Search Results (53,347)

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article

The transportation sector, as a major source of carbon emissions, plays a crucial role in the realization of dual carbon goals worldwide. In this study, an improved least absolute shrinkage and selection operator (LASSO) is used to identify six key factors affecting transportation carbon emissions (TCEs) in China. Aiming at the spatio-temporal characteristics of transportation carbon emissions, a CNN-BiLSTM neural network model is constructed for the first time for prediction, and an improved whale optimization algorithm (EWOA) is introduced for hyperparameter optimization, finding that the prediction model combining spatio-temporal characteristics has a more significant prediction accuracy, and scenario forecasting was carried out using the prediction model. Research indicates that over the past three decades, TCEs have demonstrated a rapid growth trend. Under the baseline, green, low-carbon, and high-carbon scenarios, peak carbon emissions are expected in 2035, 2031, 2030, and 2040. The adoption of a low-carbon scenario represents the most advantageous pathway for the sustainable progression of China’s transportation sector. Consequently, it is imperative for China to accelerate the formulation and implementation of low-carbon policies, promote the application of clean energy and facilitate the green transformation of the transportation sector. These efforts will contribute to the early realization of dual-carbon goals with a positive impact on global sustainable development. Full article

Background: Workplace mobbing is a widespread phenomenon with serious psychological and emotional consequences on employees’ emotional well-being. Psychological resilience has been identified as a potential protective factor against such adverse outcomes. Aim: This study investigates the relationship between workplace mobbing and emotional well-being, as expressed through positive and negative affect, and examines the mediating role of psychological resilience in this association. Methods: Ninety nurses participated in this cross-sectional study. Data were collected using the Connor–Davidson Resilience Scale (CD-RISC), the Workplace Psychologically Violent Behaviors (WPVB) scale, and the Positive and Negative Affect Schedule (PANAS). Statistical analyses included correlation, multiple regression, and mediation using bootstrapped confidence intervals. Results: Resilience was strongly associated with positive affect (r = 0.74, p < 0.001) and inversely with negative affect (r = −0.46, p < 0.001). Mobbing was significantly related to increased negative affect (β = 0.12, p < 0.001) but not to positive affect. Resilience emerged as the strongest predictor of emotional outcomes and partially mediated the relationship between “Attack on professional role” and negative affect. Conclusions: Psychological resilience plays a key protective role in moderating the emotional impact of workplace mobbing. Enhancing resilience in healthcare professionals may mitigate the negative emotional effects of mobbing, although it does not fully buffer against all its consequences. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article

The COVID-19 pandemic precipitated unprecedented social isolation measures, profoundly disrupting daily life, educational routines, and mental health worldwide. University students, already susceptible to psychological distress, encountered intensified challenges under remote learning and prolonged confinement. This longitudinal study examined fluctuations in anxiety and mood among 102 Brazilian university students during the pandemic, distinguishing between those solely engaged in academic pursuits and those simultaneously balancing work and study. Data collected via the Brunel Mood Scale and State-Trait Anxiety Inventory in April and July 2021 revealed that students exclusively focused on studies exhibited significant increases in depressive symptoms, anger, confusion, and anxiety, alongside diminished vigor. Conversely, participants who combined work and study reported reduced tension, fatigue, confusion, and overall mood disturbance, coupled with heightened vigor across the same period. Notably, women demonstrated greater vulnerability to anxiety and mood fluctuations, with socioeconomic disparities particularly pronounced among females managing dual roles, who reported lower family income. These findings suggest that occupational engagement may serve as a protective factor against psychological distress during crises, underscoring the urgent need for tailored mental health interventions and institutional support to mitigate the enduring impacts of pandemic-related adversities on the student population. Full article

Background: Biological aging influences cancer outcomes, but its changes during chemotherapy and impact on chemotoxicity in colorectal cancer (CRC) remain underinvestigated. We examined (1) trajectories of biological aging (using Levine Phenotypic Age) during six months of chemotherapy, (2) sociodemographic and clinical risk factors for biological aging, and (3) links between biological aging and chemotoxicity. Methods: Using data from electronic health records (2013–2019) from 1129 adult CRC patients, we computed biological aging (raw Levine Phenotypic Age and its age acceleration [Levine Phenotypic Age–chronological age]) from routine blood tests (e.g., complete blood counts, hepatorenal/inflammatory markers). Chemotoxicity was identified primarily via International Classification of Diseases (ICD-9 and -10) codes. Results: Chemotherapy accelerated biological aging over time. Biological aging at baseline and changes over time predicted chemotoxicity. However, changes in biological aging over time showed stronger associations than baseline biological aging. Advanced cancer stages, higher comorbidity burden, and socioeconomic disadvantage (especially area-level deprivation) were associated with accelerated biological aging at baseline and over time. Biological aging occurred across both young and older adults. Conclusions: Levine Phenotypic Age, computed from routine blood tests in EHRs, offers a feasible clinical tool for aging-related chemotoxicity risk stratification. Validation in diverse cohorts and the development of predictive models are needed. Full article

