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Hot spot gene mutations in splicing factor 3b subunit 1 (SF3B1) are observed in many types of cancer and create abundant aberrant mRNA splicing, which is profoundly implicated in tumorigenesis. Here, we identified that the SF3B1 K700E (SF3B1K700E) mutation is strongly associated with tumor growth in pancreatic ductal adenocarcinoma (PDAC). Knockdown of SF3B1 significantly retarded cell proliferation and tumor growth in a cell line (Panc05.04) with the SF3B1K700E mutation. However, SF3B1 knockdown had no notable effect on cell proliferation in two cell lines (BxPC3 and AsPC1) carrying wild‐type SF3B1. Ectopic expression of SF3B1K700E but not SF3B1WT in SF3B1‐knockout Panc05.04 cells largely restored the inhibitory role induced by SF3B1 knockdown. Introduction of the SF3B1K700E mutation in BxPC3 and AsPC1 cells also boosted cell proliferation. Gene set enrichment analysis demonstrated a close correlation between SF3B1 mutation and aerobic glycolysis. Functional analyses showed that the SF3B1K700E mutation promoted tumor glycolysis, as evidenced by glucose consumption, lactate release, and extracellular acidification rate. Mechanistically, the SF3B1 mutation promoted the aberrant splicing of PPP2R5A and led to the activation of the glycolytic regulator c‐Myc via post‐translational regulation. Pharmacological activation of PP2A with FTY‐720 markedly compromised the growth advantage induced by the SF3B1K700E mutation in vitro and in vivo. Taken together, our data suggest a novel function for SF3B1 mutation in the Warburg effect, and this finding may offer a potential therapeutic strategy against PDAC with the SF3B1K700E mutation. SF3B1 mutations have been previously implicated in tumorigenesis. Here, we investigate the role of SF3B1K700E mutation in pancreatic ductal adenocarcinoma (PDAC). SF3B1K700E led to aberrant splicing of PPP2R5A, coupled with c‐Myc activation higher aerobic glycolysis rate and growth advantage of tumor cells. Taken together, our data describe a novel function for SF3B1 K700E mutations in the Warburg effect. Inhibition of SF3B1 K700E mutation may potentially serve as a novel therapeutic strategy for patients with PDAC.

Due to the therapy resistance and frequent metastasis, pancreatic ductal adenocarcinoma(PDAC) remains one of the most malignant carcinoma. WNT7A, an important ligand of Wnt/β-catenin signaling pathways, has a controversial role in tumor development. The role of WNT7A in PDAC remains unclear. In this study, we analyzed the expression pattern of WNT7A at mRNA and protein levels. We found pancreatic cancer tissue demonstrated a significant high WNT7A expression compared with the adjacent non-tumor tissue and the expression of WNT7A positively correlates with poor prognosis and lymph node metastasis. Then, we performed transwell assays and wound healing assays in vitro and found that WNT7A promotes the migration capacity of cancer cells. Furthermore, we explored the underlying mechanism of the WNT7A inducing cell migration. Results showed that up-regulated WNT7A expression inducing higher expression of N-cadherin and lower expression of E-cadherin while the contrast result was shown in the WNT7A knock-down group, which suggested that WNT7A might contribute to an epithelial–mesenchymal transition. Finally, we found that the hypoxia culture condition remarkably increased the WNT7A expression. In conclusion, our work demonstrated that hypoxia induced high expression of WNT7A might promote the cell migration via enhancing the epithelial–mesenchymal transition in PDAC.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.

Silver nanoparticles (AgNPs) are recognized for their strong antibacterial properties, particularly in applications such as wound and burn treatment; however, the mechanisms of AgNP‐induced cytotoxicity remain  inadequately defined. This study investigates the role of lysosomal dysfunction in AgNP‐induced cytotoxicity, focusing on lysosomal perinuclear clustering (LPC) and its relationship with cellular apoptosis. Human fibroblast HS27 cells are treated with 24 µg mL−1 AgNPs over 48 h, and lysosomal dynamics, cellular localization, and apoptosis rates are analyzed through confocal microscopy and flow cytometry. Protein expression levels of charged multivesicular body protein 4B(CHMP4B) and Kinesin 1, which are central to lysosomal transport and membrane repair, are examined via western blotting. The findings reveal that AgNP exposure leads to LPC and an increase in apoptosis in a time‐dependent manner, accompanied by reduced Kinesin 1 expression. Further, inhibition of CHMP4B and Kinesin 1 significantly promoted apoptosis, while their overexpression mitigated AgNP‐induced cytotoxic effects, underscoring their essential roles in lysosomal integrity. This study provides new insights into the cellular pathways of AgNP‐induced cytotoxicity, focusing on lysosomal transport disruption, and suggests potential molecular targets to reduce adverse effects in therapeutic applications. These results lay a foundation for optimizing AgNP efficacy and improving their safety profile in clinical settings. AgNPs cause significant damage upon entering the lysosomes of human fibroblasts, resulting in lysosomal transport disorders and the occurrence of perinuclear clustering (LPC) of lysosomes by promoting apoptosis that is accompanied by a reduction in the expression levels of ESCRT III and Kinesin 1 proteins.

Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework.

