Search

Glioblastoma is one of the most lethal malignant cancers, displaying striking intratumor heterogeneity, with glioblastoma stem cells (GSCs) contributing to tumorigenesis and therapeutic resistance. Pharmacologic modulators of ubiquitin ligases and deubiquitinases are under development for cancer and other diseases. Here, we performed parallel in vitro and in vivo CRISPR/Cas9 knockout screens targeting human ubiquitin E3 ligases and deubiquitinases, revealing the E3 ligase RBBP6 as an essential factor for GSC maintenance. Targeting RBBP6 inhibited GSC proliferation and tumor initiation. Mechanistically, RBBP6 mediated K63-linked ubiquitination of Cleavage and Polyadenylation Specific Factor 3 (CPSF3), which stabilized CPSF3 to regulate alternative polyadenylation events. RBBP6 depletion induced shortening of the 3UTRs of MYC competing-endogenous RNAs to release miR-590-3p from shortened UTRs, thereby decreasing MYC expression. Targeting CPSF3 with a small molecular inhibitor (JTE-607) reduces GSC viability and inhibits in vivo tumor growth. Collectively, RBBP6 maintains high MYC expression in GSCs through regulation of CPSF3-dependent alternative polyadenylation, providing a potential therapeutic paradigm for glioblastoma.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets' immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development. [ABSTRACT FROM AUTHOR]

Anion-exchange membrane fuel cells (AEMFCs) is a promising renewable energy device for hydrogen production. Anion exchange membranes (AEMs), the key component of AEMFCs, is generally needed for excellent dimensional stability and conductivity. Here, we synthesised a variety of AEMs with different number of C–F bonds to enhance the hydrophilic/hydrophobic micro-phase separation structure while maintaining dimensional stability. At 80 °C, the QPBTTP-PEG-10-F 9 shows high OH− conductivity (∼179.02 mS cm−1), excellent dimensional stability (swelling ratio <19 %), and mechanical properties (elongation at break: 37 %, tensile strength: 71 MPa). In addition, QPBTTP-PEG-10-F 9 shows good alkaline stability (conductivity remaining of 92.52 %) in 3 M NaOH solution for 1800 h. The peak power density (PPD) of a single cell assembled with QPBTTP-PEG-10-F 9 can reach 534.79 mW cm−2 with a current density of 951 mA cm−2. [Display omitted] • QPBTTP-PEG-10-F 9 shows high OH− conductivity and excellent dimensional stability. • The PPD of QPBTTP-PEG-10-F 9 is superior to commercial Versogen-A20. • QPBTTP-PEG-10-F 9 shows excellent mechanical properties. • QPBTTP-PEG-10-F 9 shows good alkaline stability in 3 M NaOH solution for 1800 h. [ABSTRACT FROM AUTHOR]

The poly(aryl piperidinium) backbone has outstanding electrical conductivity and chemical stability, which is ideal for the preparation of anion exchange membranes (AEMs). Hence, in this research we prepared a series of high performance AEMs by introducing electron-rich dibenzothiophene (DBT) monomer into poly(aryl piperidinium) polymer backbone. The larger conjugated surface of the DBT monomer and the presence of heteroatoms facilitated intermolecular interactions between the polymers, which induced the generation of highly efficient ion-transport channels within the membranes, as evidenced by atomic force microscopy (AFM) images. The highest molar addition of DBT monomer, QPDBTTP-25 membrane, showed the highest conductivity (190.90 mS cm−1 at 80 °C) while maintaining robust dimensional stability (swelling ratio was 23.66 % at 80 °C). Owing to the advantages of the poly(aryl piperidinium) polymer backbone, the QPDBTTP-25 membrane also exhibited excellent mechanical properties (tensile strength of 53.03 MPa under fully hydrated condition) and durable chemical stability (conductivity retention remained at 93.2% after being immersed in 2 M NaOH solution at 80 °C for 1500 h). The H 2 /O 2 fuel cell test based on QPDBTTP-25 membrane resulted in a peak power density of 384 mW cm−2 at 80 °C. [Display omitted] • Using efficient superacid-catalyzed polymerization to introduce bulky and rigid DBT monomers into polymers. • The DBT monomers with heteroatoms and conjugated surfaces facilitated intermolecular interactions leading to the formation of interconnected ion transport channels. • The poly(aryl piperidinium) backbone containing DBT monomers had robust mechanical properties and excellent chemical stability. • QPDBTTP-25 membrane achieved high conductivity while maintaining acceptable dimensional stability. [ABSTRACT FROM AUTHOR]