Curli fimbriae are a major component of biofilm formation in Escherichia coli, and their expression is regulated by numerous transcription factors and small regulatory RNAs (sRNAs). The RcsD-RcsC-RcsB phosphorelay system, which is involved in the envelope stress response, plays a role in this regulation. In this study, we report that DNase-I footprinting analysis revealed that the response regulator RcsB interacts with the −31 to +53 region of the promoter region of csgD, which encodes a major regulator of biofilm formation, and thus contributes to its transcriptional repression. Additionally, overexpression of RcsB or RcsB D56A that could not be phosphorylated by the histidine kinases RcsC and D both significantly reduced csgD expression and suppressed Curli formation. This indicates that the phosphorylation of RcsB has an insignificant impact on its affinity for its operator sites. Furthermore, we confirm that RcsB binds cooperatively to the csgD promoter region in the presence of the nucleoid-associated protein H-NS. Our study also confirms that RcsB positively regulates the expression of an sRNA, RprA, which is known to reduce mRNA csgD mRNA translation RprA via its binding to the 5′-untranslated region (UTR) of csgD. These findings indicate that, in E. coli, the RcsBCD system suppresses csgD expression through both direct transcriptional repression by the regulator RcsB and translational repression by the sRNA RprA. Full article

As geographic information visualization continues to gain prominence, dynamic symbols are increasingly employed in map-based applications. However, the optimal visual coding for dynamic point symbols—particularly concerning encoding type, animation rate, and modulation area—remains underexplored. This study examines how these factors influence user performance in visual search tasks through two eye-tracking experiments. Experiment 1 investigated the effects of two visual coding factors: encoding types (flashing, pulsation, and lightness modulation) and animation rates (low, medium, and high). Experiment 2 focused on the interaction between encoding types and modulation areas (fill, contour, and entire symbol) under a fixed animation rate condition. The results revealed that search performance deteriorates as the animation rate of the fastest target symbol exceeds 10 fps. Flashing and lightness modulation outperformed pulsation, and modulation areas significantly impacted efficiency and accuracy, with notable interaction effects. Based on the experimental results, three visual coding strategies are recommended for optimal performance in map-based interfaces: contour pulsation, contour flashing, and entire symbol lightness modulation. These findings provide valuable insights for optimizing the design of dynamic point symbols, contributing to improved user engagement and task performance in cartographic and geovisual applications. Full article

The green renovation of existing residential buildings is a key way for the construction industry to achieve sustainable development and the dual carbon goals of China, which makes it urgent to make collaborative decisions among multiple stakeholders. However, because of divergent interests and risk perceptions among governments, energy service companies (ESCOs), and owners, the implementation of green renovation is hindered by numerous obstacles. In this study, we integrated prospect theory and evolutionary game theory by incorporating core prospect-theory parameters such as loss aversion and perceived value sensitivity, and developed a psychologically informed tripartite evolutionary game model. The objective was to provide a theoretical foundation and analytical framework for collaborative governance among stakeholders. Numerical simulations were conducted to validate the model’s effectiveness and explore how government regulation intensity, subsidy policies, market competition, and individual psychological factors influence the system’s evolutionary dynamics. The findings indicate that (1) government regulation and subsidy policies play central guiding roles in the early stages of green renovation, but the effectiveness has clear limitations; (2) ESCOs are most sensitive to policy incentives and market competition, and moderately increasing their risk costs can effectively deter opportunistic behavior associated with low-quality renovation; (3) owners’ willingness to participate is primarily influenced by expected returns and perceived renovation risks, while economic incentives alone have limited impact; and (4) the evolutionary outcomes are highly sensitive to parameters from prospect theory, The system’s evolutionary outcomes are highly sensitive to prospect theory parameters. High levels of loss aversion (λ) and loss sensitivity (β) tend to drive the system into a suboptimal equilibrium characterized by insufficient demand, while high gain sensitivity (α) serves as a key driving force for the system’s evolution toward the ideal equilibrium. This study offers theoretical support for optimizing green renovation policies for existing residential buildings in China and provides practical recommendations for improving market competition mechanisms, thereby promoting the healthy development of the green renovation market. Full article

