Immunotherapy is known to be a promising strategy in the clinical treatment of malignant tumors, but it has received generally low response rates in various tumors because of the poor immunogenicity ...and multiple immunosuppressive microenvironments. A self-delivery photodynamic re-educator, denoted as CCXB, is synthesized through the self-assembly of chlorine e6 (Ce6) and celecoxib (CXB). As a carrier-free nanomedicine, CCXB shows a high drug loading rate, improved water stability, superior cellular uptake, and tumor accumulation capability. In comparison with free Ce6, CCXB triggers much stronger photodynamic therapy (PDT) to reduce the proliferation of breast cancer cells and activates robust immune responses via the induction of immunogenic cell death (ICD). Better yet, CXB-mediated cyclooxygenase 2 (COX-2) inhibition can decrease the level of synthesis of prostaglandin E2 (PGE2) to further improve immunosuppressive microenvironments. With the increase of cytotoxic T lymphocytes (CTLs) and decrease of regulatory T cells (Tregs) in tumor, in vivo antitumor immunity is significantly amplified to inhibit the metastasis of breast cancer. This study sheds light on developing drug codelivery systems with collaborative mechanisms for immunotherapy of metastatic tumors.
Bimetal oxides are widely used in the field of lithium ion storage because of their high theoretical capacity. However, the capacity of the bimetal oxides decays sharply due to its poor electrical ...conductivity. Herein, a novel oxygen vacancy defect bimetal oxide NiCoO2-x@CNTs composite with carbon nanotubes (CNTs) anchored on defective NiCoO2-x microspheres was prepared toward enhancement of lithium ions storage. The defective NiCoO2-x microsphere improves electrical conductivity and accelerates lithium ion transfer. The microspheres have abundant mesopores to shorten the diffusion path of lithium ions and accommodate volume fluctuation. In additional, CNTs anchored on NiCoO2-x microspheres further enhance structural stability and electrical conductivity. NiCoO2-x@CNT electrodes exhibit excellent electrochemical performance with good rate capability (521.9 mA h g−1 at 5 A g−1) and outstanding long-cycle stability (965 mA h g−1 at 0.1 A g−1 over 155 cycles, 1114.3 mA h g−1 at 0.5 A g−1 over 360 cycles, 618.4 mA h g−1 at 1 A g−1 over 400 cycles and 520 mA h g−1 at 5 A g−1 over 400 cycles) when NiCoO2-x@CNT is employed as a lithium-ion battery anode. This defective material design strategy provides an effective way for improving lithium ion storage.
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Molecular‐sieving membranes from metal–organic frameworks (MOFs) are promising candidates for separating olefin/paraffin mixtures, a critical demand in sustainable chemical processes and a grand ...challenge in molecular separation. Currently, the inherent lattice flexibility of MOFs severely compromises their precise sieving ability. Here, a proof‐of‐concept of “alloy” membranes (AMs), which are fabricated by incorporating quaternary ammonium (QA)‐functionalized covalent organic frameworks (COFs) into a zeolitic imidazolate framework‐8 (ZIF‐8) matrix is demonstrated. The Coulomb force between the COFs and the ZIF‐8 restricts the linker rotation of the ZIF‐8, generating a distinct alloying effect, by which the lattice rigidity of ZIF‐8 can be conveniently tuned through varying the content of the COFs, similar to the flexible‐to‐rigid transition in aluminum alloy manufacturing. Such an alloying effect confers the AM's superior propylene/propane separation performance, with a propylene/propane separation factor surpassing 200 and a propylene permeance of 168 GPU. Hopefully, the AMs concept and the concomitant alloying effect can update the connotation of mixed matrix membranes and stimulate the re‐envisioning about the design paradigm and development of advanced membranes for energy‐efficient separations.
A metal–organic framework (MOF)–covalent organic framework (COF) “alloy” membrane (AM) is fabricated, which exhibits a record‐high propylene/propane separation performance with a selectivity of more than 200 and a propylene permeance of 168 GPU, owing to the fine‐tuned lattice rigidity of the MOF lattice, enabled by a facile, generic alloying strategy.
At present, the control of membrane biofouling is mainly achieved by regulating quorum sensing. In this study, the quorum-sensing inhibitor astragaloside IV was used to prevent membrane biofouling in ...a membrane bioreactor. It was found that astragaloside IV at a concentration of 1 mg/L doubled the time taken for membrane contamination to occur, and decreased the energy required for filtration by 62% without affecting reactor’s processing performance. This is because the addition of astragaloside IV decreased the soluble microbial protein concentration and the loosely bound extracellular polysaccharide content. Biodiversity analysis indicated that astragaloside IV may have inhibited membrane contamination by interfering with the structure of the bacteria community, particularly the populations of quorum-sensing bacteria, bacteria related to extracellular polymeric substance production, and quorum-quenching bacteria. This is the first time the effects of astragaloside IV on membrane contamination in membrane reactors and the inhibition mechanisms involved were investigated. Using astragaloside IV could effectively decrease the energy consumed in operating a membrane bioreactor.
