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Podocalyxin-like protein (PODXL) is known to originate from tumor cells in several cancers; however, which cell type it is expressed in, whether and how it may contribute to tumor progression after radiotherapy or chemoradiotherapy in cervical cancer (CC) remain unknown. In this study, we investigated these issues using a cohort of 180 immune stain data, single-cell RNA sequencing (scRNA-seq) data of 29,453 cells, and bulk RNA sequencing data from 187 cervical cancer samples treated with radiotherapy or chemoradiotherapy. ScRNA-seq analysis revealed that PODXL was predominantly expressed in tumor endothelial cells (TECs) of CC, which was corroborated by tumor section staining. Moreover, the PODXL expression level was negatively associated with progression-free survival and overall survival of 180 CC patients receiving radiotherapy or chemoradiotherapy (both p < 0.001). Furthermore, compared with PODXLlow TECs, PODXLhigh TECs exhibited a diminished anti-tumor immune response and enhanced tumor-promoting features characteristics. In addition, PODXL over-expression was also found to be negatively associated with immune response and indicated poor survival in bulk RNA sequencing data of CC treated with radiotherapy or chemoradiotherapy. These results underscore the role of PODXL in CC, suggesting it as a promising target and prognostic marker for patients treated with radiotherapy or chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage–CD90.2+NK1.1–NKp46–ST2–KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence. TCF1 and TOX have been shown to be important in T memory cell formation. Here the authors show that TCF1 and TOX contribute to the regulation and persistence of memory-like ILC2 cells in mouse asthma models and persons with asthma. [ABSTRACT FROM AUTHOR]

Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis, a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments. Deletion of hmwC, encoding a putative OGT, structurally distinct from any existing member of the GT41 family, results in reduced O-GlcNAcylation, reduced growth, and alterations in virulence properties and survival under stress. Purified HmwC can modify target proteins in vitro using UDP-GlcNAc as sugar donor. One of the target proteins, OsdY, promotes Y. pestis survival under oxidative stress conditions. Thus, our results support that regulation of antioxidative responses through O-GlcNAcylation may be a conserved process shared by prokaryotes and eukaryotes. Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is associated with stress responses in eukaryotes. Here, the authors identify a protein that acts as an O-GlcNAc transferase for modification of multiple proteins and regulates antioxidative stress responses in the bacterial pathogen Yersinia pestis. [ABSTRACT FROM AUTHOR]

Background: Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis. However, inhibitors in complex samples such as soil and animal tissues often hamper nucleic acid detection, leading to a reduced rate of identifying low concentrations of Y. pestis. To address this challenge, we developed a sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay for detecting Y. pestis DNA from soil and animal tissue samples. Methods: Three genes (ypo2088, caf1, and pla) from Y. pestis were used to develop a multi-target ddPCR assay. The limits of detection (LoD), reproducibility, and specificity were assessed for bacterial genomic DNA samples. The ability of the assay to detect low concentrations of Y. pestis DNA from simulated soil and mouse liver tissue samples was respectively evaluated and compared with that of quantitative real-time PCR (qPCR). Results: The results showed that the ddPCR LoDs ranged from 6.2 to 15.4 copies/reaction for the target genes, with good reproducibility and high specificity for Y. pestis. By testing 130 soil and mouse liver tissue samples spiked with Y. pestis, the ddPCR assay exhibited a better sensitivity than that of the qPCR assay used in the study, with LoDs of 102 colony forming units (CFU)/100 mg soil and 103 CFU/20 mg liver. Moreover, the assay presented good quantitative linearity (R2 = 0.99) for Y. pestis at 103–106 CFU/sample for soil and liver samples. Conclusion: The ddPCR assay presented good performance for detecting Y. pestis DNA from soil and mouse tissue samples, showing great potential for improving the detection rate of low concentrations of Y. pestis in plague surveillance and facilitating the early diagnosis of plague cases. Author summary: Yersinia pestis is the causative agent of three historic plague pandemics. Presently, the plague remains endemic or sporadic in many countries. The wide distribution of natural plague foci in Asia, Africa, and the Americas reminds us of the threat of a plague outbreak. The timely detection and surveillance of Y. pestis prevalence in animals and the environment in natural epidemic foci is essential for preventing and controlling plague outbreaks. In this study, we developed a sensitive and specific ddPCR assay for detecting low concentrations of Y. pestis DNA from soil and mouse tissue samples. The ddPCR assay presented a considerable improvement in sensitivity compared to the qPCR assay used in the study, thus providing a promising tool for detecting Y. pestis DNA from complex samples and facilitating the accurate diagnosis of plague cases. [ABSTRACT FROM AUTHOR]

