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Objective To elucidate the underlying mechanisms of sperm-associated antigen 6(SPAG6) in the proliferation and drug resistance of B-cell acute lymphoblastic leukemia (B-ALL). Methods A total of 56 B-ALL patients and 15 iron-deficiency anemia (IDA) patients admitted in the First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023 were recruited and served as the experimental and control groups, respectively.Bone marrow mononuclear cells (BMMNCs) were derived from the bone marrow tissues of the experimental group.According to the results of qRT-PCR for the expression of SPAG6 in the obtained BMMNCs, the B-ALL patients were stratified into newly-diagnosed (New-diag) group, complete remission (CR) group, minimal residual disease Possitive (MRD+) group, and relapse group.Lentiviral vectors were used to construct B-ALL cells with SPAG6 overexpression and knockdown.CCK-8 assay and methylcellulose-based colony formation experiment were employed to assess the survival, proliferation, and clonogenic potential of the cells with varying SPAG6 expression levels.After f B-ALL cells were treated with the chemotherapeutic drugs, daunorubicin (DNR) and methotrexate (MTX), CCK-8 assay, flow cytometry and Western blot analysis were applied to detect cell viability (drug sensitivity and IC50), cell apoptosis, and protein levels of apoptosis-related molecules Bax, Caspase-3 and Bcl-2, respectively.The mRNA-seq profiles of B-ALL patients were obtained from the TARGET database, and gene set enrichment analysis (GSEA) was conducted to explore SPAG6-associated signaling pathways, which were subsequently validated experimentally.After treatment with the NF-κB agonist Phorbol 12-myristate 13-acetate (PMA) and the antagonist BAY-11-7082, cell viability and sensitivity to chemotherapeutic drugs were assessed with CCK-8 assay, and the expression of pathway-related proteins NF-κB P65, p-NF-κB p65, IKBα, p-IKBα, TNF-α, and EPO was detected by Western blot analysis.A mouse xenograft tumor model was constructed in SPAG6-/+ knockdown mice to observe the effect of DNR on tumor growth and the expression of the NF-κB signaling pathway in the tumor tissues with immunohistochemical assay. Results The mRNA level of SPAG6 was significantly higher in the B-ALL patients (P < 0.05), and in the MRD group (P=0.001) and R group (P=0.003) than the CR group.SPAG6 overexpression and knockdown in B-ALL cells confirmed that SPAG6 promoted the proliferation (P < 0.05) and decreased the sensitivity to DNR and MTX (P < 0.05).SPAG6 resisted chemotherapy-induced apoptosis in B-ALL cells by down-regulating pro-apoptotic proteins Bax and Caspase-3(P < 0.05), and up-regulating the expression of anti-apoptotic protein Bcl-2(P < 0.05).GSEA analysis suggested that the NF-κB pathway was enriched in B-ALL cells, and our experiments confirmed that SPAG6 enhanced the chemoresistance of B-ALL cells to chemotherapy by activating the NF-κB/TNF-α pathway.In in vivo experiments, knocking SPAG6 down significantly reduced the volume of transplanted tumors (P < 0.05), and an additional decrease in tumor growth was observed in the DNR-combined treatment group (P < 0.05), with reduced levels of NF-κB P65 and p-IKBα by immunohistochemical assay. Conclusion SPAG6 promotes the proliferation of B-ALL cells and reduces their chemosensitivity via the NF-κB/TNF-α pathway, suggesting a close association of SPAG6 with the therapeutic outcomes and prognosis in B-ALL patients.

