdown of retrograde axonal transport while the anterograde transport stays intact over several hours. Close to the lesion site, the formation of AVs is upregulated within the first 6 h after crush, but the clearance of AVs and the levels of lysosomal markers in the adjacent axon are reduced. Expression of p150Glued, an adaptor protein of dynein, is significantly reduced after crush lesion. In vitro, fusion and colocalization of the lysosomal marker cathepsin D with AVs are reduced after axotomy. Taken together, we present here the first in vivo analysis of axonal AV transport in the mammalian CNS using live-imaging. We find that axotomy leads to severe defects of retrograde motility and a decreased clearance of AVs via the lysosomal system. [ABSTRACT FROM AUTHOR]

In recent years, there is a growing demand for materials that can both improve the mechanical properties of structures and carry out health monitoring and risk warning. In this case, in order to realize distributed deformation monitoring, a new method of making geogrid by 3D printing technology is proposed. The grille rib is made by embedding the conductive polymer (ground carbon fiber as conductive filler) into the insulating shell (PLA material) in the specified path, and then the rib is vertically crossed into each other to form a grille sample. In order to study the distributed deformation monitoring function of this grid, a manual push–pull testing machine was used to conduct a load–unload experiment to analyze the change rule of resistance on the grid plane. The following conclusions were obtained: the closer the ribs are to the load bearing point, the greater the change in resistance, and conversely, the farther the ribs are from the load bearing point, the smaller the change in resistance. Depending on the geogrid network characteristics, the electrical resistance distribution on the geogrid plane can be obtained by superimposing the resistance values of the horizontal and longitudinal ribs, then the location and the magnitude of deformation can be estimated. Additionally, this study carried out numerical simulation of the grid model based on ANSYS 15.0 software and compared with the loading experiment results to verify that the force deformation position can be retrieved through the change of resistance. [ABSTRACT FROM AUTHOR]

Laser deposition manufacturing (LDM) technology provides the potential to manufacture large, difficult-to-process metal components for aerospace and other applications. However, the residual stresses resulting from the considerable temperature gradients in the LDM process can lead to distortion and even cracking of the fabricated components. Rapidly predicting the distortion for large additive metal components is critical to controlling the distortion and achieving high-quality forming of large components. Considering the principle of LDM technology, the partitioning method based on typical geometric features for aerospace titanium alloy frames, beams, and wall plates is proposed in this paper. It establishes a rapid prediction method for distortion of large additive metal components based on feature partitioning and temperature function method (TFM) by considering the effect of critical parameters of temperature function on distortion prediction. The results show that the prediction of additive component distortion through this method agrees with the results predicted by the traditional method and experimental results. Furthermore, the computational efficiency of the method has improved by 96% compared to the traditional approach, meeting the need for rapid distortion prediction in large metal additive components. [ABSTRACT FROM AUTHOR]

• This study evaluated the mechanism underlying how the inhibition of Drp1-mediated mitochondrial fission improves acute kidney injury induced by treatment with contrast agents in vitro and in vivo. • Using a mouse model of contrast-induced acute kidney injury (CI-AKI), we found that Drp1 inhibition reduced the expression of proteins associated with the NLRP3 inflammasome and increased the levels of kidney injury markers. • In vitro , these effects were reversed by Drp1 overexpression. We believe that our study makes a significant contribution to the literature because we have shown that Drp1 inhibition could alleviate the deleterious effects of CI-AKI by regulating mitochondrial fission, reducing mitochondrial reactive oxygen species production, and reducing the interaction between thioredoxin-interacting protein (TXNIP) and the NLRP3 inflammasome complex. Acute kidney injury (AKI) is a critical complication known for their extremely high mortality rate and lack of effective clinical therapy. Disorders in mitochondrial dynamics possess a pivotal role in the occurrence and progression of contrast-induced nephropathy (CIN) by activating NLRP3 inflammasome. The activation of dynamin-related protein-1 (Drp1) can trigger mitochondrial dynamic disorders by regulating excessive mitochondrial fission. However, the precise role of Drp1 during CIN has not been clarified. In vivo experiments revealed that inhibiting Drp1 through Mdivi-1 (one selective inhibitor of Drp1) can significantly decrease the expression of p-Drp1 (Ser616), mitochondrial p-Drp1 (Ser616), mitochondrial Bax, mitochondrial reactive oxygen species (mROS), NLRP3, caspase-1, ASC, TNF-α, IL-1β, interleukin (IL)-18, IL-6, creatinine (Cr), malondialdehyde (MDA), blood urea nitrogen (BUN), and KIM-1. Moreover, Mdivi-1 reduced kidney pathological injury and downregulated the interaction between NLRP3 and thioredoxin-interacting protein (TXNIP), which was accompanied by decreased interactions between TRX and TXNIP. This resulted in increasing superoxide dismutase (SOD) and CAT activity, TRX expression, up-regulating mitochondrial membrane potential, and augmenting ATP contents and p-Drp1 (Ser616) levels in the cytoplasm. However, it did not bring impact on the expression of p-Drp1 (Ser637) and TXNIP. Activating Drp-1though Acetaldehyde abrogated the effects of Mdivi-1. In addition, the results of in vitro studies employing siRNA-Drp1 and plasmid-Drp1 intervention in HK-2 cells treated with iohexol were consistent with the in vivo experiments. Our findings revealed inhibiting Drp1 phosphorylation at Ser616 could ameliorate iohexol –induced acute kidney injury though alleviating the activation of the TXNIP-NLRP3 inflammasome pathway. [ABSTRACT FROM AUTHOR]