South Dongting Lake is an essential aquatic ecosystem that receives substantial water inflows from the Xiangjiang and Zishui Rivers. However, it is significantly impacted by human activities, including mining, smelting, and farming. These activities have led to serious contamination of the lake’s sediments with heavy metals (HMs). This study investigated the distribution, mobility, and influencing factors of HMs at the sediment–water interface. To this end, sediment samples were analyzed from three key regions (Xiangjiang River estuary, Zishui River estuary, and northeastern South Dongting Lake) using traditional sampling methods and Diffusive Gradients in Thin Films (DGT) technology. Analysis of fifteen HMs (Pb, Bi, Ni, As, Se, Cd, Sb, Mn, Zn, V, Cr, Cu, Tl, Co, and Fe) revealed significant spatial heterogeneity. The results showed that Cr, Cu, Pb, Bi, Ni, As, Se, Cd, Sb, Mn, Zn, and Fe exhibited high variability (CV > 0.20), whereas V, Tl, and Co demonstrated stable concentrations (CV < 0.20). Concentrations were found to exceed background values of the upper continental crust of eastern China (UCC), Yangtze River sediments (YZ), and Dongting Lake sediments (DT), particularly at the Xiangjiang estuary (XE) and in the northeastern regions. Speciation analysis revealed that V, Cr, Cu, Ni, and As were predominantly found in the residual fraction (F4), while Pb and Co were concentrated in the oxidizable fraction (F3), Mn and Zn appeared primarily in the exchangeable fractions (F1 and F2), and Cd was notably dominant in the exchangeable fraction (F1), suggesting a high potential for mobility. Additionally, DGT results confirmed a significant potential for the release of Pb, Zn, and Cd. Contamination assessment using the Pollution Load Index (PLI) and Geoaccumulation Index (Igeo) identified Pb, Bi, Ni, As, Se, Cd, and Sb as major pollutants. Among these, Bi and Cd were found to pose the highest risks. Furthermore, the Risk Assessment Code (RAC) and the Potential Ecological Risk Index (PERI) highlighted Cd as the primary ecological risk contributor, especially in the XE. The study identified sediment grain size, pH, electrical conductivity, and nutrient levels as the primary influencing factors. The PMF modeling revealed HM sources as mixed smelting/natural inputs, agricultural activities, natural weathering, and mining/smelting operations, suggesting that remediation should prioritize Cd control in the XE with emphasis on external inputs. Full article

Although PD-1/PD-L1 inhibitors have transformed cancer immunotherapy, a substantial proportion of patients derive no clinical benefit due to resistance driven by the tumour microenvironment (TME). Transforming growth factor-β (TGF-β) is a key immunosuppressive cytokine implicated in this resistance. Several bifunctional antibodies that co-target PD-1 and TGF-β signalling have entered clinical trials and shown encouraging efficacy, but the mechanistic basis of their synergy is not fully understood. Here, we engineered 015s, a bifunctional fusion antibody that simultaneously targets murine PD-1 and TGF-β and evaluated its antitumour efficacy and mechanistic impact in pre-clinical models. Antibody 015s exhibited high affinity, dual target binding, and the effective inhibition of PD-1 and TGF-β signalling. In vivo, 015s significantly suppressed tumour growth compared with anti-mPD-1 or TGF-β receptor II (TGF-βRII) monotherapy. When combined with the CD24-targeted ADC, 015s produced even greater antitumour activity and achieved complete tumour regression. Mechanistic studies demonstrated that 015s significantly reduced tumour cell migration and invasion, reversed epithelial–mesenchymal transition (EMT), decreased microvascular density, and attenuated collagen deposition within the TME. Antibody 015s also decreased bioactive TGF-β1 and increased intratumoural IFN-γ, creating a more immunostimulatory milieu. These findings support further development of PD-1/TGF-β bifunctional antibodies for cancers with high TGF-β activity or limited response to immune checkpoint blockade. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

Early-career teachers (ECTs) entered the profession during the COVID-19 pandemic, a period that introduced unique stressors to an already-demanding career phase. This systematic review examines empirical studies published between 2020 and February 2025 to explore how the pandemic influenced ECT wellbeing, with particular attention to stressors and protective factors impacting long-term retention and professional sustainability. Guided by PRISMA protocols, databases including Web of Science, ERIC, Google Scholar, and Scopus were searched, screening 470 records and identifying 30 studies that met inclusion criteria: peer-reviewed, empirical, focused on early-career teachers (within the first five years), and situated in or explicitly addressing the pandemic and its ongoing impacts. The results of Braun and Clarke’s thematic analysis (2006) revealed that pandemic-related challenges such as increased workload, professional isolation, disrupted induction processes, and emotional strain have persisted into the post-pandemic era, contributing to sustained risks of burnout and attrition. Regardless, protective factors identified during the pandemic—including high-quality mentoring, structured induction programmes, collegial support, professional autonomy, and effective individual coping strategies—continue to offer essential support, enhancing resilience and professional wellbeing. These findings underscore the necessity of institutionalising targeted supports to address the enduring effects of pandemic-related stressors on ECT wellbeing. By prioritising sustained mental health initiatives and structural supports, education systems can effectively mitigate long-term impacts and improve retention outcomes for early-career teachers in a post-pandemic educational landscape. Full article