Objective To prepare FLIVIGSII peptide (FI peptide) and investigate its physicochemical properties and hemostatic effect in vivo and in vitro. Methods The self-assembling peptide-based hydrogels were prepared by the FI peptide mixed with water. After gross observation for the hydrogel state of the FI peptide, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used for its microstructure, and dynamic light scattering (DLS) was performed for its size. The hemostatic effect of FI peptide after being mixed with blood samples treated with 3.8% sodium citrate was observed, and the microstructure of the blood clot was observed with SEM. CCK-8 assay and hemolysis assay were performed to verify its biocompatibility. After a rat model of hepatic parenchymal perforation and hemorrhage was established, 15 female SD rats (6~8 weeks old, weighing 150 g) were randomly divided into control group, FI peptide group and fibrin sealant group. The hemostatic effect of FI peptide and prognosis was observed and analyzed after treatment in each group, and the hemostatic mechanism was also investigated. Results FI peptides were successfully prepared, and it could rapidly self-assemble into a nanofiber network hydrogel in water, and further cause formation of blood clots. SEM showed that FI peptides self-assembled to form fibrous hydrogels after mixing with water. TEM results verified that the FI peptide formed into nanofibers in a diameter of 13.70±2.31 nm after gelatinization in water, and DLS results verified that the FI peptide formed polydisperse and multi-size nanofibers in water (in a range of 148.2~208.0 nm or 575.0~807.0 nm). The fibrous hydrogel formed by the FI peptide mixed with the blood could envelop the red blood cells, thus form a physical hemostatic barrier to achieve blood clotting in seconds. FI peptide hydrogel had no cytotoxicity to normal hepatocytes (L-O2 cells) and did not cause hemolysis of red blood cells. In in vivo experiment, FI peptide quickly formed nanofiber hydrogel when in contact with blood, thus formed physical hemostasis barrier to achieve hemostasis within a few seconds (hemostasis time < 5 s). Conclusion The FI peptide exhibits a rapid and efficient hemostatic effect, indicating a promising clinical application in the hemostasia of hepatic parenchymal traumatic hemorrhage.

Abstract Cloud computing enables highly configurable and reliable computing resources on a rentable per-use scheme, facilitating quick and cost-effective provisioning of large-scale applications. Thanks to the fast-paced evolution of cutting-edge technologies and the rapid spread of cloud-based solutions, the cloud computing ecosystem is now part of our everyday lives. Nevertheless, cloud computing relies on highly sophisticated data centers comprising energy-consuming servers and equipment that require much energy. Stimulating cloud services for active participation and network contributions presents several challenges. Strategies based on artificial intelligence (AI), game theory, and blockchain have great potential to create an economically sustainable cloud ecosystem. This paper explores strategies grounded in AI, game theory, and blockchain to foster an economically sustainable cloud ecosystem. Informed by a survey study, our research delves into incentive approaches within cloud computing. Theoretical foundations, motivations, and enabling techniques are comprehensively examined to provide valuable insights for a broad audience. The primary contributions of this work lie in elucidating the application of AI, game theory, and blockchain to address challenges in incentivizing cloud services, paving the way for a more sustainable and efficient cloud computing landscape.

When designing the retractable landing gear of an aircraft oil-gas mixed type，the medium flow characteristics between the inner cavities should be fully considered. The damping aperture and fuel filling amount of a certain UAV landing gear buffer is taken as the research object，and the single factor experimental method is used to analyze the changes of gas-liquid flow inside the buffer caused by each factor. The gas-liquid characteristics of the buffer under different damping apertures and oil filling amounts in the lowering stage are simulated and calculated by Fluent software. The results show that the damping hole oil flow during the landing gear lowering process is only related to the size of the pore size，not affected by the oil filling amount of the buffer. Under the 637 mL oil filling required by this type of UAV，the buffer damping aperture should be greater than 6 mm. For other types of landing gear buffers，when the oil filling amount is determined，the gas-liquid filling of the buffer that meets the lowering stage should be used as one of the buffer damping hole design criteria.

The activation of hepatic stellate cells (HSCs) is regarded as the primary driving factor of liver fibrosis. miR-192, a miRNA associated with hepatocellular carcinoma and enriched in HSCs, has an undisclosed role in HSC activation and liver fibrosis. In this study, a CCl4-induced rat liver fibrosis model and transforming growth factor-beta 1 (TGF-β1)-treated HSC lines (LX-2 and HSC-T6) were used to detect miR-192 and Rictor levels in vivo and in vitro. Bioinformatic analysis and a dual luciferase assay were used to predict and confirm the interaction of Rictor with miR-192. Gain- and/or loss-of-function methods evaluated molecular changes and HSC activation phenotypes, detected by quantitative real-time PCR, western blotting, and immunofluorescence. We observed a gradual downregulation of miR-192 and upregulation of Rictor during CCl4-induced liver fibrosis/cirrhosis in rats. Enriched miR-192 was downregulated, while Rictor was upregulated in TGF-β1-activated HSCs. miR-192 inhibited the activation of HSCs by directly targeting Rictor. High miR-192/low Rictor expression attenuated the fibrotic-related gene expression by AKT/mTORC2 signaling. In conclusion, miR-192 could inhibit the activation of HSCs by directly targeting Rictor in the AKT/mTORC2 signaling pathway. This study provides insights into potential therapeutic targets for liver fibrosis and cirrhosis.