• A dual-space compressive sensing method is developed for the collection and reconstruction of 4D-STEM data at high fidelity. • The approach is tested on the subsampled datasets created from a full 4D-STEM dataset of a nanodevice sample, and demonstrated experimentally using random scan in real-space. • The same reconstruction algorithm can be used for compression of 4D-STEM datasets, leading to a large reduction (100 times or more) in data size, while retaining the fine features of 4D-STEM imaging. Four-dimensional Scanning Transmission Electron Microscopy (4D-STEM) is a powerful technique for high-resolution and high-precision materials characterization at multiple length scales, including the characterization of beam-sensitive materials. However, the field of view of 4D-STEM is relatively small, which in absence of live processing is limited by the data size required for storage. Furthermore, the rectilinear scan approach currently employed in 4D-STEM places a resolution- and signal-dependent dose limit for the study of beam sensitive materials. Improving 4D-STEM data and dose efficiency, by keeping the data size manageable while limiting the amount of electron dose, is thus critical for broader applications. Here we introduce a general method for reconstructing 4D-STEM data with subsampling in both real and reciprocal spaces at high fidelity. The approach is first tested on the subsampled datasets created from a full 4D-STEM dataset, and then demonstrated experimentally using random scan in real-space. The same reconstruction algorithm can also be used for compression of 4D-STEM datasets, leading to a large reduction (100 times or more) in data size, while retaining the fine features of 4D-STEM imaging, for crystalline samples. [ABSTRACT FROM AUTHOR]

Molybdenum carbide materials have demonstrated remarkable potential in catalyzing the hydrogen evolution reaction (HER). However, further modulation of their performance through simultaneously engineering the size and surface crystal facets remains challenging. Herein, we report the successful fabrication of N-doped carbon-supported monodisperse Mo 2 C nanoparticles with a size of ∼2.06 nm, exhibiting co-exposed (101)/(102) facets-heterojunction, derived from annealing glycine and ammonium molybdate tetrahydrate. The optimized Mo 2 C/NC-Amt catalyst exhibits a low overpotentials of 128 mV to achieve the current density of 10 mA cm−2 and a small Tafel slope of 72 mV dec−1 under alkaline solution. By changing the molybdate precursor, the phase and crystal facet composition of molybdenum carbide can be effectively tuned, which provides a good platform for studying their structure-activity in HER. The theoretical calculations reveal the synergistic effect of (101)/(102) facets-heterojunction accelerates electron transfer and regulates the d band center of Mo 2 C, reducing the reaction barriers of intermediates in the HER process, thus significantly boosting reaction activity. This work proposes a novel insight into the rational fabrication of efficient HER catalysts through facet engineering toward heterojunction construction under the 2.5 nm region. [Display omitted] • Monodisperse Mo 2 C nanoparticles (∼2.06 nm) on N-doped carbon are synthesized. • The formed surface heterojunction involves (101) and (102) facets of Mo 2 C. • DFT calculations reveal the synergistic mechanisms of the facet heterojunctions. • The optimized catalyst presents distinguished HER performance in 1 M KOH. [ABSTRACT FROM AUTHOR]

