Gliomas are the most aggressive primary intracranial malignancies with poor overall survival. ITGA5 is one member of the integrin adhesion molecule family and is implicated in cancer metastasis and ...oncogenesis. However, few studies have explored the association between tumor immune microenvironment and ITGA5 expression level in gliomas. Firstly, we analyzed 3,047 glioma patient samples collected from the TCGA, the CGGA, and the GEO databases, proving that high ITGA5 expression positively related to aggressive clinicopathological features and poor survival in glioma patients. Then, based on the ITGA5 level, immunological characteristics and genomic alteration were explored through multiple algorithms. We observed that ITGA5 was involved in pivotal oncological pathways, immune-related processes, and distinct typical genomic alterations in gliomas. Notably, ITGA5 was found to engage in remolding glioma immune infiltration and immune microenvironment, manifested by higher immune cell infiltration when ITGA5 is highly expressed. We also demonstrated a strong correlation between ITGA5 and immune checkpoint molecules that may be beneficial from immune checkpoint blockade strategies. In addition, ITGA5 was found to be a robust and sensitive indicator for plenty of chemotherapy drugs through drug sensitivity prediction. Altogether, our comprehensive analyses deciphered the prognostic, immunological, and therapeutic value of ITGA5 in glioma, thus improving individual and precise therapy for combating gliomas.
X-ray computed tomography (CT) has been widely used in clinical practice, and contrast agents such as Iohexol are often used to enhance the contrast of CT imaging between normal and diseased tissue. ...However, such contrast agents can have some toxicity. Thus, new CT contrast agents are urgently needed. Owing to the high atomic number (
Z
= 83), low cost, good biological safety, and great X-ray attenuation property (5.74 cm
2
kg
−1
at 100 keV), bismuth has gained great interest from researchers in the field of nano-sized CT contrast agents. Here, we synthesized BiF
3
: Ln@PVP nanoparticles (NPs) with an average particle size of about 380 nm. After coating them with polyvinylpyrrolidone (PVP), the BiF
3
: Ln@PVP NPs possessed good stability and great biocompatibility. Meanwhile, compared with the clinical contrast agent Iohexol, BiF
3
: Ln@PVP NPs showed superior in vitro CT imaging contrast. Subsequently, after in situ injection with BiF
3
: Ln@PVP NPs, the CT value of the tumor site after the injection was significantly higher than that before the injection (the CT value of the pre-injection and post-injection was 48.9 HU and 194.58 HU, respectively). The morphology of the gastrointestinal (GI) tract can be clearly observed over time after oral administration of BiF
3
: Ln@PVP NPs. Finally, the BiF
3
: Ln@PVP NPs were completely discharged from the GI tract of mice within 48 h of oral administration with no obvious damage to the GI tract. In summary, our easily synthesized BiF
3
: Ln@PVP NPs can be used as a potential clinical contrast agent and may have broad application prospects in CT imaging.
With the rapid development of intensive mariculture, lots of mariculture wastewaters containing residual feed and excrements are discharged into marinelands, leading to coastal pollution. Recently, ...the environmental problems caused by the discharge of mariculture wastewater have been paid much attention, as have other breeding industries in China. In fact, organic solid waste accounts for most of the pollutants and can be reduced by precipitation or filtration technologies, after which the supernatant can be easily treated by ecological methods. Some national guidelines and relevant local standards have been issued to strictly control the mariculture wastewater, but there are still few effective technologies for mariculture wastewater treatment due to its high salinity and extremely low pollutant concentration. This paper aims to propose feasible pollution control methods of mariculture wastewater according to the wastewater characteristics from different mariculture modes. For raw ammonia-based wastewater, it should be sequentially treated by precipitation, nitrification and denitrification and ecological methods, which would target solid waste, organic carbon/nitrogen and phosphorus removal, respectively. For the nitrate-based wastewater, this just needs denitrification filters and ecological methods for nitrate and phosphorus removal. After an overview of pollution control strategies for different types and scales of industrial mariculture wastewater treatment, some challenges are also mentioned.