Coherent perfect absorption (CPA), as time-reversed lasing, arises from appropriate wave interference within absorbers, offering flexible control over wave absorption. Typically, this control involves tuning the phase difference between two counter-propagating incident beams. Here, we elucidate the critical role of defect connectivity within three-dimensional zero-index media for realizing and controlling CPA. Specifically, the realization of CPA critically depends on the establishment of long-range connectivity of defects in a specific direction. Once the long-range connectivity is established, the CPA exhibits remarkable resilience against defects’ deformation, changes in size and shape of the zero-index media, as well as variations in number and orientation of incident channels. Notably, a minor disruption to this connectivity will result in a complete reduction of absorption to zero, highlighting an ultra-sensitive absorption property in response to connectivity perturbations. Our findings not only unveil a physical mechanism for realizing CPA but also open up promising avenues for advanced CPA control with versatile functionalities.

C24H18O3, monoclinic, P21/c (no. 14), a = 9.0474(7) Å, b = 19.9648(12) Å, c = 10.7153(3) Å, β = 104.175(2)°, V = 1876.6(3) Å3, Z = 4, Rgt(F) = 0.0459, wRref(F2) = 0.1183, T = 296 K.

In the rapidly evolving live broadcast economy, Key Opinion Leaders (KOLs) are reshaping e-commerce by promoting products in real-time. Our study investigates this phenomenon using a sophisticated model of user interaction and behavior guidance among KOLs. By proposing a multichannel decision-making model that includes KOLs, brands, and traditional retailers, we aim to understand the dynamics of profit-driven decisions and their impacts. Analyzing data from 25 KOL anchors, we find a notable trend. Despite positive skewness in daily sales and conversion rates, there’s a range of fluctuation (0 to 13) that hints at diminishing returns from KOL live broadcasts, ultimately affecting the effectiveness of influencing consumer behavior.

This study addresses the challenge of variable selection in partially linear additive spatial autoregressive models through a novel approach that leverages orthogonal projection based on the QR decomposition technique. This method ensures the validity and compatibility of examining the influence of e-commerce on rural high-quality development while minimizing bias in spatial spillover benefits analysis. By constructing a comprehensive evaluation index system, the research applies a partially linear weighted spatial autoregressive model with orthogonal projection to assess e-commerce’s impact on rural development. Analysis of baseline regression for selected villages, supplemented by heterogeneity tests, threshold effects, and spatial analyses, reveals a significant relationship: a one-unit increase in e-commerce activity corresponds to a 0.0038 unit increase in high-quality rural development. This growth comprises both a direct effect of 0.0011 units and a spillover effect of 0.0027 units, highlighting e-commerce’s pivotal role in promoting rural prosperity and its beneficial spillover to adjacent areas.

The rural revitalization strategy is underway and can provide the promotion of high-quality growing rural e-commerce as well as supply the facilities and industrial support required for its growth. The complete score of the rural e-commerce development level was assessed using the entropy value technique by analyzing data from 31 Chinese provinces, municipalities, and autonomous regions. The efficiency of rural e-commerce growth was evaluated using the BCC model and the super-efficient DEA model within the DEA model. The study examined the effects of rural revival on the effectiveness of electronic commerce in rural development. Both input and output views were considered when selecting the related factors. After that, the productivity value was examined by merging information on the growth of rural e-commerce between 2016 and 2020. The research indicates that between 2015 and 2022, the comprehensive score of rural e-commerce growth experienced a high-quality increase of 173.50%. Furthermore, 8 out of 31 provinces, municipalities, and autonomous areas had DEA-achieved e-commerce development efficiency, with a mean complete efficiency score of 0.700. However, the mean value of total efficiency decreased by 35.29% when the progress level of rural rejuvenation was eliminated. Apart from providing support for infrastructure construction, rural revitalization can also provide policy assurances and an industrial base for the expansion of rural electronic commerce.