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•Astragaloside IV alleviated membrane biofouling formation in membrane bioreactor.•Astragaloside IV reduced EPS content and the abundance of EPS-producing bacteria.•The abundance of quorum sensing bacteria was reduced by astragaloside IV.•Astragaloside IV increased quorum quenching bacterial abundance in the biocake.•The filtration energy of the astragaloside IV-treated reactor was reduced by 61.9%.
Dysregulation of the Wnt/β-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt pathway inhibitors being studied in preclinical or clinical ...settings for other cancers such as colorectal and pancreatic cancers are either too cytotoxic or insufficiently efficacious for GC. Thus, we screened new potent targets from β-catenin destruction complex associated with GC progression from clinical samples, and found that scaffolding protein RACK1 deficiency plays a significant role in GC progression, but not APC, AXIN, and GSK3β. Then, we identified its upstream regulator UBE2T which promotes GC progression via hyperactivating the Wnt/β-catenin signaling pathway through the ubiquitination and degradation of RACK1 at the lysine K172, K225, and K257 residues independent of an E3 ligase. Indeed, UBE2T protein level is negatively associated with prognosis in GC patients, suggesting that UBE2T is a promising target for GC therapy. Furthermore, we identified a novel UBE2T inhibitor, M435-1279, and suggested that M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1, resulting in suppression of GC progression with lower cytotoxicity in the meantime. Overall, we found that increased UBE2T levels promote GC progression via the ubiquitination of RACK1 and identified a novel potent inhibitor providing a balance between growth inhibition and cytotoxicity as well, which offer a new opportunity for the specific GC patients with aberrant Wnt/β-catenin signaling.
Due to the rapid evolution of antibiotic resistance in
, antivirulence therapy may be a promising alternative for the effective control of the spread of resistant pathogens. The Chinese Materia ...Medica has been widely used for the treatment of diseases and production of health foods, and it remains a valuable resource for the discovery of compounds possessing antivirulence activity. Through a
infection model, an EtOAc-soluble fraction of 80% EtOH extract of
Bunge (SMEA) was found to possess potential anti-infective activity against
. Then, several
assays indicated that SMEA had robust antivirulence activity at the dose of 400 μg mL
, reducing hemolytic activity and α-hemolysin expression in
. Furthermore, at 100 mg kg
, SMEA reduced abscess formation in the main organs of mice challenged with
. In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both
and
. Furthermore, at 24 μg mL
, TNB significantly reduced the expression of
and
, indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. In conclusion, TNB's antivirulence properties make it a promising candidate for drug development against
infections.
When tunnels are constructed at shallow depths in areas with poor geological conditions, such as portal sections, valleys and hillsides in regions with granitic bedrock, considerable ...excavation-induced deformation of the surrounding rock may occur, potentially resulting in tunnel collapses. The main reason for these problems is the lack of understanding of the deformation mechanism and evolution of the soft granitic rock surrounding the tunnel and the adoption of inappropriate construction technology and methods. This article analyzes the deformation mechanism of the rock surrounding a shallow tunnel based on in situ monitoring data as a case study and suggests that certain measures should be taken to effectively control the deformation of the surrounding rock and to minimize the potential for tunnel collapse. The results show that the deformation of the granitic soil surrounding the tunnel can be divided into three stages: the rapid deformation stage, the slow deformation stage and the stabilization stage. Appropriate construction methods should be carefully selected to ensure safety during tunnel excavation in the first stage. To avoid secondary disasters caused by tunnel collapses, three treatment measures may be implemented as part of safety management: enhancing the monitoring of the surrounding rock deformation, adjusting the construction methods and optimizing the support systems. In particular, accurate monitoring data and timely information feedback play a vital role in tunnel construction. Therefore, engineers with considerable engineering experience and professional knowledge are needed to analyze the monitoring data and make accurate predictions of tunnel deformation to ensure that reasonable measures are taken in the process of shallow tunnel excavation.
Background Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death ...(PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method We retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes—CLTCL1, EDIL3, and SQLE—resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion The five genes constituting the OS-PCDS model—CLTCL1, MTM1, MLH1, EDIL3, and SQLE—were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.
No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in ...average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.
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