Search

Abstract Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis.

With the escalating prevalence of global heat waves, heat stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms of liver injury, heat stroke-induced damage is characterized by heat cytotoxicity and heightened inflammation, directly contributing to elevated mortality rates. While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction, their specific correlation with heat stroke liver injury remains unclear. Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke, initiating IL-1β-mediated inflammation. Using single-cell RNA sequencing of murine macrophages, a distinct and highly susceptible Kupffer cell subtype, Clec4F+/CD206+, emerged, with heme oxygenase 1 (HMOX-1) playing a pivotal role. Mechanistically, heat-induced HMOX-1, regulated by early growth response factor 1, mediated ferroptosis in Kupffer cells, specifically in the Clec4F+/CD206+ subtype (KC2), activating phosphatidylinositol 4-kinase beta and promoting PI4P production. This cascade triggered NLRP3 inflammasome activation and maturation of IL-1β. These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells, particularly in Clec4F+/CD206+ KCs. Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke, offering a promising avenue for future therapeutic interventions.

Abstract Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

As an emerging joint learning model, federated learning is a promising way to combine model parameters of different users for training and inference without collecting users’ original data. However, a practical and efficient solution has not been established in previous work due to the absence of efficient matrix computation and cryptography schemes in the privacy-preserving federated learning model, especially in partially homomorphic cryptosystems. In this paper, we propose a Practical and Efficient Privacy-preserving Federated Learning (PEPFL) framework. First, we present a lifted distributed ElGamal cryptosystem for federated learning, which can solve the multi-key problem in federated learning. Secondly, we develop a Practical Partially Single Instruction Multiple Data (PSIMD) parallelism scheme that can encode a plaintext matrix into single plaintext for encryption, improving the encryption efficiency and reducing the communication cost in partially homomorphic cryptosystem. In addition, based on the Convolutional Neural Network (CNN) and the designed cryptosystem, a novel privacy-preserving federated learning framework is designed by using Momentum Gradient Descent (MGD). Finally, we evaluate the security and performance of PEPFL. The experiment results demonstrate that the scheme is practicable, effective, and secure with low communication and computation costs.

Abstract The success of macrophage-based adoptive cell therapy is largely constrained by poor polarization from alternatively activated (M2-like) to classically activated (M1-like) phenotype in the immunosuppressive tumor microenvironment (TME). Here, we show that the engineered macrophage (eMac) with a heat-inducible genetic switch can induce both self-polarization of adoptively transferred eMac and re-polarization of tumour-associated macrophages in response to mild temperature elevation in a mouse model. The locoregional production of proinflammatory cytokines by eMac in the TME dose not only induces the strong polarization of macrophages into a classically activated phenotype, but also ensures that the side effects typical for systemically administrate proinflammatory cytokines are avoided. We also present a wearable warming device which is adaptable for human patients and can be remotely controlled by a smartphone. In summary, our work represents a safe and efficient adoptive transfer immunotherapy method with potential for human translation.

Soil salinization is one of the major factors limiting agricultural production. Utilizing beneficial microorganisms like Piriformospora indica (P. indica) to enhance plant tolerance to abiotic stresses is a highly effective method, but the influence of P. indica on the growth of soybean in natural saline-alkaline soil remains unclear. Therefore, we investigated the effects of non-inoculation, P. indica inoculation, and fertilization on the growth, antioxidant defense, osmotic adjustment, and photosynthetic gas exchange parameters of soybean under two different levels of saline-alkaline stress in non-sterilized natural saline-alkaline soil. The study found that: 1) P. indica inoculation significantly promoted soybean growth, increasing plant height, root length, and biomass. Under mildly saline-alkaline stress, the increases were 11.5%, 16.0%, and 14.8%, respectively, compared to non-inoculated treatment. Under higher stress, P. indica inoculation achieved the same level of biomass increase as fertilization, while fertilization only significantly improved stem diameter. 2) Under saline-alkaline stress, P. indica inoculation significantly increased antioxidant enzyme activities and reduced malondialdehyde (MDA) content. Under mildly stress, MDA content was reduced by 47.1% and 43.3% compared to non-inoculated and fertilized treatments, respectively. Under moderate stress, the MDA content in the inoculated group was reduced by 29.9% and 36.6% compared to non-inoculated and fertilized treatments, respectively. Fertilization only had a positive effect on peroxidase (POD) activity. 3) P. indica inoculation induced plants to produce more osmotic adjustment substances. Under mildly stress, proline, soluble sugars, and soluble proteins were increased by 345.7%, 104.4%, and 6.9%, respectively, compared to non-inoculated treatment. Under higher stress, the increases were 75.4%, 179.7%, and 12.6%, respectively. Fertilization had no significant positive effect on proline content. 4) With increasing stress, soybean photosynthetic capacity in the P. indica-inoculated treatment was significantly higher than in the non-inoculated treatment, with net photosynthetic rate increased by 14.8% and 37.0% under different stress levels. These results indicate that P. indica can enhance soybean’s adaptive ability to saline-alkaline stress by regulating ROS scavenging capacity, osmotic adjustment substance content, and photosynthetic capacity, thereby promoting plant growth. This suggests that P. indica has great potential in improving soybean productivity in natural saline-alkaline soils.

Objectives Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP.Methods We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model.Results A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I2=0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I2=0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia.Conclusions The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360.