Patients with castration-resistant prostate cancer (CRPC) often develop drug resistance after treatment with enzalutamide. The goal of our study was to identify the key genes related to enzalutamide resistance in CRPC and to provide new gene targets for future research on improving the efficacy of enzalutamide. Differential expression genes (DEGs) associated with enzalutamide were obtained from the GSE151083 and GSE150807 datasets. We used R software, the DAVID database, protein–protein interaction networks, the Cytoscape program, and Gene Set Cancer Analysis for data analysis. The effect of RAD51 knockdown on prostate cancer (PCa) cell lines was demonstrated using Cell Counting Kit-8, clone formation, and transwell migration experiments. Six hub genes with prognostic values were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which were significantly associated with immune cell infiltration in PCa. High RAD51, BLM, EXO1, and RFC2 expression was associated with androgen receptor signaling pathway activation. Except for APOE, high expression of hub genes showed a significant negative correlation with the IC50 of Navitoclax and NPK76-II-72-1. RAD51 knockdown inhibited the proliferation and migration of PC3 and DU145 cell lines and promoted apoptosis. Additionally, 22Rv1 cell proliferation was more significantly inhibited with RAD51 knockdown than without RAD51 knockdown under enzalutamide treatment. Overall, six key genes associated with enzalutamide resistance were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which are potential therapeutic targets for enzalutamide-resistant PCa in the future.

To prevent the crosstalk between adjacent waveguides in photonic integrated circuits, the minimum thickness of the cladding layers is around half a wavelength, which imposes a fundamental limitation to further integration and miniaturization of photonic circuits. Here, we reveal that epsilon-near-zero claddings, either isotropic or anisotropic, can break the above bottleneck by prohibiting the crosstalk for the modes with magnetic field polarized in the z direction at a deep-subwavelength thickness (e.g., λ 0/30, λ 0 is the free-space wavelength), therefore bestowing ultra-compact waveguide systems. The physical origin of this remarkable effect attributes to the divergent impedance of epsilon-near-zero materials far beyond those of dielectric or epsilon-negative claddings. Through full-wave simulations and microwave experiments, we have verified the effectiveness of the ultrathin epsilon-near-zero cladding in crosstalk prohibition. Our finding reveals the significant impact of impedance difference in waveguide designs and opens a promising route toward ultra-compact photonic chips.

The scattering matrix is the mathematical representation of the scattering characteristics of any scatterer. Nevertheless, except for scatterers with high symmetry like spheres or cylinders, the scattering matrix does not have any analytical forms and thus can only be calculated numerically, which requires heavy computation. Here, we have developed a well-trained deep neural network (DNN) that can calculate the scattering matrix of scatterers without symmetry at a speed thousands of times faster than that of finite element solvers. Interestingly, the scattering matrix obtained from the DNN inherently satisfies the fundamental physical principles, including energy conservation, time reversal and reciprocity. Moreover, inverse design based on the DNN is made possible by applying the gradient descent algorithm. Finally, we demonstrate an application of the DNN, which is to design scatterers with desired scattering properties under special conditions. Our work proposes a convenient solution of deep learning for scattering problems.

Objective: This study aimed to improve the application range and bioavailability of ursolic acid. Methods: The W/O/W pickering emulsion was prepared by a two-step process with ursolic acid as emulsifier and pectin as external aqueous phase. The preparation conditions of W/O emulsion were optimized by a single factor experiment, and the effects of pectin mass concentration on physicochemical properties, microstructure, rheological properties and long-term stability of W/O/W pickering emulsion were studied. Results: The optimal preparation technology of W/O emulsion was ursolic acid mass concentration of 4 g/100 mL, water-oil mass ratio of 2∶3, homogenization speed of 9 000 r/min, homogenization time of 5 min. The particle size of the double emulsion prepared with pectin as the external aqueous phase was between 30～40 μm. The absolute value of zeta potential, rheological property and storage stability of the emulsion at 4 ℃ were significantly improved with the increase of pectin mass concentration. Conclusion: The stable pickering double emulsion could be prepared when the mass concentration of pectin was 0.3, 0.4, 0.5 g/100 mL.

In order to improve the photocatalytic activity and practical use of titanium dioxide, the titanium dioxide/graphene aerogel (TGA) was prepared successfully by a mixture of sol-gel and solvothermal method. The obtained materials were characterized by SEM, XRD, FT-IR, BET analysis, etc. The influence of the amount of graphene on the photocatalytic activity of the material was investigated. The methylene blue (MB) was used as the simulated pollutant to evaluate the photocatalytic activity of the prepared materials. The results showed that when the amount of graphene was 30% of TiO2 the obtained material exhibited the highest photocatalytic activity and good reusability, with a degradation of 99.5% of MB after exposure to 500 W xenon light for 120 min. In this study, the 3D structure of graphene aerogel inhibited the agglomeration of TiO2 nanoparticles effectively and the preparation process was environmentally friendly.

