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Heterogeneity of the tumor microenvironment (TME) is primarily responsible for ineffective tumor treatment and uncontrolled tumor progression. Pyroptosis-based immunogenic cell death (ICD) therapy is an ideal strategy to overcome TME heterogeneity and obtain a satisfactory antitumor effect. However, the efficiency of current pyroptosis therapeutics, which mainly depends on a single endogenous or exogenous stimulus, is limited by the intrinsic pathological features of malignant cells. Thus, it is necessary to develop a synergistic strategy with a high tumor specificity and modulability. Herein, a synergistic nanoplatform is constructed by combining a neutrophil camouflaging shell and a self-synergistic reactive oxygen species (ROS) supplier-loaded polymer. The covered neutrophil membranes endow the nanoplatform with stealthy properties and facilitate sufficient tumor accumulation. Under laser irradiation, the photosensitizer (indocyanine green) exogenously triggers ROS generation and converts the laser irradiation into heat to upregulate NAD(P)H:quinone oxidoreductase 1, which further catalyzes β-Lapachone to self-produce sufficient endogenous ROS, resulting in amplified ICD outcomes. The results confirm that the continuously amplified ROS production not only eliminates the primary tumor but also concurrently enhances gasdermin E-mediated pyroptosis, initiates an ICD cascade, re-educates the heterogeneous TME, and promotes a systemic immune response to suppress distant tumors. Overall, this self-synergistic nanoplatform provides an efficient and durable method for redesigning the immune system for targeted tumor inhibition.

The automotive industry’s trend towards lightweighting has led to a widespread usage of high-strength steels (HSS), which poses challenges for resistance spot welding (RSW) process in auto body manufacturing. One such challenge is the frequent occurrence of the initial gap (IG), which can negatively impact the consistency of the RSW process for HSS. This study aims to reveal this impact by comparing multi-sensor process signals, weld surface morphology, nugget size, and its growth process under standard and two-sided IG conditions. A comprehensive analysis of energy input and contact status is performed to investigate the influence mechanism of IG condition on nugget growth and process signal evolution. The study found that the IG disturbance reduces the initial contact area of the sheet-to-sheet interface in comparison to the standard condition. This results in a faster rise in the sheet temperature, an earlier peak in the resistance signal, and a greater susceptibility to expulsion at the early stage of the welding process. During the subsequent process, there is a significant increase in the contact area of both sheet-to-sheet and electrode-to-sheet interfaces, leading to a decrease in dynamic resistance signal and heat generation. Consequently, the nugget size and electrode displacement signal are smaller than the standard ones. Furthermore, the larger contact area along the gap constraint direction causes more heat generation, ultimately resulting in a larger nugget dimension and indentation size in this particular direction. This research can provide guidance for online monitoring and control for the RSW process of HSS.

Patterning antidots, which are regions of potential hills that repel electrons, into well-defined antidot lattices creates fascinating artificial periodic structures, leading to anomalous transport properties and exotic quantum phenomena in two-dimensional systems. Although nanolithography has brought conventional antidots from the semiclassical regime to the quantum regime, achieving precise control over the size of each antidot and its spatial period at the atomic scale has remained challenging. However, attaining such control opens the door to a new paradigm, enabling the creation of quantum antidots with discrete quantum hole states, which, in turn, offer a fertile platform to explore novel quantum phenomena and hot electron dynamics in previously inaccessible regimes. Here we report an atomically precise bottom-up fabrication of a series of atomic-scale quantum antidots through a thermal-induced assembly of a chalcogenide single vacancy in PtTe2. Such quantum antidots consist of highly ordered single-vacancy lattices, spaced by a single Te atom, reaching the ultimate downscaling limit of antidot lattices. Increasing the number of single vacancies in quantum antidots strengthens the cumulative repulsive potential and consequently enhances the collective interference of multiple-pocket scattered quasiparticles inside quantum antidots, creating multilevel quantum hole states with a tunable gap from the telecom to far-infrared regime. Moreover, precisely engineered quantum hole states of quantum antidots are geometry protected and thus survive on oxygen substitutional doping. Therefore, single-vacancy-assembled quantum antidots exhibit unprecedented robustness and property tunability, positioning them as highly promising candidates for advancing quantum information and photocatalysis technologies.

