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Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor–stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases. Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

In recent years, indium-oxide thin-film transistors (IOTFTs) have been developed with high electron mobility, low power consumption, and good environmental stability. A major challenge in current IOTFTs research lies in developing high-performance devices through low-temperature processes while simultaneously expanding their functionality into photonic applications. Our study proposes a low-temperature annealing method for high-performance IOTFTs fabrication, combining substrate heating and a multi-stage annealing process. The optimized device exhibits a device mobility of 47.99 cm2/V·s, a threshold voltage of 2.8 V, a subthreshold swing (SS) of 742.83 mV/dec, and good stability under bias stress tests. Building upon the IOTFTs, we extend the functionality to photonic applications by integrating poly[[2,3,5,6-tetrahydro-2,5-bis(2-octyldodecyl)-3,6-dioxopyrrolo[3,4-c]pyrrole-1,4-diyl]-2,5-thiophenediylthieno[3,2-b]thiophene-2,5-diyl-2,5-thiophenediyl] (DPPDTT) photoresponsive layer, achieving a phototransistor with responsivity of 3.7 A/W and detectivity of 5.86 × 1011 Jones at 850 nm near-infrared light. This work provides a new approach for fabricating high-performance indium-oxide thin-film transistors and phototransistors with low-temperature annealing.

Background Pseudopodium-enriched atypical kinase 1 (PEAK1) expression is altered in multiple human malignancies and promotes tumor proliferation, metastasis, and chemical therapy resistance. Here, we aimed to investigate the role and mechanisms of PEAKs in prostate cancer (PCa) progression and docetaxel resistance. Methods The expression of PEAKs in PCa cells (LNCaP, PC3, DU145, and VCaP) was analyzed. PEAK1 knockdown or overexpression models were established in DU145, LNCaP, and PC3 cells. Functional assays were conducted to measure cell proliferation via CCK-8, EdU staining, and colony formation assays; cell migration was tested via transwell assays; and epithelial-to-mesenchymal transition (EMT) was detected via Western blotting. The sensitivity of PCa cells to docetaxel (DTX) or enzalutamide was tested via the CCK8 assay. A coculture model of PCa cells and THP-1 cells was used to test the interaction between PCa cells and THP-1 macrophages. Furthermore, the effects of PEAK1 on PCa cell growth were investigated in a xenograft model in nude mice. Western blot analysis was used to validate the expression levels of HIF-1α, PD-L1, STAT3, and NF-κB p65. Immunohistochemistry was used to detect infiltration of macrophages and T cells in the tumors. Results PEAK1 expression was significantly elevated in DU145 and PC3 cells after long-term treatment with DTX. PEAK1 upregulation promoted cell proliferation, migration, EMT, and growth in nude mice, whereas PEAK1 knockdown reversed these effects. PEAK1 overexpression attenuated PCa cell sensitivity to DTX and enzalutamide, as evidenced by enhanced cell proliferation and reduced apoptosis. Furthermore, PEAK1-overexpressing PCa cells induced CCL2 and IL-6 production and promoted “M2” polarization of macrophages (M2–Mφ). M2–Mφs enhanced PCa cell proliferation and migration and attenuated DTX sensitivity. In vivo assays revealed that PEAK1 upregulation enhanced PCa cell growth and M2–Mφ infiltration but reduced CD8 +  T -cell infiltration. Mechanistically, TGF- β , possibly produced by “M2” macrophages, induced PEAK1 upregulation. PEAK1 overexpression led to increased expression of HIF-1α and increased STAT3 and NF-κB pathway activation in PCa cells. Conclusions PEAK1 plays an oncogenic role in prostate cancer by promoting cell metastasis, reducing docetaxel and enzalutamide sensitivity, and mediating “M2” polarization of macrophages by activating the HIF-1α/STAT3/NF-κB pathway.