The Hedgehog (Hh) signaling pathway is critical for embryonic development and tissue renewal. The G protein-coupled receptor (GPCR)-like protein Smoothened (SMO) is the central signal transducer in the Hh pathway. Cholesterol binds and then covalently links to the D95 residue of cysteine-rich domain (CRD) of human SMO. The cholesterylation of CRD is critical for SMO activation. SMO cholesterylation is a Ca2+-boosted autoreaction that requires the formation of an ester bond between the side chains of D95 and Y130 as an intermediate. It is unknown whether other residues of SMO are involved in the esterification between D95 and cholesterol. In this study, we find that the SMO-CRD(27–192) can undergo cholesterylation. In addition to D95 and Y130, the residues critical for cholesterol modification include Y85, T88, T90, W109, W119, K133, E160 and F166. T88, W109, W119 and F166 also seem to be involved in protein folding. Notably, we find that Y85 and K133 form a cation-π interaction whose disruption abolishes cholesterylation and ciliary localization of SMO. This study highlights the mechanism and function of cholesterol modification of SMO.

With the proposal of Industrial Green Development Plan (2016–2020), it is particularly urgent to focus on the industrial green development of oil and gas cities, actively promote industrial energy efficiency, reduce pollution emissions, and measure the efficiency of their industrial green development. Based on the actual situation of oil and gas cities, we apply the Super-SBM model to measure the industrial green development efficiency of oil and gas cities in 15 years from 2004 to 2018, analyze the spatial and temporal evolution trends and characteristics of industrial green development efficiency, and also calculate the Malmquist index to dynamically analyze the industrial green development efficiency of oil and gas cities. The results show that the industrial green development efficiency of oil and gas cities as a whole is not high from 2004 to 2018, showing a gentle “W” type fluctuation change. From the spatial dimension, there are significant differences in industrial green development efficiency among oil and gas cities in the east, central and west, with the efficiency value is relatively higher in the west. The total factor productivity of industrial green development is most influenced by the changes of technical efficiency and technological progress. In view of the above problems, it is recommended to broaden green technology innovation channels, increase green technology innovation investment, build a new mechanism for regional synergistic development, and formulate regional graded development strategies.

Background and ObjectivesThis study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT).MethodsThis cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively.ResultsBefore propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81–2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98–2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12–4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6–18.0 months) and 5.4 months (95% CI: 4.2–8.1 months), respectively (HR 2.62; 95% CI: 1.43–4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05–6.90; p = 0.037].ConclusionBoth TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.

C27H18NO9Zn, triclinic, P1¯$P\overline{1}$ (no. 2), a = 8.4357(10) Å, b = 10.1228(10) Å, c = 13.5186(10) Å, α = 83.830(7)°, β = 10.1228(10)°, γ = 13.5186(10)°, V = 1142.05(19) Å3, Z = 2, Rgt(F) = 0.0665, wRref(F2) = 0.1427, T = 293(2) K.

C40H24N4O9Co, triclinic, P1̄ (no. 2), a = 11.5623(9) Å, b = 11.5732(12) Å, c = 13.4379(11) Å, α = 82.003(8)°, β = 77.597(7)°, γ = 76.048(8)°, V = 1697.1(3) Å3, Z = 2, Rgt(F) = 0.0462, wRref(F2) = 0.1021, T = 293(2) K.

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation mediates genomic instability by inducing transcription-replication conflicts. Strikingly, CDK12-mutant organoids and patient-derived xenografts are sensitive to inhibition or degradation of the paralog kinase, CDK13. We therein establish CDK12 as a bona fide tumor suppressor, mechanistically define how CDK12 inactivation causes genomic instability, and advance a therapeutic strategy for CDK12-mutant mCRPC.

C16H11O10Cd, monoclinic, C2/c (no. 15), a = 26.026(3) Å, b = 6.3807(6) Å, c = 19.738(5) Å, α = 90, β = 98.162(16), γ = 90, V = 3244.5(10) Å3, Z = 8, Rgt(F) = 0.0359, wRref(F2) = 0.0702, T = 293(2) K.