Plant wax ester synthase catalyzes the synthesis of wax esters from long-chain alcohols and fatty acids, and plays very important roles in plant wax synthesis and some resistances to drought, pathogenic bacteria, ultraviolet radiation, cold and insect invasion and other environmental stresses; cadmium (Cd) is one of the toxic heavy metals with the highest content in environment, and seriously threatens plant growth, development, quality, yield, and plant food safety. In order to explore the Cd stress expressions of wax ester synthase genes in Rehmannia glutinosa, we identified its wax ester synthase genes from its full-length transcriptome sequencing data, analyzed both physiochemical properties, phytogenetic trees and conserved domains with bioinformatics methods, and tissue expressions and Cd stress expressions using qRT-PCR. The results were as follows: (1) Two wax ester synthase genes, named as RgOATWSD1 and RgOATWSD2, were identified, whose coding proteins were unstable hydrophobic proteins with amino acid lengths of 463 aa and 473 aa, isoelectric points of 8.86 and 9.34 and molecular weights of 51.31 kD and 52.49 kD, respectively. (2) Both proteins contained a conserved acyl_WS_DGAT domain and DUF1298 superfamily, in which the former accounted for 92.65% to 94.50% of the amino acid sequence. (3) Both proteins were located in the endoplasmic reticulum and both secondary structures were mainly composed of random coil and α-helix;RgOATWSD2 was not transmembrane protein but RgOATWSD1. (4) Both were differentially expressed in the roots, stems and leaves of R. glutinosa plants. (5) Both expressions were highly responsive to Cd stress, but both expression change trends were different under Cd stress. This study identifies two wax ester synthase genes in response to Cd stress, and lays a foundation for further research on Cd stress expression and other functions of RgOATWSD.

Abstract Spintronics in halide perovskites has drawn significant attention in recent years, due to their highly tunable spin-orbit fields and intriguing interplay with lattice symmetry. Here, we perform first-principles calculations to determine the spin relaxation time (T 1) and ensemble spin dephasing time ( $${T}_{2}^{*}$$ T 2 * ) in a prototype halide perovskite, CsPbBr3. To accurately capture spin dephasing in external magnetic fields we determine the Landé g-factor from first principles and take it into account in our calculations. These allow us to predict intrinsic spin lifetimes as an upper bound for experiments, identify the dominant spin relaxation pathways, and evaluate the dependence on temperature, external fields, carrier density, and impurities. We find that the Fröhlich interaction that dominates carrier relaxation contributes negligibly to spin relaxation, consistent with the spin-conserving nature of this interaction. Our theoretical approach may lead to new strategies to optimize spin and carrier transport properties.

Objective To investigate the protective effect and possible mechanism of type Ⅱ alveolar epithelial cells (AEC-Ⅱ)-derived exosomal (Exos)-miR-21-5p (miR-21) on the regulation of epithelial sodium channels (ENaC) in hyperoxia-induced acute lung injury (HALI). Methods Sixty male C57BL/6J mice (6-8 weeks old) were subjected, and 20 of them were used to isolate AEC-Ⅱ using differential wall centrifugation, which were further cultured extract derived exosomes with density gradient centrifugation. Transmission electron microscopy was employed to identify the morphology of obtained exosomes. The 40 remaining mice were randomly divided into (n=10): normoxia (Control), hyperoxia (HALI), hyperoxia+Exo-miR-21 (HALI+miR-21), and hyperoxia+siPI3K+miR-21 groups. Except for the Control group, the other 3 groups were exposed to self-made hyperoxia chamber containing 95%O2 to establish rat model of HALI. In 72 h after exposure, RT-qPCR was performed to detect the miR-21 expression in lung tissue and in AEC-Ⅱ-derived exosomes. HE staining was performed to observe morphological changes in lung tissue and to score the pathology of lung injury, and the wet/dry mass ratio of lung tissue and alveolar fluid clearance (AFC) were calculated. Superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were measured by visible spectrophotometry. The levels of reactive oxygen species (ROS) were measured by fluorescence spectrophotometry. The protein levels PTEN, AKT, p-AKT, PI3K and α-ENaC, β-ENaC, γ-ENaC were detected by Western blotting. Dual luciferase reporter gene assay was conducted to verify the relationship between miR-21 and PTEN targeting. Results The vesicular material extracted from primary cultured AEC-Ⅱ was identified as exosomes, the expression level of miR-21 was significantly increased in the exosomes (P < 0.05), and PTEN was identified as the target gene of miR-21. Compared with the mice of the Control group, thickening pulmonary septum, massive infiltration of inflammatory cells and alveolar atrophy were observed, and pathological score of lung injury, lung wet/dry mass ratio, and protein levels of MDA and PTEN were elevated in the the HALI group, HALI+miR-21 group and HALI+siPI3K+miR-21 group (P < 0.05). The protein expression levels of SOD, T-AOC, AFC, miR-21 and p-Akt, α-ENaC, β-ENaC, γ-ENaC were reduced in the above 3 groups (P < 0.05), significantly in the HALI+siPI3K+miR-21 group. HE staining showed that no significant differences in thickening of pulmonary septum and inflammatory cell infiltration were observed between the HALI+miR-21 group and the HALI group, but milder alveolar atrophy was seen in the former group. What's more, the former group also got obviously reduced pathological score of lung injury, lower lung wet/dry mass ratio, and decreased MDA and PTEN expression (P < 0.05), but increased protein levels of SOD, T-AOC, AFC, miR-21 and p-Akt, α-ENaC, β-ENaC, γ-ENaC (P < 0.05) when compared with the latter group. Conclusion Exosomal miR-21 derived from AEC-Ⅱ targets PTEN to activate PI3K/AKT signaling pathway, and attenuates hyperoxic acute lung injury by regulating epithelial sodium channels. [Key words] type Ⅱ alveolar epithelial cells , exosomes , microRNA-21-5p, epithelial sodium channels , hyperoxic acute lung injury , PI3K/Akt signaling pathway ,