Inflammation accompanies hepatic dysfunction resulting from tissue oxidative damage. Naringenin (Nar), a natural flavanone, has known antioxidant and anti-inflammatory activities, but its mechanism of action in the regulation of liver dysfunction requires further investigation. In this study, the role of naringenin in lipopolysaccharide (LPS)-induced hepatic oxidative stress and inflammation was explored, as well as its mechanism by transcriptome sequencing. The results indicated that compared with the LPS group, Nar treatment caused a significant increase in the mRNA levels of antioxidant factors glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM), yet the expression of related inflammatory factors (MCP1, TNFα, IL-1β and IL-6) showed less of an increase. RNA sequencing identified 36 differentially expressed lncRNAs and 603 differentially expressed mRNAs. KEGG enrichment analysis indicated that oxidative stress and inflammation pathways are meticulously linked with naringenin treatment. The Co-lncRNA-mRNA network was also constructed. Tissue expression profiles showed that lncRNA played a higher role in the liver. Subsequently, expression levels of inflammatory factors indicated that lncRNAs and target mRNAs were significantly reduced after naringenin treatment in mouse liver AML12 cells and obese mouse. These results suggest that naringenin helps to prevent liver dysfunction through the regulation of lncRNA-mRNA axis to reduce oxidative stress and inflammatory factors.

Background Our previous work demonstrated that lncRNA-MALAT1 was overexpressed in recurrent colorectal cancer (CRC) and metastatic sites in post-surgical patients. However, the upstream regulatory mechanism of MALAT1 is not well-defined. Histone demethylase JMJD2C holds great potential of epigenetic regulating mechanism in tumor diseases, especially the moderating effect on the promoter activity of targeted genes associated closely with tumor development. Therefore, we herein investigated whether JMJD2C could epigeneticly regulate the promoter activity of MALAT1 and the downstream β-catenin signaling pathway, thereby affecting the metastatic abilities of CRC cells. Methods JMJD2C expressions in human CRC samples were detected by real-time PCR and immunohistochemistry staining. Gene silencing and overexpressing efficiencies of JMJD2C were confirmed by real-time PCR and western blot. The migration of CRC cells in vitro were tested by transwell and wound healing assays. The protein expression and cellular localization of JMJD2C and β-catenin were characterized by immunofluorescence staining and western blot. The histone methylation level of MALAT1 promoter region (H3K9me3 and H3K36me3) was tested by ChIP-PCR assays. The promoter activity of MALAT1 was detected by luciferase reporter assay. The expressions of MALAT1 and the downstream β-catenin signaling pathway related genes in CRC cells were detected by real-time PCR and western blot, respectively. The nude mice tail vein metastasis model was established to observe the effect of JMJD2C on the lung metastasis of CRC cells in vivo. Results Our present results indicated that histone demethylase JMJD2C was overexpressed in matched CRC tumor tissues of primary and metastatic foci, and CRC patients with lower JMJD2C expression in primary tumors had better prognosis with longer OS (Overall Survival). The following biological function observation suggested that JMJD2C promoted CRC metastasis in vitro and in vivo. Further molecular mechanism investigation demonstrated that JMJD2C protein translocated into the nuclear, lowered the histone methylation level of MALAT1 promoter in the sites of H3K9me3 and H3K36me3, up-regulated the expression of MALAT1, and enhanced the β-catenin signaling pathway in CRC cells. Conclusion Our data demonstrated that JMJD2C could enhance the metastatic abilities of CRC cells in vitro and in vivo by regulating the histone methylation level of MALAT1 promoter, thereby up-regulating the expression of MALAT1 and enhancing the activity of β-catenin signaling pathway, providing that JMJD2C might be a novel therapeutic target for CRC metastasis.

Hemorrhagic fever with renal syndrome (HFRS) is a widespread zoonotic disease transmitted by rodents, posing a serious public health threat in People's Republic of China. Due to the higher incidence of HFRS occurred in Shandong Province, this study aims to understand the spatiotemporal pattern of HFRS, identify the driving factors and predict potential high-risk areas in Shandong Province, to provide guidance for public health policy making. Case information on HFRS occurred in Shandong Province from 2018 to 2024 was collected from the China Information System for Disease Control and Prevention (CISDCP). Incidence rate of HFRS was calculated monthly and annually to explore its preliminary distribution trend. Spatiotemporal scanning analysis was used to determine the temporal and spatial clustering characteristics of HFRS cases. The maximum entropy (MaxEnt) model was employed to explore the major factors influencing HFRS and predict high-risk areas of HFRS in Shandong Province. From 2018 to 2024, a total of 4,837 cases of HFRS were reported in Shandong Province, with the incidence rate showing a fluctuating downward trend. The peak incidence period occurred annually from October to December. Spatiotemporal scanning analysis showed the first cluster involved 29 counties across 5 prefecture-level cities in eastern Shandong Province, spanning October to November 2018. The second cluster involved 16 counties across 6 prefecture-level cities in central Shandong Province, spanning November to December 2021. The third cluster area involved 4 counties across 2 prefecture-level cities in southwestern Shandong Province, spanning March to April 2018. The fourth cluster area was located in Shanghe County, north of Jinan City, spanning November to December 2021. When optimizing the MaxEnt model, the optimal performance was achieved with the feature class (FC) set to linear, quadratic, hinge, product, and threshold (LQHPT) and the regularization multiplier (RM) set to 0.2. Yearly average air temperature, normalized difference vegetation index, yearly average relative humidity and yearly average sunshine duration were identified as the main factors influencing the occurrence of HFRS. The risk prediction map showed that high-risk areas for HFRS were primarily concentrated in the eastern and central regions of Shandong Province, covering an area of 26682.92 square kilometers, accounting for 16.90% of the province's total area. HFRS in Shandong Province exhibited obvious spatiotemporal patterns and was influenced by multiple factors, including temperature, vegetation, humidity and sunshine. These findings highlight the need for health authorities to integrate environmental and socio-economic considerations into the design of strategy or countermeasures against HFRS, particularly during high-incidence season and in high-risk areas.