Background: The musk glands of adult male Chinese forest musk deer (Moschus berezovskiiFlerov, 1929) (FMD), which are considered as special skin glands, secrete a mixture of sebum, lipids, and proteins into the musk pod. Together, these components form musk, which plays an important role in attracting females during the breeding season. However, the relationship between the musk glands and skin of Chinese FMD remains undiscovered. Here, the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing (RNA-seq), and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin. Methods: A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted. Then, based on the anatomical structure of the musk gland, skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD. These tissues were used for RNA-seq, hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Results: Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod, while juvenile FMD did not have any well-developed musk pods. Transcriptomic data revealed that 88.24% of genes were co-expressed in the skin and musk gland tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis found that the genes co-expressed in the abdomen skin, back skin, and musk gland were enriched in biological development, endocrine system, lipid metabolism, and other pathways. Gene Ontology (GO) enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division. Moreover, the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific. qRT-PCR and WB revealed that sex-determining region Y-box protein 9 (Sox9), Caveolin-1 (Cav-1), and androgen receptor (AR) were expressed in all three tissues, although the expression levels differed among the tissues. According to the IHC results, Sox9 and AR were expressed in the nuclei of sebaceous gland, hair follicle, and musk gland cells, whereas Cav-1 was expressed in the cell membrane. Conclusions: The musk gland of Chinese FMD may be a derivative of skin tissue, and Sox9, Cav-1, and AR may play significant roles in musk gland development.

Positioning and tracking technologies have emerged as one of the key techniques for advancing the development of computer-aided medicine. To provide precise medical care, it is necessary to rely on high-precision magnetic positioning functions in medical application scenarios, such as capsule endoscopy and rehabilitation training detection. Due to the position and angle deflection of the magnetic sensor array during manufacturing and installation, there is a deviation between the measured magnetic field intensity of the sensor and the actual magnetic field intensity of the theoretical magnetic source. In this study, a calibration of coordinate measurement method was proposed and an optical plate calibration platform of $300\times450$ mm was developed. The 3-D coordinates of both the bottom surface of the magnetic source placement platforms and the three-axis magnetic sensors were measured with an optical image measuring instrument (NVC500) and a coordinate measuring machine (Daisy8106). The new method for sensor array calibration proposed in this study can be achieved by simply obtaining the sensor deflection angle and the sensor compensation coefficient. Without having to calibrate the sensor position, this method can obtain precise sensor position coordinates and the position and orientation of the calibration magnetic source. Finally, experiments were conducted to determine the association between magnetic source distribution and positioning accuracy, and the results could serve as a guide for the use of magnetic sensor array positioning.

Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase‐3 to lyse gasdermin E (GSDME), and this process can be used as an effective therapeutic strategy. Thus, a selective and powerful inducer of activated caspase‐3 plays a vital role in pyroptosis‐based cancer therapy. Herein, a human cell membrane vesicle‐based nanoplatform (HCNP) is designed for photodynamic therapy (PDT). HCNP is modified with vesicular stomatitis virus G‐protein (VSVG) to anchor nano‐photosensitizers on the tumor cell membrane. Photosensitizers are bonded to HCNP by clicking chemical reaction as pyroptosis inducers. The results show that HCNP effectively disrupts the mitochondrial function of cells by generating reactive oxygen species (ROS) upon laser irradiation; concomitantly, GSDME is cleaved by activated caspase‐3 and promotes pyroptosis of lung cancer cells. Here an effective intervention strategy is proposed to induce pyroptosis based on light‐activated PDT. A human cell membrane vesicle‐based nanoplatform (HCNP) for photodynamic therapy (PDT) is designed, modified with vesicular stomatitis virus G‐protein (VSVG) to anchor nano‐photosensitizers on tumor cell membranes. Upon laser irradiation, HCNP generates reactive oxygen species (ROS), disrupting mitochondrial function and cleaving gasdermin E (GSDME) via caspase‐3, inducing pyroptosis in lung cancer cells. This study presents a light‐activated PDT strategy.

Application of the intelligent on–off valve reduces heat loss. As the critical control component of the intelligent on–off valve, the health state of the brush DC motor directly impacts whether the intelligent on–off valve can perform the regular operation. Therefore, the reliability evaluation of the brush DC motor is of great significance to the whole heat supply network. In this study, the failure mechanism of the brush DC motor is analyzed, and the absolute value of steady-state current variation is taken as the performance degradation characteristic parameter. According to the performance degradation characteristic parameter, the performance degradation model based on the Wiener process is established, and the inverse power rate acceleration model is introduced into the Wiener process to derive the reliability function of the motor. Based on the actual operating conditions that the motor in the intelligent on–off valve needs to start and stop frequently, an accelerated life test based on start-stop is designed. The error analysis result shows that the error between the expected start-stop times predicted by the proposed and the actual average failure start-stop times is only 2.14%. The proposed degradation model is more accurate than the motor's traditional performance degradation model.