Hybrid core–shell nanodiamond-gold nanoparticles were synthesized and characterized as a novel multifunctional material with tunable and tailored properties for multifunctional biomedical applications. The combination of nanostructured gold and nanodiamond properties afford new options for optical labeling, imaging, sensing, and drug delivery, as well as targeted treatment. ND@Au core–shell nanoparticles composed of nanodiamond (ND) core doped with Si vacancies (SiV) and Au shell were synthesized and characterized in terms of their biomedical applications. Several bioimaging modalities based on the combination of optical and spectroscopic properties of the hybrid nano-systems are demonstrated in cellular and developing zebrafish larvae models. The ND@Au nanoparticles exhibit isolated ND’s Raman signal of sp 3 bonded carbon, one-photon fluorescence of SiV with strong zero-phonon line at 740 nm, two-photon excited fluorescence of nanogold with short fluorescence lifetime and strong absorption of X-ray irradiation render them possible imaging agent for Raman mapping, Fluorescence imaging, two-photon Fluorescence Lifetime Imaging (TP-FLIM) and high-resolution hard-X-ray microscopy in biosystems. Potential combination of the imaging facilities with other theranostic functionalities is discussed.

BackgroundSeasonal freeze‒thaw (FT) processes alter soil formation and cause changes in soil microbial communities, which regulate the decomposition of organic matter in alpine ecosystems. Soil aggregates are basic structural units and play a critical role in microbial habitation. However, the impact of seasonal FT processes on the distribution of microbial communities associated with soil pores in different aggregate fractions under climate change has been overlooked. In this study, we sampled soil aggregates from two typical alpine ecosystems (alpine meadow and alpine shrubland) during the seasonal FT processes (UFP: unstable freezing period, SFP: stable frozen period, UTP: unstable thawing period and STP: stable thawed period). The phospholipid fatty acid (PLFA) method was used to determine the biomass of living microbes in different aggregate fractions.ResultsThe microbial biomass of 0.25–2 mm and 0.053–0.25 mm aggregates did not change significantly during the seasonal FT process while the microbial biomass of > 2 mm aggregates presented a significant difference between the STP and UTP. Bacterial communities dominated the microbes in aggregates, accounting for over 80% of the total PLFAs. The microbial communities of soil aggregates in the surface layer were more sensitive to the seasonal FT process than those in other soil layers. In the thawing period, Gram positive bacteria (GP) was more dominant. In the freezing period, the ratio of Gram-positive to Gram-negative bacterial PLFAs (GP/GN) was low because the enrichment of plant litter facilitated the formation of organic matter. In the freezing process, pores of 30–80 μm (mesopores) favored the habitation of fungal and actinobacterial communities while total PLFAs and bacterial PLFAs were negatively correlated with mesopores in the thawing process.ConclusionsThe freezing process caused a greater variability in microbial biomass of different aggregate fractions. The thawing process increased the differences in microbial biomass among soil horizons. Mesopores of aggregates supported the habitation of actinobacterial and fungal communities while they were not conducive to bacterial growth. These findings provide a further comprehension of biodiversity and accurate estimation of global carbon cycle.

The powerful capability of reconfigurable intelligent surfaces (RISs) in tailoring electromagnetic waves and fields has put them under the spotlight in wireless communications. However, the current designs are criticized due to their poor frequency selectivity, which hinders their applications in real-world scenarios where the spectrum is becoming increasingly congested. Here we propose a filtering RIS to feature sharp frequency-selecting and 2-bit phase-shifting properties. It permits the signals in a narrow bandwidth to transmit but rejects the out-of-band ones; meanwhile, the phase of the transmitted signals can be digitally controlled, enabling flexible manipulations of signal propagations. A prototype is designed, fabricated, and measured, and its high quality factor and phase-shifting characteristics are validated by scattering parameters and beam-steering phenomena. Further, we conduct a wireless communication experiment to illustrate the intriguing functions of the RIS. The filtering behavior enables the RIS to perform wireless signal manipulations with anti-interference ability, thus showing big potential to advance the development of next-generation wireless communications. A filtering reconfigurable intelligent surface is presented with sharp frequency-selecting and 2-bit phase-shifting properties, offering to advance the development of wireless communications with anti-interference and signal-manipulation abilities.

Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts ( n  = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival ( P  < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632–0.850]), progression-free survival ( P  = 0.002, HR = 0.669 [95% CI: 0.518–0.864]), durable clinical benefit ( P  < 0.001, 54.1% vs. 32.6%), and objective response rate ( P  < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a “hot tumor” phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.

Objectives To compare the effectiveness of vacuum‐assisted closure (VAC) against traditional drainage technique, using a retrospective case‐control study design, in terms of managing deep neck infections (DNIs). Methods Patients presenting to Peking Union Medical College Hospital diagnosed with DNIs were recruited in this study. We analyzed the clinical characteristics of DNI patients and divided them into (a) VAC placement group (26 cases) and (b) traditional drainage group (57 cases) according to whether VAC was placed. The differences in length of stay (LOS), wound healing time, and debridement frequency were compared between the two groups. Results Eighty‐three patients had multiple‐space infections, i.e. infection at two or more sites. The debridement frequency of the VAC group was significantly lower than that of the traditional drainage group (p = 0.001). The wound healing time of the traditional drainage group and VAC group was 38 days (a range of 13–98 days) and 40 days (a range of 11–106 days), respectively; the average LOS was 15 days (a range of 2–68 days) and 16 days (a range of 4–35 days), respectively; and the debridement frequencies were one time (a range of 0–3 times) and zero times (a range of 0–2 times), respectively. The two groups did not differ significantly in wound healing time and hospitalization duration (p = 0.319 and 0.937). Conclusions VAC treatment of DNIs has significant advantages in reducing the frequency of debridement and patient suffering, but it does not show significant advantages in wound healing. Randomized trials are still needed to demonstrate its efficacy. Key Points Deep neck space infections (DNIs) are potentially life‐threatening conditions, which require consistent wound care during relatively long periods of hospitalization. When comparing with the conventional surgical intervention, vacuum‐assisted closure placement in DNIs lowers the frequency of debridement significantly, though little does it contribute to the shortening of wound healing time and hospitalization. Streptococcus pharyngitis is the most common pathogen isolated from the drainage in both groups.