Displacement monitoring systems play a crucial role in ensuring the safety of tunnels. Existing sensing technologies and analysis methods may be insufficient for monitoring tunnel displacement, particularly vertical displacement, due to the harshness of long-term monitoring conditions and the intricacies of structural characteristics. A long-gauge fiber Bragg grating (FBG) sensor can be used to obtain macro- and micro-level information and be connected in series for area sensing. In this study, a novel method was developed which utilizes long-gauge strain sensors to monitor the vertical displacement of a tunnel. This method employs a combination of mechanical analysis and monitoring data to accurately estimate the vertical displacement of the structure from the measured coupled strain. Several key aspects of the proposed method for identifying vertical displacement were investigated, including establishing a separation model of coupled strain on the cross-section, deriving the theory for vertical displacement identification, and determining the sensor layout of the tunnel. A series of simulation tests of a tunnel with a three-hole frame structure confirmed the efficiency and robustness of the proposed method, even when subjected to various loading conditions, noise levels, and sensor layouts. The results of this work may provide valuable insights and practical guidance for the effective and continuous displacement measurement of tunnels, ensuring their structural integrity and operational safety.

Background Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. Methods A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. Results A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 ( P  < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. Conclusions There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.

Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number of studies indicate that epithelial-to-mesenchymal transition (EMT) plays an important role in CRC metastasis, and our previous studies demonstrate that β-arrestin1could regulate EMT in CRC partly through β-catenin signaling pathway. In this work, we investigate whether Tan IIA could regulate EMT in CRC through β-arrestin1-mediated β-catenin signaling pathway both in vivo and in vitro . Our results showed that Tan IIA inhibited lung metastases of CRC cells in vivo and extended the survival time of mice with CRC. In vitro , Tan IIA increased the expression of E-cadherin, decreased the expression of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression of β-arrestin1 expression, resulting in the increase of GSK-3β expression, reduction of β-catenin nuclear localization, thereby decreased the activity of β-catenin signaling pathway. Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC.

Depression is one of the common incidental symptoms in end-stage renal disease (ESRD) patients, empirically overlooked. Reproducible results observed that altered interregional white matter (WM) connections between depression-related brain regions (thalamus, amygdala, and prefrontal cortex (PFC)) in the human brain were closely associated with depression. Whether the depressive tendency of ESRD patients is also association with the WM connections is remains unknown. To address this problem, 56 ESRD patients before dialysis initiation and 56 healthy controls (HCs) were scanned with diffusion tensor imaging. According to the diagnostic and statistical manual of mental disorders, ESRD patients were separated into with and without depressive tendency groups. Twenty-five essential metabolites were tested in ESRD. The tractography atlas-based analysis and multiple regression analysis were implemented to gain features which could map the depressive tendency variability across ESRD. For metabolites, the levels of thrombocytes and calcium have significant differences between with and without depressive tendency groups. For WM microstructure, depressive tendency ESRD patients had abnormal WM diffusion properties along the fiber tracts of the amygdala-PFC. Compared with the features which were extracted from the group-difference of WM or metabolites, only WM features combinations (1000 bootstrap samples; 5000 permutation tests) along the fiber tract of the amygdala-PFC was a significant predictor of either with or without depressive tendency. Our findings suggested that the advanced neuroprotection may be planned before dialysis initiation, and the WM characteristics of amygdala-PFC may be a potential neuromarkers for the early diagnosis of depressive tendency in ESRD patients before dialysis initiation.