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Tumor metastasis is a major contributor to the death of cancer patients. It is driven not only by the intrinsic alterations in tumor cells, but also by the implicated cross-talk between cancer cells and their altered microenvironment components. Tumor-associated macrophages (TAMs) are the key cells that create an immunosuppressive tumor microenvironment (TME) by producing cytokines, chemokines, growth factors, and triggering the inhibitory immune checkpoint proteins release in T cells. In doing so, TAMs exhibit important functions in facilitating a metastatic cascade of cancer cells and, meanwhile, provide multiple targets of certain checkpoint blockade immunotherapies for opposing tumor progression. In this article, we summarize the regulating networks of TAM polarization and the mechanisms underlying TAM-facilitated metastasis. Based on the overview of current experimental evidence dissecting the critical roles of TAMs in tumor metastasis, we discuss and prospect the potential applications of TAM-focused therapeutic strategies in clinical cancer treatment at present and in the future.

Metastasis is the leading cause of high mortality in colorectal cancer (CRC), which is not only driven by changes occurring within the tumor cells, but is also influenced by the dynamic interaction between cancer cells and components in the tumor microenvironment (TME). Currently, the exploration of TME remodeling and its impact on CRC metastasis has attracted increasing attention owing to its potential to uncover novel therapeutic avenues. Noteworthy, emerging studies suggested that tumor-associated macrophages (TAMs) within the TME played important roles in CRC metastasis by secreting a variety of cytokines, chemokines, growth factors and proteases. Moreover, TAMs are often associated with poor prognosis and drug resistance, making them promising targets for CRC therapy. Given the prognostic and clinical value of TAMs, this review provides an updated overview on the origin, polarization and function of TAMs, and discusses the mechanisms by which TAMs promote the metastatic cascade of CRC. Potential TAM-targeting techniques for personalized theranostics of metastatic CRC are emphasized. Finally, future perspectives and challenges for translational applications of TAMs in CRC development and metastasis are proposed to help develop novel TAM-based strategies for CRC precision medicine and holistic healthcare.

Hand osteoarthritis is a leading cause of pain, disability, and reduced quality of life in older adults. Joint protection programs are recommended as a core component of self-management, but traditional delivery is limited by barriers to access. Digital programs can overcome these challenges for some people, but their reach and effectiveness depend on usability. We conducted a mixed methods usability study of a remotely delivered joint protection program designed for people with hand osteoarthritis. Twenty-three participants took part, recruited through purposeful sampling to ensure inclusion of groups often underrepresented in research. Usability was assessed using predefined task completion, browser-based eye-tracking, participant ratings, and think-aloud protocols, with iterative refinements applied between participants. Routine navigation tasks, such as navigating between different modules, accessing interactive activities, and viewing short videos, were consistently completed with high success. More complex interactive tasks, including drag-and-drop activities, scenario-based modules, and toggling videos to full screen, initially posed challenges. Over successive iterations, however, usability improved markedly, with later participants achieving near-perfect performance. Qualitative analysis revealed that participants valued clear language, short and focused videos, interactive elements, and the ability to proceed at their own pace, while raising concerns about excessive clicking, unclear instructions, and variation in age representation. Iterative refinements, including platform adjustments, clearer instructions and an introductory video, addressed these issues and contributed to improved performance. This study demonstrates that a remotely delivered, technology-enabled joint protection program for hand osteoarthritis is usable, accessible, and engaging across a diverse sample. Beyond refining the program itself, the study introduces a practical framework for iterative, equity-informed usability testing that can inform the design of future digital health interventions.

To mitigate problems such as ​​injection water channeling, abrupt water breakthrough, rapid decline in oil production accompanied by an abrupt rise in water cut, and poor mobilization of matrix oil that commonly arise in low-permeability fractured reservoirs after conventional water flooding, many Chinese oilfields have implemented chemical profile modification. However, the produced water used to prepare these chemicals contains high concentrations of divalent metal cations especially Fe 2+ which dramatically reduce the gel viscosity and thus degrade the conformance control performance. To address this issue, we developed a deep profile conformance control system tailored to the produced water from the Xingshugang block. We optimized both the type and concentration of each component in the formulation: a polymer concentration of 1000 mg/L TS1600; a chromium-based crosslinker at 130 mg/L; thiourea as an oxygen scavenger at 1000 mg/L; 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) as a metal ion chelating agent at 60 mg/L; and formaldehyde as a biocide at 100 mg/L. Laboratory tests demonstrated that, when prepared with produced water, the system forms a gel with a viscosity of 3704 mPa·s, achieves a plugging rate of 86.0%, and contributes to an enhanced oil recovery (EOR) of 17.82%. These results indicate that the proposed deep profile conformance control system exhibits excellent salt tolerance and enhanced profile modification performance in the presence of divalent metal ions.