Abstract User–item interactions on e-commerce platforms involve various intents, such as browsing and purchasing, which require fine-grained intent recognition. Existing recommendation methods incorporate latent intent into user–item interactions; however, they overlook important considerations. First, they fail to integrate intents with semantic information in knowledge graphs, neglecting intent interpretability. Second, they do not exploit the structural information from multiple views of latent intents in user–item interactions. This study established the intent with knowledge-aware multiview contrastive learning (IKMCL) model for explanation in recommendation systems. The proposed IKMCL model converts latent intent into fine-grained intent, calculates intent weights, mines latent semantic information, and learns the representation of user–item interactions through multiview intent contrastive learning. In particular, we combined fine-grained intents with a knowledge graph to calculate intent weights and capture intent semantics. The IKMCL model performs multiview intent contrastive learning at both coarse-grained and fine-grained levels to extract semantic relationships in user–item interactions and provide intent recommendations in structural and semantic views. In addition, an intent-relational path was designed based on multiview contrastive learning, enabling the capture of semantic information from latent intents and personalized item recommendations with interpretability. Experimental results using large benchmark datasets indicated that the proposed model outperformed other advanced methods, significantly improving recommendation performance.

Abstract Online recommendation systems process large amounts of information to make personalized recommendations. There has been some progress in research on incorporating knowledge graphs in reinforcement learning for recommendation; however, some challenges still remain. First, in these approaches, an agent cannot switch paths intelligently, because of which, the agent cannot cope with multi-entities and multi-relations in knowledge graphs. Second, these methods do not have predefined targets and thus cannot discover items that are closely related to user-interacted items and latent rich semantic relationships. Third, contemporary methods do not consider long rational paths in knowledge graphs. To address these problems, we propose a deep knowledge reinforcement learning (DKRL) framework, in which path-guided intelligent switching was implemented over knowledge graphs incorporating reinforcement learning; this model integrates predefined target and long logic paths over knowledge graphs for recommendation systems. Specifically, the designed novel path-based intelligent switching algorithm with predefined target enables an agent to switch paths intelligently among multi-entities and multi-relations over knowledge graphs. In addition, the weight of each path is calculated, and the agent switches paths between multiple entities according to path weights. Furthermore, the long logic path has better recommendation performance and interpretability. Extensive experiments with actual data demonstrate that our work improves upon existing methods.The experimental results indicated that DKRL improved the baselines of NDCG@10 by 3.7%, 9.3%, and 4.7%; of HR@10 by 12.39%, 20.8%, and 13.86%; of Prec@10 by 5.17%, 3.57%, 6.2%; of Recall@10 by 3.01%, 4.2%, and 3.37%. The DKRL model achieved more effective recommendation performance using several large benchmark data sets compared with other advanced methods.

Objective Objective To investigate the changes in hippocampal astrocytes and neuronal primary cilia, and neuronal apoptosis in the offspring brain of advanced maternal age and the role of LKB1/AMPK pathway. Methods The 12-month-old SD female rats were mated with 3-month-old SD male rats to produce offspring as the advanced maternal age (AMA) group, and the 3-month-old SD female rats were mated with 3-month-old SD males to produce offspring as the appropriate age (Control, Ctl) group. The following studies were conducted on postnatal days 14, 28 and 60 (P14, P28 and P60) in the 2 groups (14 rats per group at each time point, half males and half females). HE staining and Nissl staining were used to observe the changes in the morphology and the number of hippocampal neurons and their internal Nissl bodies. Immunofluorescence assay was employed to detect the expression of hippocampal primary cilia marker, anti-ADP ribosylation factor-like protein-13B (ARL13B), and Western blotting was applied to measure the expression of hippocampal intraflagellar transport protein 88 (IFT88) to assess functional changes in primary ciliogenesis. TUNEL staining and Western blotting were performed to detect the expression levels of pro-apoptotic BAX, and anti-apoptotic protein, BCL-2 to observe the changes of apoptosis in the hippocampus. Western blotting was also used to detect the expression levels of liver kinase B1 (LKB1), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and the levels of their corresponding phosphorylated proteins to assess LKB1/AMPK pathway changes. Results Compared with the Ctl group: HE staining and Nissl staining showed that the number of hippocampal neurons was significantly reduced in the AMA group at P14 (P < 0.05), and there were abnormal changes in hippocampal neuron morphology and Nissl body number and morphology in the AMA group at all time points; the incidence of ARL13B primary cilia was significantly decreased in the AMA group at both P14 (P < 0.05) and P28 (P < 0.001), and the length of ARL13B was obviously shortened in the AMA group at both P14 (P < 0.05) and P28 (P < 0.05); the hippocampal expression level of IFT88 was notably lower in the AMA group at the P14 (P < 0.01). TUNEL staining showed that the apoptotic rate of hippocampal neurons at P14 was remarkably higher in the AMA group (P < 0.05), while Western blotting indicated that the expression of BAX was significantly higher (P < 0.001) and that of BCL-2 was lower (P < 0.01). In the AMA group, the expression of p-LKB1 was significantly decreased at P14 (P < 0.05), that of p-AMPK was statistically elevated at P28 (P < 0.01) and P60 (P < 0.01), and that of p-mTOR was notably decreased at P60 (P < 0.05). Conclusion Neuronal damage, defective primary ciliogenesis and growth inhibition, and abnormal activation of apoptosis are present in the hippocampus of juvenile offspring brain of advanced maternal age. Meanwhile, the LKB1/AMPK pathway, which is regulated by primary cilia in hippocampal astrocytes and neurons of advanced maternal age offspring brain, is abnormally activated at all ages.

