Search

AbstractTo address the critical issue of particulate matter emitted from mining operations, which poses a significant risk to human health, production safety, and the environment, a novel dust suppressant based on xanthan gum (XTG) as a coalescing agent was introduced in this study. The formulation innovatively combines anionic surfactants SDS (Sodium dodecyl sulfate) and SDBS (Sodium dodecyl benzene sulfonate) as well as nonionic surfactants OP-10, Tween-20 (Polyoxyethylene anhydrous sorbitan monolaurate) and Tween-80 (Polyoxyethylene anhydrous sorbitan monooleate) with 0.05% XTG to enhance the wettability of the solution. Considering the economy and practicality, 0.05% OP-10 + 0.05% XTG (M-OX) was finally selected as the optimal dust suppressant formulation. Through a series of experiments, including surface tension, contact angle, sedimentation, pH value, water retention, and wind erosion resistance tests, we proved that M-OX, with a pH value of 8.03, has the least impact on the environment, has better water retention, and has a significant dust suppression effect. The curing layer formed by M-OX can adapt to complex weather, maintains its integrity after rain and wind erosion, and exhibits excellent rain and wind erosion resistance. This study provides an environmentally friendly and effective dust suppression solution for surface coal mines with significant social and economic benefits. [ABSTRACT FROM AUTHOR] more...

PANoptosis is a newly identified programmed cell death pathway that integrates characteristics of apoptosis, pyroptosis, and necroptosis. It plays a dual role in the host immune response to bacterial infections. On one hand, PANoptosis acts as a protective mechanism by inducing the death of infected cells to eliminate pathogens and releasing pro-inflammatory cytokines to amplify the immune response. On the other hand, bacteria can exploit PANoptosis to evade host immune defenses. This dual nature underscores the potential of PANoptosis as a target for developing novel therapies against bacterial infections. This review summarizes the molecular mechanisms of PANoptosis, along with the crosstalk and integration of different cell death pathways in response to various bacterial pathogens. We also discuss the dual roles of PANoptosis in bacterial infectious diseases, including sepsis, pulmonary infections, and intestinal infections. Elucidating the molecular mechanisms underlying PANoptosis and how bacteria manipulate this pathway offers critical insights into host–pathogen interactions. These insights provide a foundation for designing targeted antibacterial strategies, modulating inflammation, and advancing precision medicine to improve clinical outcomes. [ABSTRACT FROM AUTHOR] more...

Highlights: SERPINE1 mediates the transfer of cancer-derived exosomal let-7 g-5p to promote macrophage M2 polarization. Exosomal let-7 g-5p drives M2 polarization by downregulating SOCS7 and relieving its inhibition of STAT3 phosphorylation. SERPINE1 promotes the transcription of let-7 g-5p by activating the JAK2/STAT3 signaling pathway.Background: Tumor-associated macrophages (TAMs), particularly M2-polarized TAMs, are significant contributors to tumor progression, immune evasion, and therapy resistance in gastric cancer (GC). Despite efforts to target TAM recruitment or depletion, clinical efficacy remains limited. Consequently, the identification of targets that specifically inhibit or reprogram M2-polarized TAMs presents a promising therapeutic strategy. Objective: This study aims to identify a dual-function target in GC cells that drives both malignant phenotypes and M2 macrophage polarization, revealing its molecular mechanisms to provide novel therapeutic targets for selectivly targeting M2-polarized TAMs in GC. Methods: Transcriptomic and clinical data from GC and adjacent tissues were utilized to identify mRNAs associated with high M2 macrophage infiltration and poor prognosis. Single-cell sequencing elucidated cell types expressing the target gene. Transwell co-culture and exosome intervention experiments demonstrated its role in M2 polarization. Small RNA sequencing of exosomes, western blotting, and CoIP assays revealed the molecular mechanisms underlying exosome-mediated M2 polarization. Protein array, ChIP and dual-luciferase reporter assays clarified the molecular mechanisms by which the target gene regulated exosomal miRNA. In vivo validation was performed using xenograft tumor models. Results: SERPINE1 was identified as a highly expressed mRNA in GC tissues and cells, significantly associated with advanced clinical stages, worse prognosis, and higher M2 macrophage infiltration in patients with GC. SERPINE1 overexpression in GC cells promoted tumor growth and M2 macrophage polarization. SERPINE1 facilitated the transfer of let-7 g-5p to macrophages via cancer-derived exosomes, inducing M2 polarization. Exosomal let-7 g-5p internalized by macrophages downregulated SOCS7 protein levels, disrupting its interaction with STAT3 and relieving the inhibition of STAT3 phosphorylation, thereby leading to STAT3 hyperactivation, which consequently drove M2 polarization. Additionally, in GC cells, elevated SERPINE1 expression activated JAK2, enhancing STAT3 binding to the let-7 g-5p promoter and promoting its transcription, thereby increasing let-7 g-5p levels in exosomes. Conclusion: GC cell-derived SERPINE1, functioning as a primary driver of GC growth and TAM M2 polarization, promotes M2 polarization through the regulation of exosomal let-7 g-5p transfer via autocrine activation of the JAK2/STAT3 signaling pathway. These findings elucidate a novel mechanism of SERPINE1-induced M2 polarization and highlight SERPINE1 as a promising target for advancing immunotherapy and targeted treatments in GC. [ABSTRACT FROM AUTHOR] more...