ABSTRACTThis study aims to probe the biological functions of long non-coding RNA small nucleolar RNA host gene 18 (SNHG18) on glioma cells and its underlying mechanism. In this study, SNHG18 expression in glioma tissues was quantified employing GEPIA database; quantitative real-time PCR was adopted to examine the expressions of SNHG18, microRNA-338-5p (miR-338-5p) and forkhead box D1 (FOXD1) mRNA in glioma tissues and cell lines; cell proliferation, migration and invasion were detected utilizing cell counting kit-8, EdU and Transwell assays; Western blot was utilized to quantify the protein expressions of E-cadherin, N-cadherin, Vimentin and FOXD1; dual-luciferase reporter gene and RNA immunoprecipitation experiments were utilized to validate the targeting relationships between SNHG18 and miR-338-5p, as well as miR-338-5p and FOXD1 mRNA 3ʹUTR; dual-luciferase reporter gene and chromatin immunoprecipitation assays were utilized to verify the binding of E2F transcription factor 1 (E2F1) to the SNHG18 promoter region. It was revealed that, SNHG18 expression in glioma was up-regulated and associated with unfavorable prognosis of the patients; knockdown of SNHG18 repressed the malignant biological behaviors of glioma cells, enhanced E-cadherin expression and repressed N-cadherin and Vimentin expressions. MiR-338-5p was a target of SNHG18, and SNHG18 promoted the expression of FOXD1 by decoying miR-338-5p. Additionally, E2F1 could bind to the promoter of SNHG18 to elevate its expression. In conclusion, SNHG18 accelerates glioma progression via regulating the miR-338-5p/FOXD1 axis.

In this work, double cantilever beam specimens were used to investigate the rate-dependent fracture of a silicon/epoxy interface. Fracture experiments were conducted at 5 different separation rates, ranging from 0.042 to 8.5 mm/s. For each separation rate, the interfacial properties were extracted by a beam on elastic foundation model and an iterative method, assuming a bilinear traction-separation relation. Rate dependence is observed for the silicon/epoxy interface as both the interfacial toughness and strength increased with the separation rates, which is opposite to the rate dependent fracture behavior of the bulk epoxy in its glassy state. Motivated by this observation, a rate-dependent cohesive zone model is proposed based on a thermally activated bond rupture mechanism. This model relates the interfacial fracture to the breakage of molecular bonds at the interface, and the rate effect develops naturally from the kinetics of damage evolution via the statistical concept of bond survival probability. The double cantilever beam problem with the interfacial bond rupture kinetics was then solved numerically, and the model parameters were extracted by fitting the numerical results to the experimental data. Ideally, this model should be able to explain and predict the rate-dependent fracture of a specific interface (e.g., silicon/epoxy interface) with four parameters, including the bond energy, the critical stress, the initial stiffness and a time scale. However, in order to fit the experimental data, the critical stress had to be adjusted in the present study. Nevertheless, this mechanism-based cohesive zone model offers a promising approach for modeling the rate-dependent fracture, which may also incorporate other mechanisms in future studies. [ABSTRACT FROM AUTHOR]

Immunotherapy is considered to be an effective treatment for cancer and has drawn extensive interest. Nevertheless, the insufficient antigenicity and immunosuppressive tumor microenvironment often cause unsatisfactory therapeutic efficacy. Herein, a photo‐activated reactive oxygen species (ROS) amplifying system (defined as “M‐Cu‐T”) is developed to induce antitumor immune response by triggering a tumor‐specific immunogenic pyroptosis. In M‐Cu‐T, M1 macrophage membrane‐based vesicles are used for drug loading and tumor targeting, photosensitizers (meso‐tetra(4‐aminophenyl) porphyrin, TAPP) are used as a pyroptosis inducer, copper ions (Cu2+) can enhance ROS‐induced pyroptosis by consuming antioxidant systems in cells. As expected, the prepared M‐Cu‐T targets enrichment into tumor cells and cascades the generation of ROS, which further induces pyroptosis through caspase 3‐mediated gasdermin E (GSDME) cleavage under laser activation. The pyroptotic cancer cells accompanying secrete related pattern molecules, induce immunogenic cell death, and activate antitumor immunity for immunotherapy. An effective tumor ablation is observed in LLC and CT26 cancer mouse models. This study provides inspiration for boosting the immunogenicity and achieving satisfactory therapeutic effects in cancer therapy. A photoactivated reactive oxygen species (ROS) amplifying system (defined as “M‐Cu‐T”) is constructed to effectively induce antitumor immune response by triggering a tumor‐specific immunogenic pyroptosis. The pyroptotic cancer cells accompanying secrete related pattern molecules, induce immunogenic cell death, and activate anti‐tumor immunity for immunotherapy. An effective tumor ablation is observed in a cancer mouse model.