Objective To prepare a sheath with variable diameter which can achieve catheterization with small diameter while operation with large diameter, and evaluate its effect of catheterization in animals. Methods With reference to ureter data, a new sheath was designed and made by computer-aided procedure. Then 12 female Chinese pigs were randomly divided into experimental group (new sheath) and control group (12Fr conventional sheath) to undergo sheath insertion and extraction experiments. The time of tube extubation and catheterization, total time of operation, sheath diameter during catheterization, success rate of catheterization, and morphology of ureteral injury were observed and recorded, and the results were compared between the 2 groups. Results The water-balloon ureteral access sheath was successfully prepared. The experimental group had significantly shorter insertion time (1.58±0.41 vs 3.53±1.09 min) and total operation time (9.59±2.95 vs 13.74±3.72 min), smaller outer diameter of sheath during catheterization (2.15±0.25 vs 4.00±0.08 mm), higher catheter success rate (100% vs 80%), and milder ureteral injury when compared with the control group (P < 0.05). But, there were no obvious differences in extraction time and inner diameter after catheterization between the 2 groups (P>0.05). Conclusion Our newly-designed sheath can establish the similar operation channel as the conventional sheath, with the advantages of smaller outer diameter, shorter operation time and milder ureter damage, and has a favorable application prospect.

Objective To observe the effects of the proteasome inhibitor bortezomib (BTZ) on the apoptosis of murine alloreactive T cells in vitro. Methods In a one-way mixed lymphocyte culture system, the T lymphocytes from C57BL/6 mice were co-cultured with the splenocytes of BALB/c mice for 24 h. After treatment of the cells with different concentrations of bortezomib for 12 h, the changes in the cell proliferation were assessed using CCK-8 assay. The responses of the co-cultured cells to different culture times and a 12 h treatment with 0.01 μmol/L bortezomib were examined by detecting the changes in the cell apoptosis, cell cycle and expression of the activation-associated markers CD25 and CD69 using flow cytometry; the expression of cleaved caspase-3 and cyclin D1 was detected using Western blotting, and the levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA). Results Compared with the control cells, the bortezomib-treated T cells showed an obviously decreased proliferative activity. Treatment with 0.01 μmol/L bortezomib significantly increased the percentage of apoptotic T cells and enhanced the expression of cleaved caspase-3 in positive correlation with the co-culture time prior to bortezomib treatment (P < 0.05). The proportion of T cells at G1 phase increased and the expression of cyclin D1 decreased significantly in bortezomib-treated cells (P < 0.05), which also showed down-regulated expressions of CD25 and CD69 and lowered levels of IL-4, TNF-α and IFN-γ in the supernatant (P < 0.05). Conclusion Bortezomib can inhibit the proliferation of murine alloreactive T cells in vitro, induce apoptosis and reduce cytokine production in the activated T cells.

Purpose: Bibliometric analysis has been widely adopted to measure individual productivity and discipline development. This study aims to advance the application of this method in the social work discipline. Method: Using the knowledge mapping technique in CiteSpace 5.8.R3, this study performed a co-word analysis of 1,007 first-authored articles published from 2000 to 2022 by 60 scholars who are listed among the top 2% most-cited scholars on social work and are holding doctoral degrees in the same field. Results: The cluster analysis identified seven main research hotspots and burst detection results revealed four groups of research frontiers, including spiritual and cultural needs, children's wellbeing, social work practices and development, and social work research, with bullying and peer victimization, particularly among African-American adolescents and youth in Chicago's southside, continuing to attract much research interest. Discussion: This study examines how individual works contribute to the conceptual structure and scientific evolution of social work. [ABSTRACT FROM AUTHOR]

Purpose: Using situational leadership theory, this study examined the innovation of social workers in community-level social work institutions under different leadership styles. Methods: We conducted an online survey experiment on the professional strengths of social workers in eight cities of mainland China from December 8–20, 2020. Results: Both ethical leadership and servant leadership are conducive to social workers' innovative behaviors. Our full model also suggests that organizational climate moderates the effects of leadership styles on innovative behaviors, with servant leadership having a greater impact than ethical leadership on social workers' innovative behavior in low-innovation climate environments, but ethical leadership has a greater impact than servant leadership on social workers' innovative behavior in high-innovation climate environments. Conclusion: Our study provides important strategies to fully stimulate the innovation effects of leadership based on the stage characteristics of social work innovation practices. [ABSTRACT FROM AUTHOR]