Francois Jullien suggests that the tradition of indirect writing (I'ecriture indirecte) exists both in China and the West. In China, the tradition of Bi-Xing ( explicit comparison and implicit comparison) originated from The Book of Songs forms the indirect way of expressing emotion in poetry. Such way of expression combined with other original categories of Chinese poetics contributes to the "alterity" of the Chinese literary tradition by creating an "allusivity" in the text. Its Western counterpart is found in symbolism, which nevertheless showcases the heterogeneity between traditional Chinese and Western poetics. Chinese lexical equivalent to "indirect writing" is wanyan (indirect words), a concept rooted in the tradition of Bi-Xing, especially Xing. This essay proposes that Bi-Xing and symbolism are two original parallel concepts in Chinese and Western poetic traditions, between which a Sino-Western dialogue on poetic discourses is made possible. [ABSTRACT FROM AUTHOR] more...

The ubiquitin-proteasome system is a fundamental regulatory mechanism that governs protein stability and intracellular signaling in eukaryotic cells. This system relies on a coordinated cascade of enzymatic activities involving activating enzymes, conjugating enzymes, and ligases to assemble distinct ubiquitin signals. These signals are subsequently edited, removed, or interpreted by deubiquitinases and ubiquitin-binding proteins. While E3 ligases have traditionally been recognized as the primary determinants of substrate specificity in the ubiquitination process, recent studies have revealed that the dysregulation of E2 enzymes can also lead to significant pathological outcomes, including chromatin instability, immune dysregulation, metabolic dysfunction, and an elevated risk of cancer. Consequently, E2 enzymes have emerged as promising therapeutic targets for the treatment of various dis-eases. This review provides a comprehensive examination of the roles and mechanisms of the ubiquitin-conjugating enzyme E2T (UBE2T) in cancer initiation, progression, and therapy resistance, highlighting its potential as a compelling target for cancer therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) more...

The KRAS G12D inhibitor MRTX1133 shows the potential to revolutionize the treatment paradigm for pancreatic ductal adenocarcinoma (PDAC), yet presents challenges. Our findings indicate that KRAS G12D remodels a pentose phosphate pathway (PPP)-dominant central carbon metabolism pattern, facilitating malignant progression and resistance to MRTX1133 in PDAC. Mechanistically, KRAS G12D drives excessive degradation of p53 and glucose-6-phosphate dehydrogenase (G6PD)-mediated PPP reprogramming through retinoblastoma (Rb)/E2F1/p53 axis-regulated feedback loops that amplify ubiquitin-conjugating enzyme E2T (UBE2T) transcription. Genetic ablation or pharmacological inhibition of UBE2T significantly suppresses PDAC progression and potentiates MRTX1133 efficacy. Leveraging structure advantages of the UBE2T inhibitor pentagalloylglucose (PGG), we develop a self-assembling nano co-delivery system with F-127, PGG, and MRTX1133. This system enhances the efficacy of PGG and MRTX1133, achieving durable remissions (85% overall response rate) and long-term survival (100% progression-free survival) in patient-derived xenografts and spontaneous PDAC mice. This study reveals the role of KRAS G12D -preferred PPP reprogramming in MRTX1133 resistance and proposes a potentially therapeutic strategy for KRAS G12D -mutated PDAC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.) more...

Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) more...

Primary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas could help develop effective treatment strategies. Here, we identified a link between Shc1-binding protein (SHCBP1) and cilia in ductal carcinomas. Shcbp1 knockout in transgenic mice profoundly impeded tumor progression and metastasis, prolonging survival. Single-cell transcriptome analysis revealed a functional connection between SHCBP1 deficiency and increased tumor ciliogenesis. SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant (MBR) and centrosome through enhanced Rab8 GTPase activity and Rab8GTP positioning within the MBR. Inhibition of tumor progression by SHCBP1 loss relied on the recovery of ciliogenesis. Analysis of a large cohort of patients with ductal carcinoma revealed a negative correlation between SHCBP1-induced ciliary loss and patient prognosis. Restoring ciliogenesis via SHCBP1 ablation elicited therapeutic effects in patient-derived xenograft models. Together, this study delineates that induction of MBR-centrosome proximity through SHCBP1-deficiency reactivates ciliogenesis, offering unique opportunities for the treatment of unciliated ductal carcinomas. Significance: SHCBP1 depletion rescues tumor ciliogenesis by enhancing Rab8 GTPase activity to restore the proximity of the  midbody remnant to the centrosome, which impedes progression of ductal carcinomas and suggests potential therapeutic strategies., (©2024 American Association for Cancer Research.) more...

Background: Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2 , a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression., Methods: Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2 -associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC., Results: NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro . NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models., Conclusions: Collectively, NUF2 -mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.) more...

Tumors of the digestive system are currently one of the leading causes of cancer-related death worldwide. Despite considerable progress in tumor immunotherapy, the prognosis for most patients remains poor. In the tumor microenvironment (TME), tumor cells attain immune escape through immune editing and acquire immune tolerance. The mevalonate pathway and autophagy play important roles in cancer biology, antitumor immunity, and regulation of the TME. In addition, there is metabolic crosstalk between the two pathways. However, their role in promoting immune tolerance in digestive system tumors has not previously been summarized. Therefore, this review focuses on the cancer biology of the mevalonate pathway and autophagy, the regulation of the TME, metabolic crosstalk between the pathways, and the evaluation of their efficacy as targeted inhibitors in clinical tumor immunotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) more...

Changes in nuclear morphology are common in malignant tumors, but the underlying molecular mechanisms remain poorly understood. Lamins is involved in supporting nuclear structure, and the expression of Lamins is the molecular basis for nuclear morphological changes during tumor progression. In recent years, the research on the relationship between Lamins and malignant tumors has made great progress. Lamins is of great value in the diagnosis, treatment, and prognosis of various malignant tumors. more...