Abstract Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could ...hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 ( PIK3R1 ), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chronic inflammation can promote cancer development as observed in inflammation‐induced colorectal cancer (CRC). However, the poor treatment outcomes emphasize the need for effective treatment. ...Astragalus polysaccharide (APS), a vital component of the natural drug Astragalus, has anti-tumor effects by inhibiting cancer cell proliferation and enhancing immune function. In this study, we found that APS effectively suppressed CRC development through activating CD8+ T cells and reversing its inhibitory state in the tumor microenvironment (TME) of AOM/DSS inflammation‐induced CRC mice. Network pharmacology and clinical databases suggested that the STAT3/ Galectin-3(Gal-3)/LAG3 pathway might be APS's potential target for treating CRC and associated with CD8+ T cell dysfunction. In vivo experiments showed that APS significantly reduced phosphorylated STAT3 and Gal-3 levels in tumor cells, as well as LAG3 in CD8+ T cells. Co-culture experiments with MC38 and CD8+ T cells demonstrated that APS decreased the expression of co-inhibitory receptor LAG3 in CD8+ T cells by targeting STAT3/Gal-3 in MC38 cells. Mechanism investigations revealed that APS specifically improved CD8+ T cell function through modulation of the STAT3/Gal-3/LAG3 pathway to inhibit CRC development, providing insights for future clinical development of natural anti-tumor drugs and immunotherapies as a novel strategy combined with immune checkpoint inhibitors (ICIs).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In recent years, with the development of blockchain, electronic bidding auction has received more and more attention. Aiming at the possible problems of privacy leakage in the current electronic ...bidding and auction, this paper proposes an electronic bidding auction system based on blockchain against malicious adversaries, which uses the secure multi-party computation to realize secure bidding auction protocol without any trusted third party. The protocol proposed in this paper is an electronic bidding auction scheme based on the threshold elliptic curve cryptography. It can be implemented without any third party to complete the bidding auction for some malicious behaviors of the participants, which can solve the problem of resisting malicious adversary attacks. The security of the protocol is proved by the real/ideal model paradigm, and the efficiency of the protocol is analyzed. The efficiency of the protocol is verified by simulating experiments, and the protocol has practical value.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A new type of
(BOM) is reported for the first time, by extensively investigating the response dynamics of a one-dimensional (1D) paced excitable system with unidirectional coupling. The BOM state is ...an alternating transition between two distinct phases, i.e., the phase with multiple short spikes and the phase with a long interval. The realizable region and the unrealizable region for the evolution of BOM are identified, which is determined by the initial pulse number in the system. It is revealed that, in the realizable region, the initial inhomogeneous BOM will eventually evolve to the homogeneously distributed
(SOM), while it can maintain in the unrealizable region. Furthermore, several dynamical features of BOM and SOM are theoretically predicted and have been verified in numerical simulations. The mechanisms of the emergence of BOM are discussed in detail. It is revealed that three key factors, i.e., the linking time, the system length, and the local dynamics, can effectively modulate the pattern of BOM. Moreover, the suitable parameter region of the external pacing (
) that can produce the new type of BOM, has been explicitly revealed. These results may facilitate a deeper understanding of bursts in nature and will have a useful impact in related fields.
Offline programming (OLP) is a mainstream approach for controlling assembly robots at construction sites. However, existing methods are tailored to specific assembly tasks and workflows, and thus ...lack flexibility. Additionally, the emerging large language model (LLM)-based OLP cannot effectively handle the code logic of robot programming. Thus, this paper addresses the question: How can robot control programs be generated effectively and accurately for diverse construction assembly tasks using LLM techniques? This paper describes a closed user-on-the-loop control framework for construction assembly robots based on LLM techniques. A hierarchical strategy to generate robot control programs is proposed to logically integrate code generation at high and low levels. Additionally, customized application programming interfaces and a chain of action are combined to enhance the LLM's understanding of assembly action logic. An assembly task set was designed to evaluate the feasibility and reliability of the proposed approach. The results show that the proposed approach (1) is widely applicable to diverse assembly tasks, and (2) can improve the quality of the generated code by decreasing the number of errors. Our approach facilitates the automation of construction assembly tasks by simplifying the robot control process.
•A closed user-on-the-loop construction assembly robot control framework based on LLM techniques is developed.•A hierarchical robot control program generation strategy is proposed.•Customized APIs and Chain of Action are combined to enhance LLM's understanding of assembly action logic.•The proposed approach is widely applicable to diverse assembly tasks.•The proposed approach can improve the quality of generated code by decreasing the number of errors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Here, we report the application of a computational approach that allows the rational design of enzymes with enhanced thermostability while retaining full enzymatic activity. The approach is based on ...the optimization of the energy of charge-charge interactions on the protein surface. We experimentally tested the validity of the approach on 2 human enzymes, acylphosphatase (AcPh) and Cdc42 GTPase, that differ in size (98 vs. 198-aa residues, respectively) and tertiary structure. We show that the designed proteins are significantly more stable than the corresponding WT proteins. The increase in stability is not accompanied by significant changes in structure, oligomerization state, or, most importantly, activity of the designed AcPh or Cdc42. This success of the design methodology suggests that it can be universally applied to other enzymes, on its own or in combination with the other strategies based on redesign of the interactions in the protein core.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential ...therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)‐induced damage to human neuroblastoma cell line, SH‐SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co‐culture with hDPSCs by transwell co‐culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs‐treated cells were found to restore gradually with re‐elongation of retracted dendrites. Meanwhile, Cell Counting Kit‐8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs‐treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α‐tubulin and F‐actin demonstrated that the hDPSCs‐treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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