Partially premixed combustion (PPC) is a hybrid combustion of Homogeneous Charge Compression Ignition (HCCI) and Diesel Combustion (DC), which has a great potential in reducing the fuel consumption. PPC has a longer premixed time than DC but lesser than HCCI. Therefore it is more stratified than HCCI. This paper first presents results on how the stratification using multiple injections and different EGR influence the efficiency and proposes a control framework for PPC stratification control inspired from the experiments. The control framework is validated in transient operations. Results in both steady and transient operations demonstrated that the more stratified PPC with multiple injections has a lower fuel consumption.

Gasoline-fueled Partially Premixed Combustion is an advanced combustion concept approaching high efficiency as well as low emissions. The most challenging task on controlling a gasoline PPC engine is to regulate the maximum pressure rise rate to reduce engine noise and durability problem. A trade-off relationship between pressure rise rate and soot emissions is observed as a function of pilot injection event. In this paper, a control-oriented model is developed to predict in-cylinder pressure and engine outputs through fuel injection events. Thereafter, two controllers structured with PI and MPC are designed and evaluated separately. Simulation results show that, both controllers satisfy the objective of achieving desired engine load and combustion phasing, with the constraints of pressure rise rate and soot emissions simultaneously. MPC controller produces a smoother transient move with less overshoot, comparing with PI controller with a fast response.

Metabolic reprogramming is a significant feature of tumor cells, and targeting metabolic pathways has become a viable strategy for cancer therapy. Gluconeogenesis is essential to glucose metabolism, with phosphoenolpyruvate carboxykinase 1 (PCK1) and phosphoenolpyruvate carboxykinase 2 (PCK2) as key enzymes. The roles of PCK1 and PCK2 in various cancers remain unclear.

A compact multi-functional, fully variable valve actuation system for six-cylinder engines was proposed. The system can run in both the drive mode and the brake mode of internal-combustion engines. With the help of a distributor, fully variable valve events were achieved with two oil-supply sets, two solenoid valves and one drain valve. The operational parameters of the valve can be adjusted independently for individual cylinders. A numerical study on the controllability of the system was carried out with AVL Hydsim. The calculation results revealed that the timing of the valve opening, the maximum lift, the duration and the time–area value can be adjusted independently or synchronously by controlling the solenoid valves and/or the drain valve. Further correlation analysis results revealed that all the operational parameters of the valve had approximately linear relationships with the corresponding control parameters, and all the correlation coefficients were larger than 0.95, indicating good controllability of the system.

Rate-dependent fracture has been observed for a silicon/epoxy interface as well as other polymer interfaces, where both the interfacial strength and toughness increase with the separation rate. Motivated by this observation, we propose a multiscale approach to modeling a polymer interface, from atomic bonds to the macroscopic specimen, considering the energetics of bond stretching, the entropic effect of long molecular chains, the kinetics of thermally activated chain scission, and statistical distributions of the chain lengths. These multiscale features are seamlessly assembled to formulate a rate-dependent cohesive zone model, which is then implemented within a standard finite element package for numerical simulations. This model relates the macroscopically measurable interfacial properties (toughness, strength, and traction-separation relations) to molecular structures of the interface, and the rate dependence results naturally from the kinetics of damage evolution as a thermally activated process. The finite element simulations with the cohesive zone model are directly compared to double cantilever beam experiments for the rate-dependent fracture of a silicon/epoxy interface, yielding reasonable agreement with just a few parameters for the molecular structures of the interface. Such a multiscale, mechanism-based cohesive zone model offers a promising approach for modeling and understanding the rate-dependent fracture of polymer interfaces. [ABSTRACT FROM AUTHOR]