Abstract Background Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte‐mediated antitumor activity. Methods We conducted a retrospective cohort study to investigate the impact of PPAR‐γ‐activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers. Results A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non‐PPAR‐γ‐ARB users (n = 102), PPAR‐γ‐ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0—not reached] vs. 18.6 [IQR, 6.1–38.6] months) and progression‐free survival (17.3 [IQR, 5.1—not reached] vs. 8.2 [IQR, 2.4–18.6] months). In Cox regression analysis, the use of PPAR‐γ‐activating ARBs had an approximately 50% reduction in all‐cause mortality and disease progression. Patients who received PPAR‐γ‐activating ARBs also had higher clinical benefit rates than non‐PPAR‐γ‐ARB users (82% vs. 61%, p = 0.005). Conclusion The use of ARBs with PPAR‐γ‐activating property is linked with better survival among patients receiving ICIs.

Abstract Understanding substrate effects on spin dynamics and relaxation is of key importance for spin-based information technologies. However, the key factors that determine such effects, in particular for materials with strong spin-orbit coupling (SOC), have not been well understood. Here we performed first-principles real-time density-matrix dynamics simulations with SOC and the electron-phonon and electron-impurity scattering for spin lifetimes (τ s ) of supported/free-standing germanene, a prototypical strong SOC 2D Dirac material. We show that the effects of different substrates on τ s can surprisingly differ by two orders of magnitude. We find that substrate effects on τ s are closely related to substrate-induced modifications of the SOC-field anisotropy, which changes the spin-flip scattering matrix elements. We propose a new electronic quantity, named spin-flip angle θ ↑ ↓ , to characterize spin relaxation through intervalley spin-flip scattering. We find that $${\tau }_{s}^{-1}$$ τ s − 1 is approximately proportional to the averaged value of $${\sin }^{2}\left({\theta }^{\uparrow \downarrow }/2\right)$$ sin 2 θ ↑ ↓ / 2 , which serves as a guiding parameter of controlling spin relaxation.

Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer. Herein, we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib (Gefi), ferrocene (Fc) and dihydroartemisinin (DHA) for the combined therapy of both ferroptosis and apoptosis. In the tumor microenvironment, this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH. Interestingly, the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc, further executing tumor cell death with concomitant chemotherapy by Gefi. More importantly, this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis, as well as no noticeable side-effects during treatments. This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.

Defect centers in two-dimensional materials has shown promise for applications in quantum information and sensing. Lee et al. computationally discover a class of substitutional defect centers in monolayer transition metal dichalcogenides with promising qubit characteristics operating at telecom wavelengths.

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This “all-in-one” delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

High Cd pollution can damage plant physiology and seriously threaten ecological security and human health. Therefore, we designed a cropping system, arbuscular mycorrhizal fungi (AMF) - soybean - Solanum nigrum L., to solve the high Cd pollution problem in an environmentally and economically friendly way. The results showed that AMF were able to break free from the constraints of cocultivation and still promote plant photosynthesis and growth in combined treatments to resist Cd stress. In addition, cocultivation combined with AMF improved the antioxidant defense to scavenge reactive oxygen species by promoting the production of antioxidant enzymes and nonenzyme substances in host plants. The glutathione content in soybean and the catalase activity in nightshade were recorded at the highest values under cocultivation combined with AMF treatment, which were 23.68% and 129.12% higher than those of monoculture without AMF treatments. The improvement in antioxidant defense alleviated oxidative stress, which was manifested by the reduction in Cd dense electronic particles in the ultrastructure and a 26.38% decrease in MDA content. Furthermore, this cropping mode combined the advantages of cocultivation to improve the Cd extraction efficiency and Rhizophagus intraradices to limit Cd accumulation and transport so that Cd was more accumulated and restricted in the roots of the cocultivated Solanum nigrum L., and the Cd concentration in soybean beans was reduced by 56% compared with the soybean monoculture without AMF treatment. Therefore, we suggest that this cropping system is a comprehensive and mild remediation technology suitable for highly Cd-contaminated soil.

Abstract The therapeutic effect of chemotherapeutics such as gemcitabine against pancreatic cancer is considerably attenuated by immune-suppressive tumor microenvironment. Improvement of chemotherapeutic efficacy by targeting tumor-associated macrophage and reprograming tumor microenvironment to enhance their efficacy may become a promising strategy. To this end, we developed a biomimetic dual-targeting nanomedicine (PG@KMCM) where gemcitabine-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles are coated with a layer of bioengineered cancer cell membrane that stably expresses peptides targeting M2-like macrophages (M2pep) while reserving tumor-associated antigens (TAAs). The PG@KMCM nanomedicine enables the simultaneous targeted delivery of gemcitabine to pancreatic tumor sites and TAMs to potentiate its therapeutic effects. Furthermore, the combination of an immune checkpoint inhibitor (PD-L1 antibody) with PG@KMCM synergistically enhanced the anti-tumoral effect by reprogramming the immune-suppressive tumor microenvironment, including the elimination of PD-L1-positive macrophages and the downregulation of PD-L1 expression. Our study proved dual-targeting PG@KMCM nanomedicine in combination with PD-L1 immune checkpoint inhibitor therapy is able to effectively reprogram the tumor microenvironment and kill pancreatic cancer cells to enhance overall therapeutic potential. Graphical Abstract