Background and Objectives: The current study aimed to explore the effect of nutritional prehabilitation on the clinical prognosis of elderly patients undergoing abdominal cancer surgery., Methods and Study Design: A retrospective study was conducted, where participants were divided into two groups based on whether they received oral nutritional supplementation at the first outpatient visit. The nutritional prehabilitation group (n=41) adopted a nutritional prehabilitation mode (a standard energy intake of 25-30 kcal/kg· d was recommended). While the control group (n=55) received routine care. All patients underwent laparoscopic surgery according to the National Comprehensive Cancer Network (NCCN) guidelines. Changes in nutritional status, complications, psychological status, symptoms, hospitalization days, and expenditures were compared between the two groups., Results: Both groups of patients experienced weight loss. However, the decline in body weight in the prehabilitation group was less than that in the control group (-1.88 vs. -2.56 kg, p < 0.001). In the comparison of nutritional prehabilitation group and control group, significant improvements were observed in the Hospital Anxiety Scale scores (5 vs. 5, p = 0.01) and MD Anderson Symptom Inventory scores (3 vs. 0, p < 0.001) respectively. The infection rate in the nutritional prehabilitation group was lower than that in the control group (17.1% vs. 36.4%, p = 0.04). Additionally, patients in the nutritional prehabilitation group had significantly fewer hospitalization days at discharge (14.3 vs. 17.1 days, p = 0.03)., Conclusions: In elderly patients undergoing abdominal cancer surgery, a nutritional prehabilitation model may help maintain better physical and mental status, reduce infection rates, and shorten hospitalization days., Competing Interests: The authors declare no conflict of interest

Background: Systemic immune-inflammation index (SII) is associated with increased risk in a wide range of illnesses. However, few studies have explored the associations between SII and the risk of malnutrition. Therefore, this study aimed to investigate the association between SII and malnutrition in a nationwide, multicenter, cross-sectional study involving Chinese hospitalized patients., Design: From August 2020 to August 2021, a total of 40,379 hospitalized patients met the inclusion and exclusion criteria. Detailed demographic data, diagnoses, as well as physical and laboratory examination results were recorded. The diagnosis of malnutrition was used with two distinct methods: the Malnutrition Screening Tool 2002 (NRS 2002) + Global Leaders Initiative on Malnutrition (GLIM) criteria and the controlling nutritional status (CONUT) score. The risk factors for malnutrition were analyzed using binary logistic regression and multiple logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). Restricted cubic spline (RCS), linear spline, and receiver operating characteristic (ROC) analysis were also used., Results: The prevalence of malnutrition diagnosed by the two methods was 13.4% and 14.9%, respectively. In the NRS 2002 + GLIM diagnostic model, lnSII showed statistical significance between the malnutrition and non-malnutrition group (6.28 ± 0.78 vs. 6.63 ± 0.97, p < 0.001). A positive association was observed between higher SII and the risk of malnutrition in both before and after adjustment models compared to the first quartile (Q 3 vs. Q 1 , OR = 1.27, 95%CI: 1.15-1.40; Q 4 vs. Q 1 , OR = 1.83, 95%CI: 1.67-2.00). However, a significant reduction in prevalence was observed when SII was in the second quartile (Q 2 vs. Q 1 , OR < 1), as indicated by a restricted cubic spline with a U trend ( p for nonlinear <0.001). According to the CONUT score, the prevalence of individuals with normal nutritional status decreased with increasing SII, while the occurrence of three different degrees of malnutrition generally increased. The Kappa value between the two diagnostic methods was 0.23, and the merged data observed an area under the ROC curve of 0.73 (95%CI: 0.714-0.742)., Conclusion: The U-shaped association between SII and the prevalence of malnutrition was observed. Both lower and higher SII levels (either continuous or categorical variable) were significantly associated with an increased risk of malnutrition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Wang, Yang, Bai, Gu, Luo, Zhang, Han, Shao, Xu, Guo and Ren.)