Background Long non-coding RNAs (lncRNAs) are essential regulators of tumorigenesis and the development of colorectal cancer (CRC). Here, we aimed to investigate the role of lncRNA GAS6-AS1 in CRC and its potential mechanisms. Methods Bioinformatics analyses evaluated the level of GAS6-AS1 in colon cancer, its correlation with clinicopathological factors, survival curve and diagnostic value. qRT-PCR were performed to detect the GAS6-AS1 level in CRC samples and cell lines. The CCK8, EdU, scratch healing, transwell assays and animal experiments were conducted to investigate the function of GAS6-AS1 in CRC. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene analyses were carried out to reveal interaction between GAS6-AS1, TRIM14, FUS, and miR-370-3p/miR-1296-5p. Results GAS6-AS1 was greatly elevated in CRC and positively associated with unfavorable prognosis of CRC patients. Functionally, GAS6-AS1 positively regulates CRC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and induces CRC growth and metastasis in vivo. Moreover, GAS6-AS1 exerted oncogenic function by competitively binding to miR-370-3p and miR-1296-5p, thereby upregulating TRIM14. Furthermore, we verified that GAS6-AS1 and TRIM14 both interact with FUS and that GAS6-AS1 stabilized TRIM14 mRNA by recruiting FUS. Besides, rescue experiments furtherly demonstrated that GAS6-AS1 facilitate progression of CRC by regulating TRIM14. Conclusion Collectively, these findings demonstrate that GAS6-AS1 promotes TRIM14-mediated cell proliferation, migration, invasion, and EMT of CRC via ceRNA network and FUS-dependent manner, suggesting that GAS6-AS1 could be utilized as a novel biomarker and therapeutic target for CRC.

Benign prostatic hyperplasia (BPH) is a common urological condition affecting elderly men worldwide. In 2021, there were 112,502 (95% UI: 88,131.8–142,634.2) thousand prevalent cases globally, compared to 50,705.8 (95% UI: 38,735.5–65,693.4) thousand cases in 1990, representing a 122% increase. Over the past 30 years, the burden of BPH in low and low-middle socio-demographic index (SDI) regions have shown an upward trend and is projected to continue increasing over the next 15 years. Middle-SDI regions are facing the heaviest absolute burden of BPH. Despite declining prevalence, incidence, and disability-adjusted life years rates in high-middle SDI regions, the absolute BPH burden remains high, ranking second among the five SDI regions. In contrast, high-SDI regions exhibit a relatively low and stable BPH burden, though significant variations exist even among countries within the high-SDI category. Additionally, the global 65–69 age group bears the highest burden, with the 40–44 and 80+ age groups showing increasing trends. The burden of BPH varies significantly across regions, socioeconomic statuses, and countries, yet the absolute burden is generally increasing. The substantial regional differences in BPH burden underscore its widespread impact and potential controllability, indicating the need for more targeted healthcare efforts to address the growing BPH burden.

Estimated pulse wave velocity (ePWV) is a reliable method for evaluating arterial stiffness. While the prognostic significance of ePWV has been examined in a range of cardiovascular diseases, its particular importance in atrial fibrillation (AF) has not been thoroughly investigated. This study seeks to explore the relationship between ePWV and all-cause mortality (ACM) in individuals with AF. Patient information was collected from the Medical Information Mart for Intensive Care (MIMIC)-IV database, resulting in the selection of 14,704 individuals with AF for this study. The dominant end measure in this research was ACM at 30 days and 1 year, while the secondary end measure was ACM at 60 and 90 days post-admission to the ICU. Patients were divided into quartiles based on ePWV levels for analysis, and Kaplan-Meier curves were used to compare outcomes across groups. To explore the association between ePWV and patient prognosis, Cox proportional hazards models and restricted cubic splines (RCS) were employed. Additionally, subgroup and sensitivity analyses were conducted to verify the robustness of the results. The study included 14,704 participants, 8,816 (59.96%) of whom identified as male. Survival analysis demonstrated that elevated ePWV levels were associated with an increased risk of 30-day, 60-day, and 90-day ACM, as well as 1-year ACM. Cox proportional hazards regression analysis showed that, compared with the quartile Q1, the quartile Q2 (HR, 1.20; 95% CI: 1.06–1.37), Q3 (HR, 1.59; 95% CI: 1.40–1.81), and Q4 (HR, 2.38; 95% CI: 2.09–2.71) groups had a significantly increased risk of 30-day ACM. Similar results were observed for 1-year ACM and secondary outcomes. Additionally, RCS analysis revealed a J-shaped relationship between ePWV and ACM, with an inflection point of 9.8 m/s for both 30-day and 1-year ACM. When ePWV was ≥ 9.8 m/s, each 1-unit increase in ePWV was associated with a 16% increase in the risk of 30-day ACM (HR = 1.16, 95% CI = 1.14–1.19, p  < 0.001) and a 16% increase in the risk of 1-year ACM (HR = 1.16, 95% CI = 1.14–1.18, p  < 0.001). However, this association was not observed when ePWV levels were below 9.8 m/s. Sensitivity analyses confirmed the robustness of the results. The ePWV and SOFA composite score models both outperform their respective standalone models in predicting mortality. Elevated ePWV is linked to increased short- and long-term ACM in critically ill AF patients. ePWV may act as an important indicator for evaluating the severity of AF patients in the ICU and guiding therapeutic decisions.