The coexistence of numerous Mississippi Valley-type (MVT) Pb-Zn deposits and oil/gas reservoirs in the world demonstrates that a close genetic link between them. The northern Yunnan–Guizhou depression (NYGD) is a tectonic unit containing Pb–Zn deposits, paleo-oil reservoirs and shale gas. However, previous studies on the relationship between hydrocarbon accumulation and Pb–Zn mineralization have been ignored. The Maoping Pb–Zn deposit is a large-sized MVT deposit in the NYGD where a large amount of solid bitumen (i.e., a paleo-oil reservoir) occurs, and it is an ideal area to study the relationship between hydrocarbon accumulation and lead–zinc mineralization. In this paper, the bitumen and pyrite associated with bitumen from the Xujiazhai (discovered in this study) and Xiaocaoba paleo-oil reservoirs and the Maoping Pb–Zn deposit are researched. Geological observation has revealed that bitumen occurs in dissolution pores, fractures and intercrystalline pores in dolomite of the Upper Devonian and Carboniferous. The bitumen from Xujiazhai, Maoping and Xiaocaoba with high and similar Raman equivalent reflectance (RmcRo%) indicates they are in over-mature level and may be derived from the cracking of early-accumulated crude oils. The bitumen in the Xujiazhai paleo-oil reservoir and Maoping deposit has an abundant Pb and Zn content, indicating petroleum liquids may act as the transporting agents of metallogenic metal elements, carrying them to sites where mineralization may take place. The source rocks may have provided not only the oil for paleo-oil/gas reservoirs, but also a portion of ore metals for the Pb-Zn mineralization. The bacterial sulfate reduction (BSR) and thermochemical sulfate reduction (TSR) processes were recorded by the pyrite in the paleo-oil reservoir, which was consistent with the mechanism of reduced sulfur formation in the Maoping deposit. In addition, the large negative (−27.7‰ to −5.7‰) and positive (.9‰ to 19.2‰) δ34S values of the pyrite associated with the bitumen in the paleo-oil reservoir were similar to those of the sulfide in the Maoping deposit. We believe that the formation and evolution of the paleo-oil reservoirs are closely related to the metallogenic process of the Maoping Pb–Zn deposit, and the sulfides in them have the same sulfur source and formation mechanism as reduced sulfur. BSR phenomena could occur in prior to migration of the hydrocarbons into the reservoir or low mature oil stage in paleo-oil reservoir; a small amount of H2SBSR was combined with metal ions in ancient oil reservoirs and deposits to form early subhedral, xenomorphic granular, fine-grained strawberry aggregate pyrite and/or gelatinous sphalerite. The paleo-gas reservoir formed by the evolution of the paleo-oil reservoir in the main metallogenic period potentially participated in the mineralization; that is, organic gas acted as a reducing agent and transformed SO42− in the upper Devonian Zaige Formation gypsum strata on the periphery of the Maoping lead–zinc mining area into H2STSR through TSR, providing reduced sulfur and creating the environmental conditions for mineralization. During or after the transformation of the paleo-oil reservoir to a paleo-gas reservoir, the decoupling of metals and organic complexes may have provided the ore metals for mineralization. Massive sulfide precipitation may have occurred during or after the paleo-oil reservoir cracked into the paleo-gas reservoir.

IntroductionSoil salinization has become one of the most serious environmental issues globally. Excessive accumulation of soluble salts will adversely affect the survival, growth, and reproduction of plants. Elaeagnus angustifolia L., commonly known as oleaster or Russian olive, has the characteristics of tolerance to drought and salt. Arbuscular mycorrhizal (AM) fungi are considered to be bio-ameliorator of saline soils that can enhance the salt tolerance of the host plants. However, there is little information on the root proteomics of AM plants under salt stress.MethodsIn this study, a label-free quantitative proteomics method was employed to identify the differentially abundant proteins in AM E. angustifolia seedlings under salt stress.ResultsThe results showed that a total of 170 proteins were significantly differentially regulated in E.angustifolia seedlings after AMF inoculation under salt stress. Mycorrhizal symbiosis helps the host plant E. angustifolia to respond positively to salt stress and enhances its salt tolerance by regulating the activities of some key proteins related to amino acid metabolism, lipid metabolism, and glutathione metabolism in root tissues.ConclusionAspartate aminotransferase, dehydratase-enolase-phosphatase 1 (DEP1), phospholipases D, diacylglycerol kinase, glycerol-3-phosphate O-acyltransferases, and gamma-glutamyl transpeptidases may play important roles in mitigating the detrimental effect of salt stress on mycorrhizal E. angustifolia . In conclusion, these findings provide new insights into the salt-stress tolerance mechanisms of AM E. angustifolia seedlings and also clarify the role of AM fungi in the molecular regulation network of E. angustifolia under salt stress.

Abstract Format‐preserving encryption (FPE) allows encrypting plaintexts while preserving a specific format. In Selected Areas in Cryptography 2018, two targeted ciphers were proposed as new FPE schemes. The second scheme was designed with an algorithm called Mix–Swap–Unmix that is shown to be equivalent to a particular matching exchange process under a specific setting. In this comment paper, we prove that the matching exchange process is invalid. As a result, this equivalence does not exist.