The intermittent cutting behavior, performing as periodic contact phase and separation phase between abrasive grit and workpiece, is an important characteristic in the ultrasonic vibration-assisted grinding (UVAG). This study investigated the effect of intermittent cutting behavior on the grinding force in UVAG. At first, a grinding force model was established by determining the quantity of effective grits and the grinding force of a single grit. Then, the influences of ultrasonic vibration phase on the intermittent cutting behavior and grinding force were discussed. Finally, the prediction accuracy of the model was tested through experiments. Results indicated that the intermittent cutting behavior was divided into the contact phase and separation phase. A large unchanged chip thickness of 1.05 μm was generated at the start of contact phase. The quantity of effective grits firstly increased to maximum 232 at the vibration phase of 0.5 π and then gradually decreased to zero when entering the separation phase. The maximum error of the grinding force model was 15%, indicating that the model was of high accuracy for the force prediction in UVAG. [ABSTRACT FROM AUTHOR]

Defect engineering of electrode materials is considered highly effective in regulating their performance, among which oxygen vacancies play a vital role. Thereupon, comprehensively understanding effects of oxygen vacancy in electrochemical processes of transition metal oxides stays hot and controversial, representatively for amorphous tungsten oxide films and their electrochromic (EC) behaviors. Upon long‐term cycling, amorphous tungsten oxide suffers from the universal trapping effect governed by the intrinsic host microstructure and transport kinetics of the inserted ions, implying that manipulating oxygen vacancies could be a potential solution to the ion‐trapping problem. Hence, systematic work is urgent for not only tackling the trapping effect but also understanding the effect of oxygen vacancies on EC behaviors. Herein, the concentration of oxygen vacancies in the amorphous tungsten oxide films is modulated over a wide range. In combination with comprehensive experiments and first‐principles calculations, the presence of oxygen vacancy is detrimental to the EC properties, but it greatly attenuates the trapping effect. Excellent cyclic stability is achieved with a 100% optical modulation rate and charge capacity retention after 5000 cyclic voltammetry cycles. This study elucidates understanding of oxygen vacancy engineering in transition metal oxides, particularly regarding trapping effect passivation. [ABSTRACT FROM AUTHOR]

With the advancement of touch screen technology, the application of touch screens in civil aircraft cockpits has become increasingly popular. However, further analysis and research are required to fully promote its applications. The paper researched the usability of touch screens in aircraft cockpit considering the operation performance and subjective NASA-TLX workload evaluation, conducted experimental research on three touch gestures: click, drag, and zoom. Additionally, a comparative analysis was conducted on the touch performance under different layouts, positions, touch sizes, dragging direction angles, and zoom multiples. The touch performance indicators include operation time, error rate, operation speed, and workload. The experimental results show that the 21 mm size has the minimum operation time and workload, and 18 mm size has the lowest error rate in the clicking tasks. Additionally, the performance and workload of the captain's layout are better than those of the co-pilot's layout, and the performance of the center console position is best. The operation speed of the dragging tasks is faster when performed at position R3 compared to other positions. The dragging moving angles with better operation speed are 80°-190° and 250°-290°. The operation performance and workload of the zooming tasks vary depending on the zoom multiples. As the multiple increases, the operation time and workload also increase. There is no difference in operation performance or workload between zooming in and zooming out. The paper provides experimental support and suggestions based on human operation and subjective NASA-TLX workload evaluation for the application of touch screens in civil aircraft cockpits. [ABSTRACT FROM AUTHOR]

Cancer has evolved into a substantial public health concern as the second-leading cause of mortality globally. Radiotherapy and chemotherapy have been the two most widely used cancer therapies in recent years; however, both have drawbacks. Therefore, the focus has shifted to the creation of herbal medicines, the extraction of active ingredients, replacement therapy, and the adverse effects of these medications. Ginsenoside Rh2, which is extracted from ginseng, has been identified in many cancer cells. The immune system of the body is strengthened by ginsenoside Rh2, which can also cause the proliferation, death, and differentiation of tumor cells through various pathways. For instance, it inhibits the expression of the NF- κ B signaling pathway and induces cell apoptosis, affects the expression levels of mitochondrial apoptosis proteins Bcl-2 and Bax, and cooperates with the PD-1 blockade to reactivate T cells to promote an antitumor immune response. Furthermore, ginsenosides Rh2 has the effect of reversing the toxic effect of chemotherapy drugs on normal cells, reducing myocardial damage, and relieving bone marrow function suppression. For clinical applications, it is mainly used as an adjuvant drug for preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and rescue treatment of advanced cancer. This paper summarizes the pharmacological action and mechanism of ginsenosides Rh2 in all kinds of cancer and looks forward to its future development and application. [ABSTRACT FROM AUTHOR]