The epithelium represents the first line of defense against viral infection, yet the precise mechanisms by which viruses penetrate this complex barrier remain incompletely understood. Single-virus tracking (SVT) has emerged as a powerful fluorescence microscopy approach to directly visualize viral dynamics with nanometer spatial precision and millisecond temporal resolution. In this review, we survey recent progress in SVT methodologies, from image-based approaches to active feedback techniques, and assess their capacity to resolve viral behavior in physiologically relevant epithelial models. We further evaluate advances in virus labeling strategies—including fluorescent proteins, organic dyes, and nanoparticles—that enable prolonged observation while preserving infectivity. By integrating developments in optical instrumentation and molecular labeling, SVT is increasingly capable of capturing critical processes, including extracellular diffusion, receptor engagement, internalization, and trans-epithelial transport. Finally, we discuss current challenges, including limited penetration depth, photobleaching, and the complexity of 3D epithelial tissues, and outline future opportunities to extend SVT towards in situ and tissue-level studies. Together, these advances position SVT as a transformative tool to illuminate virus–epithelium interactions and guide therapeutic strategies.

Background Multiscale sample entropy (MSE) is a prevalent complexity metric to characterize a time series and has been extensively applied to the physiological signal analysis. However, for a short-term time series, the likelihood of identifying comparable subsequences decreases, leading to higher variability in the Sample Entropy (SampEn) calculation. Additionally, as the scale factor increases in the MSE calculation, the coarse-graining process further shortens the time series. Consequently, each newly generated time series at a larger scale consists of fewer data points, potentially resulting in unreliable or undefined entropy values, particularly at higher scales. To overcome the shortcoming, a modified multiscale Renyi distribution entropy (MMRDis) was proposed in our present work. Methods The MMRDis method uses a moving-averaging procedure to acquire a family of time series, each of which quantify the dynamic behaviors of the short-term time series over the multiple temporal scales. Then, MMRDis is constructed for the original and the coarse-grained time series. Results The MMRDis method demonstrated superior computational stability on simulated Gaussian white and 1/f noise time series, effectively avoiding undefined measurements in short-term time series. Analysis of short-term heart rate variability (HRV) signals from healthy elderly individuals, healthy young people, and subjects with congestive heart failure and atrial fibrillation revealed that MMRDis complexity measurement values decreased with aging and disease. Additionally, MMRDis exhibited better distinction capability for short-term HRV physiological/pathological signals compared to several recently proposed complexity metrics. Conclusions MMRDis was a promising measurement for screening cardiovascular condition within a short time.

We present the first spatially resolved map of methanimine (CH2NH) in the prestellar core L1544 using the IRAM 30 m telescope. The 20,2–10,1 line at 127 GHz was mapped with 20″ resolution (∼2800 au), revealing extended CH2NH emission across the core. The peak line intensity coincides with the well-known c-C3H2 peak, while the integrated intensity peaks between the HNCO and dust continuum peaks due to broader linewidths in the latter region. Column densities of CH2NH are ∼(0.5–1.4×)1012 cm−2, corresponding to fractional abundances of 5 × 10−11–1 × 10−10, with a trend decreasing from the southern, carbon-chain rich region to the dust and HNCO peak in the north. Comparison with complementary molecular maps and the gas-grain chemical model of Sipilä et al. suggests that neutral–neutral gas-phase reactions and dissociative recombination dominate in the outer carbon-chain shell. This study demonstrates that CH2NH, a simple nitrogen- and carbon-bearing molecule previously detected with pointed observations in other cold cores, is present and spatially extended in the evolved prestellar core L1544. This indicates that prebiotic nitrogen-carbon chemistry continues efficiently up to the onset of gravitational collapse, providing key constraints for astrochemical models and the early stages of chemical complexity leading to amino acids.