Drawing on the notion of cultural translation and agenda-setting theory, this study examines the role that translation plays in facilitating cross-linguistic and cross-cultural communication within the context of news translation. It is based on a case study of Culture Weekly—a four-page section published every Monday in Reference News, the most widely circulated daily newspaper in China. This study analyzes a comparable corpus of Chinese news articles from Culture Weekly and their English-language versions from various media outlets between February and March 2022. The study finds that the newspaper mainly used strategies of acculturation and literal translation and that it set the agenda for its domestic readers by highlighting particular cultural issues and disseminating certain cultural values. This case study provides insight into how news translation, as a form of recontextualization, strikes a delicate balance between accuracy and acceptability and how it mediates between source and target cultures within the institutional setting. The resulting translation reflects the editorial attitudes of the media outlet toward various cultural issues and manifests the relationship between the newspaper and its readership.

A novel method, termed ladder-shape melting temperature isothermal amplification (LMTIA), was developed in this study. As a proof of concept, one pair of primers or two pairs of nested primers and a thermostable DNA polymerase were employed to amplify the internal transcribed spacer of Oryza sativa with the ladder-shape melting temperature curve. Our results demonstrated that the LMTIA assay with nested primers was 50-fold more sensitive than the LAMP assay with the same level of specificity. The LMTIA method has the potential to be used for the prevention and control of emerging epidemics caused by different types of pathogens.

Abstract Background The prediction of long non-coding RNA (lncRNA) has attracted great attention from researchers, as more and more evidence indicate that various complex human diseases are closely related to lncRNAs. In the era of bio-med big data, in addition to the prediction of lncRNAs by biological experimental methods, many computational methods based on machine learning have been proposed to make better use of the sequence resources of lncRNAs. Results We developed the lncRNA prediction method by integrating information-entropy-based features and machine learning algorithms. We calculate generalized topological entropy and generate 6 novel features for lncRNA sequences. By employing these 6 features and other features such as open reading frame, we apply supporting vector machine, XGBoost and random forest algorithms to distinguish human lncRNAs. We compare our method with the one which has more K-mer features and results show that our method has higher area under the curve up to 99.7905%. Conclusions We develop an accurate and efficient method which has novel information entropy features to analyze and classify lncRNAs. Our method is also extendable for research on the other functional elements in DNA sequences.

Abstract Despite the recognition of two-dimensional (2D) systems as emerging and scalable host materials of single-photon emitters or spin qubits, the uncontrolled, and undetermined chemical nature of these quantum defects has been a roadblock to further development. Leveraging the design of extrinsic defects can circumvent these persistent issues and provide an ultimate solution. Here, we established a complete theoretical framework to accurately and systematically design quantum defects in wide-bandgap 2D systems. With this approach, essential static and dynamical properties are equally considered for spin qubit discovery. In particular, many-body interactions such as defect–exciton couplings are vital for describing excited state properties of defects in ultrathin 2D systems. Meanwhile, nonradiative processes such as phonon-assisted decay and intersystem crossing rates require careful evaluation, which competes together with radiative processes. From a thorough screening of defects based on first-principles calculations, we identify promising single-photon emitters such as SiVV and spin qubits such as TiVV and MoVV in hexagonal boron nitride. This work provided a complete first-principles theoretical framework for defect design in 2D materials.

One major challenge for antiferromagnetic spintronics is how to control the antiferromagnetic state. Here Jani et al. demonstrate the reversible ionic control of the room-temperature magnetic anisotropy and spin reorientation transition in haematite, via the incorporation and removal of hydrogen.

The origin of the charge density wave (CDW) in transition metal dichalcogenides has been hotly debated, and no conclusive agreement has been reached. Here, we propose an ab initio framework for an accurate description of both Fermi surface nesting and electron-phonon coupling (EPC) and systematically investigate their roles in the formation of the CDW. Using monolayer 1H-NbSe_{2} and 1T-VTe_{2} as representative examples, we show that it is the momentum-dependent EPC that softens the phonon frequencies, which become imaginary (phonon instabilities) at CDW vectors (indicating CDW formation). In addition, the distribution of the CDW gap opening (electron instabilities) can be correctly predicted only if EPC is included in the mean-field model. These results emphasize the decisive role of EPC in the CDW formation. Our analytical process is general and can be applied to other CDW systems.

Abstract Cloud storage with sharing services is increasingly popular among data owners. However, it is difficult for the users to know if the cloud server providers (CSPs) indeed protect their data. To verify data integrity and preserve data and key privacy in the group, this paper proposes a new threshold hybrid encryption for integrity auditing method without trusted center. The proposed method is developed based on the Advanced Encryption Standard (AES) and the Elliptic Curve Cryptography (ECC) with Shamir secret sharing. In this way, the key can be distributed and managed without trusted center, preserving the privacy of the key of the AES and users’ private key. Besides, we design and implement a novel integrity auditing and re-signature method which verifies the data integrity and solves the collusion question of the cloud and the revoked users. Security analysis and performance evaluation demonstrate that the proposed scheme realizes the correctness, security, and efficiency with a low communication and computation cost.

The progression and malignancy of many tumors are associated with increased tissue stiffness. Conversely, the oncogenically transformed cells can be confined in soft stroma. Yet, the underlying mechanisms by which soft matrix confines tumorigenesis and metastasis remain elusive. Here, we show that pancreatic cancer cells are suppressed in the soft extracellular matrix, which is associated with YAP1 degradation through autophagic-lysosomal pathway rather than Hippo signal mediated proteasome pathway. In the soft stroma, PTEN is upregulated and activated, which consequently promotes lysosomal biogenesis, leading to the activation of cysteine-cathepsins for YAP1 degradation. In vitro, purified cathepsin L can directly digest YAP1 under acidic conditions. Lysosomal stress, either caused by chloroquine or overexpression of cystatin A/B, results in YAP1 accumulation and malignant transformation. Likewise, liver fibrosis induced stiffness can promote malignant potential in mice. Clinical data show that down-regulation of lysosomal biogenesis is associated with pancreatic fibrosis and stiffness, YAP1 accumulation, and poor prognosis in PDAC patients. Together, our findings suggest that soft stroma triggers lysosomal flux-mediated YAP1 degradation and induces cancer cell dormancy.