• Cuproptosis induces oxidative stress damage, acylation of proteins, and oligomerization of acylated TCA cycle proteins. • Cuproptosis plays a significant role in the development and progression of various kidney diseases, such as acute kidney injury, chronic kidney disease, diabetic nephropathy, kidney transplantation, and kidney stones. • Inducers or inhibitors of cuproptosis promotes or relieve the cuproptosis pathway. Cuproptosis has recently been identified as a novel regulatory mechanism of cell death. It is characterized by the accumulation of copper in mitochondria and its binding to acylated proteins. These characteristics lead to the downregulation of iron-sulfur cluster proteins and protein toxicity stress, ultimately resulting in cell death. Cuproptosis is distinct from other types of cell death, including necrosis, apoptosis, ferroptosis, and pyroptosis. Cu induces oxidative stress damage, protein acylation, and the oligomerization of acylated TCA cycle proteins. These processes lead to the downregulation of iron-sulfur cluster proteins and protein toxicity stress, disrupting cellular Cu homeostasis, and causing cell death. Cuproptosis plays a significant role in the development and progression of various kidney diseases such as acute kidney injury, chronic kidney disease, diabetic nephropathy, kidney transplantation, and kidney stones. On the one hand, inducers of cuproptosis, such as disulfiram (DSF), chloroquinolone, and elesclomol facilitate cuproptosis by promoting cell oxidative stress. In contrast, inhibitors of Cu chelators, such as tetraethylenepentamine and tetrathiomolybdate, relieve these diseases by inhibiting apoptosis. To summarize, cuproptosis plays a significant role in the pathogenesis of kidney disease. This review comprehensively discusses the molecular mechanisms underlying cuproptosis and its significance in kidney diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • 370 biphenyl triazoles was modularly synthesized in microplates via click chemistry. • Biphenyl triazoles 6 and 16 were identified as novel hyaluronidase inhibitors. • Compounds 6 and 16 were characterized as non-competitive inhibitors of hyaluronidase. • Compounds 6 and 16 notably inhibited NO release in LPS-stimulated macrophages. Hyaluronidase is a promising target in drug discovery, given its overexpression in a range of physiological and pathological processes, including tumor migration, skin aging, sagging, and wrinkling, as well as inflammation and bacterial infections. In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6 , as well as quinoline-containing triazoles 15 and 16 , as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulated macrophages. Remarkably, compound 6 significantly reduced NO release by 74 % at a concentration of 20 μM. [ABSTRACT FROM AUTHOR]

Electrochromic (EC) technology is highly desirable in energy-conserving bistable displays as it can dynamically modulate color changes under small voltages and maintain the changed color after the power is cut off. For its practical application, low cost, easy fabrication and good durability are crucial. The shoulder-by-shoulder EC structure is talented in achieving low cost and easy fabrication because the counter electrode and its corresponding conductive layer were not necessary in it. Moreover, the EC material determines the stability against light radiation and long-term use. Herein, crystalline NiO films were selected owing to their gifted structure stability in crystalline state, and were fabricated through the sputtering process at a high deposition rate of 50 nm/min. The NiO film was further optimized to a laminated structure with the room-temperature-deposited NiO at the top and the 100 °C-deposited NiO at the bottom adjacent to ITO substrates as the adhesive layer. A high optical modulation rate of 59 % and excellent cycling stability with only 6 % degradation over 3000 cycles were achieved. Bistable price tags were then designed using the high-performance laminated NiO film and shoulder-by-shoulder EC structure. Thus fabricated EC material will significantly advance the applications of EC technology in various intelligent display scenarios. A low-cost easy-fabrication ultrafast-switching excellent-stability electronic price tag was all-in-one fabricated based on the shoulder-by-shoulder electrochromic structure and high-performance laminated NiO film with striking balance between the color-changing capability and cycling stability. [Display omitted] • Design of structure strikes a balance between the color-changing capability and the cycling stability of NiO films. • The optimized EC performances are originating from the concerted coexisting of crystalline and amorphous components. • Low-cost easy-fabrication ultrafast-switching excellent-stability price tags were developed. [ABSTRACT FROM AUTHOR]