First-principles calculations can help design and understand the behaviour of quantum technologies, but this requires the development of accurate methods to predict material properties. Here the authors present a method for calculating the spin-phonon relaxation time of general systems, a key quantity for spintronic devices.

Studying the similarities between the concepts in a knowledge graph can be useful in making friend recommendations on various microblogging platforms. Most existing approaches that only focus on accurate friend recommendation and can not give a reasoning explaining. In addition, existing similarity measurements are too costly and ineffective to be used in practical applications. To solve these problems, we purposed the shortest path-guide reasoning path, we perform explicit reasoning with knowledge for decision making so that the friend recommendation are supported by an interpretable causal inference. Then we designed a novel Weighted Euclidean-Shortest Path (WESP) method for measuring concept similarity in a knowledge graph and applied it to friend recommendations on a microblogging platform. First we took the shortest path as an example to measure concepts similarity. Although it was easy to use the shortest path to measure the similarity between concept pairs, the results of the measurements via the shortest path were affected by local structural imbalance in the knowledge graph. The imbalance had a significant impact on measuring concepts similarity; the more balanced the local structure, the greater similarity between the concept pairs. Then, we applied the WESP method to friend recommendations on the microblogging platform. We use the optimization similarity measurement (OSM) model that calculated the similarity between corresponding concept pairs. Our experimental results showed that the OSM method achieved better performance than the baseline methods in making friend recommendations.

While H2 evolution from water may serve as a renewable source of fuel, there are a limited number of catalysts that are stable and active in alkaline media. Here, authors find carbon doping of NiO to increase the number of favorable sites for H2 evolution and boost electrocatalytic performances.

Objective: To explore the pharmacodynamic mechanism of Fu Zi Li Zhong Decoction (FZLZD) in treating gastric ulcer and its effect on gastrointestinal microecology. Methods: Rat gastric ulcer model was established by continuous vinegar gavage. The experiment included normal group, model group, ranitidine group and FZLZD group. The animals were handled after intragastricing administration of corresponding clinical isodose drugs for 7 d. The rats’ gastrointestinal histopathology was observed by HE staining. The expression of ZO-1 and Occludin mRNA in rat gastric tissue was detected by RT-PCR. The diversity of intestinal flora was analyzed by 16SrDNA sequencing. Results: FZLZD can effectively improve gastric mucosal destruction, epithelial exfoliation, inflammatory cell infiltration, inflammatory substance exudation and edema in rats with gastric ulcer. FZLZD can effectively up-regulate the expression levels of ZO-1 and Occludin mRNA in gastric tissue of rats with gastric ulcer. The results of intestinal flora diversity showed that the diversity of intestinal flora in FZLZD group was significantly higher than that of model group. Conclusions: FZLZD can regulate gastric ulcer by promoting the expression of ZO-1 and Occludin and improving the diversity of intestinal flora. Keywords: Fu Zi Li Zhong Decoction (FZLZD) Gastric ulcer, ZO-1, Occludin, Intestinal flora diversity, 16SrDNA

Mirror twin boundaries (MTBs) have been observed as metallic line defects in 2D transition metal dichalcogenides, but their chemical properties are not well understood. Here, the authors show that MTB defect networks on MoSe2 are more chemically reactive to organic molecules than pristine domains, and can template the self-assembly of hexagonal organic porous structures.

Abstract Background Numerous essential algorithms and methods, including entropy-based quantitative methods, have been developed to analyze complex DNA sequences since the last decade. Exons and introns are the most notable components of DNA and their identification and prediction are always the focus of state-of-the-art research. Results In this study, we designed an integrated entropy-based analysis approach, which involves modified topological entropy calculation, genomic signal processing (GSP) method and singular value decomposition (SVD), to investigate exons and introns in DNA sequences. We optimized and implemented the topological entropy and the generalized topological entropy to calculate the complexity of DNA sequences, highlighting the characteristics of repetition sequences. By comparing digitalizing entropy values of exons and introns, we observed that they are significantly different. After we converted DNA data to numerical topological entropy value, we applied SVD method to effectively investigate exon and intron regions on a single gene sequence. Additionally, several genes across five species are used for exon predictions. Conclusions Our approach not only helps to explore the complexity of DNA sequence and its functional elements, but also provides an entropy-based GSP method to analyze exon and intron regions. Our work is feasible across different species and extendable to analyze other components in both coding and noncoding region of DNA sequences.

Electrochemical water splitting is promising for sustainable energy, but relies on development of electrocatalysts for hydrogen evolution. Here the authors report nitrogen- and ruthenium-codoped carbon nanowires in which ruthenium atoms in a carbon matrix drive electrocatalysis of hydrogen evolution

Without effective cryptographic mechanisms, the wireless channel between the USB/uploader and insulin pump frequently suffers from vulnerabilities. Either eavesdropping or therapy manipulation attacks would put the patients in a life-threatening situation. Towards tackling this problem, we propose an access control scheme by introducing feature fusion and voiceprint. Featured by the anti-replay speaker verification and voiceprint-based key agreement, it secures communications over the wireless channel. Through a cascaded fusion of speaker verification and anti-replay countermeasure, the anti-replay speaker verification guarantees that the pump can only be accessed after the verification. When defending against zero-effort and replay impostors with our scheme, the equal error rate can be reduced to 2.22%. Furthermore, to generate a common key for the wireless channel, in the voiceprint-based key agreement, we present a non-interactive energy-difference-based voiceprint extraction and adaptive Reed-Solomon coding based fuzzy extractor. Thus, it enhances the communication encryption which protects the pump from eavesdropping and therapy manipulation attacks. Also, with an appropriate constraint on voiceprints similarity, the key agreement lowers the risk of channel establishment from device locating outside the pump's close proximity.

Fully homomorphic encryption (FHE) has been regarded as the holy grail of cryptography and supports meaningful computations on encrypted data. Recently, Kumer et al. proposed a symmetric FHE scheme based on the Euler theorem. However, we illustrate in the paper that the secret key can be recovered from the homomorphic computation key and only a pair of known plaintext/ciphertext by computing the greatest common divisor with the Euclidean algorithm. Our observations are well supported by the numerical experiments on the suggested parameters. Furthermore, an improvement in the scheme is presented. We mimic Dijk et al.'s idea to illustrate that the improvement can be reduced to the approximate greatest common divisor (AGCD) problem. Several known attacks, including the proposal in this paper, are also examined.

Due to the remarkable capability in handling arbitrary cluster shapes, support vector clustering (SVC) benefits data analysis in terms of data description. However, large-scale data such as network traffic frequently makes it suffer from highly intensive pricey computation and storage for solving the dual problem and storing the kernel matrix, respectively. Fortunately, support vectors which describe the clusters, in a sense, are expected in the boundaries. To tackle this issue, we propose an efficient training SVC with appropriate boundary information (ETSVC), which features excellent flexibility and scalability. In ETSVC, we first give a shrinkable boundary selection (SBS) method which collects appropriate boundaries while reducing redundancy and noise. Based on the boundary information, a redefined dual problem is then designed without scarifying the principle of SVC. Finally, we design a reformative solver (RSolver) to reformulate the training phase, which estimates the support vector function by solving the dual problem. Since only a subset of boundaries is employed for model training, theoretical analysis suggests that ETSVC reaches efficiency improvement and consumes much less memory if sacrificing efficiency to reduce storage consumption. Towards grouping P2P flows and large-scale intrusion traffic, as well as other non-traffic data, experimental results confirm that ETSVC could be applied to resources constrained platform while achieving comparable accuracies with the state-of-the-art methods.

Finite mixture models based on the symmetric Gaussian distribution have been applied broadly in data analysis. However, not all the data in real-world applications can be safely supposed to have a symmetric Gaussian form. This paper presents a new mixture model that includes the inverted Beta mixture model (IBMM) as a special case to analyze the positive non-Gaussian data. The advantage of the proposed model is that the number of the model parameters is variable and infinite. Consequently, the proposed model is adaptable to the size of the data. On the basis of the recently proposed extended variational inference (EVI) framework, we develop a closed-form solution to approximate the posterior distributions. The performance and the effectiveness of the proposed model are demonstrated with the real data generated from two challenging applications, namely, image classification and object detection.

Recent progress has been made on the synthesis and characterization of metal halide perovskite magic-sized clusters (PMSCs) with ABX3 composition (A=CH3NH3+ or Cs+, B=Pb2+, and X=Cl−, Br-, or I-). However, their mechanism of growth and structure is still not well understood. In our effort to understand their structure and growth, we discovered that a new species can be formed without the CH3NH3+ component, which we name as molecular clusters (MCs). Specifically, CH3NH3PbBr3 PMSCs, with a characteristic absorption peak at 424 nm, are synthesized using PbBr2 and CH3NH3Br as precursors and butylamine (BTYA) and valeric acid (VA) as ligands, while MCs, with an absorption peak at 402 nm, are synthesized using solely PbBr2 and BTYA, without CH3NH3Br. Interestingly, PMSCs are converted spontaneously overtime into MCs. An isosbestic point in their electronic absorption spectra indicates a direct interplay between the PMSCs and MCs. Therefore, we suggest that the MCs are precursors to the PMSCs. From spectroscopic and extended X-ray absorption fine structure (EXAFS) results, we propose some tentative structural models for the MCs. The discovery of the MCs is critical to understanding the growth of PMSCs as well as larger perovskite quantum dots (PQDs) or nanocrystals (PNCs).

Due to the introduction of memristors, the memristor-based nonlinear oscillator circuits readily present the state initial-dependent multistability (or extreme multistability), i.e., coexisting multiple attractors (or coexisting infinitely many attractors). The dimensionality reduction modeling for a memristive circuit is carried out to realize accurate prediction, quantitative analysis, and physical control of its multistability, which has become one of the hottest research topics in the field of information science. Based on these considerations, this paper briefly reviews the specific multistability phenomenon generating from the memristive circuit in the voltage-current domain and expounds the multistability control strategy. Then, this paper introduces the accurate flux-charge constitutive relation of memristors. Afterwards, the dimensionality reduction modeling method of the memristive circuits, i.e., the incremental flux-charge analysis method, is emphatically introduced, whose core idea is to implement the explicit expressions of the initial conditions in the flux-charge model and to discuss the feasibility and effectiveness of the multistability reconstitution of the memristive circuits using their flux-charge models. Furthermore, the incremental integral transformation method for modeling of the memristive system is reviewed by following the idea of the incremental flux-charge analysis method. The theory and application promotion of the dimensionality reduction modeling and multistability reconstitution are proceeded, and the application prospect is prospected by taking the synchronization application of the memristor-coupled system as an example.