Search Results (8,907)

Colorectal cancer (CRC) treatment with standard chemotherapeutics such as capecitabine (CAP) and irinotecan (IRT) is frequently limited by toxicity and resistance. To identify novel adjuvant strategies, we investigated the dichloromethane–methanol (DM) Soxhlet extract of the red alga Jania rubens, previously shown to exert intrinsic antiproliferative effects via reactive oxygen species (ROS) induction, inhibition of epithelial–mesenchymal transition (EMT), and suppression of TET enzymes. The present study evaluated the effect of the DM extract in combination with chemotherapeutic agents in HCT-116, Caco-2, and HT-29 colorectal cancer cell lines, assessing its potential to enhance treatment response. Co-treatment with the DM extract significantly enhanced the cytotoxic and anti-migratory effects of CAP and IRT in HCT-116 and Caco-2 cells. Combination treatment also impaired long-term clonogenic survival, suggesting the inhibition of therapy-resistant subpopulations. Flow cytometric analysis (Annexin V-FITC/PI) revealed a dose-dependent increase in apoptosis in HCT-116 cells following DM treatment. Western blot analysis further supported the pro-apoptotic activity of the DM extract by demonstrating reduced BCL-2 protein expression. The extract additionally modulated the mRNA expression levels of cytokines (TNF-α, IL-6, and IL-10), suggesting potential immunomodulatory effects in colorectal cancer cells. Notably, co-administration of IRT and the DM extract enhanced apoptosis, primarily through the downregulation of the anti-apoptotic gene BCL-2. Together, these findings indicate that the Jania rubens DM extract modulates multiple cellular pathways and enhances the response to conventional CRC chemotherapeutic agents. Full article

Expressway travel demand climbs steeply during public holidays, and the severe congestion that follows has become a principal constraint on both network operating efficiency and the quality of travel services. Dependable forecasting of holiday congestion, coupled with the practical realization of proactive management, accordingly carries considerable theoretical and practical weight for improving how expressways are operated and administered and for safeguarding efficient and safe public travel. Organized around the central theme of congestion prediction and proactive management for expressways over holiday periods, this paper reviews the progress of research across five interrelated areas: traffic speed and flow prediction methods; congestion state identification and forecasting; holiday travel characteristic analysis together with demand prediction; multi-source data fusion and congestion propagation mechanisms; and expressway traffic control together with traveler behavior guidance. Having surveyed the theoretical underpinnings, core technologies, and representative methods of each area, the paper concentrates in particular on the shortcomings and difficulties that existing studies encounter in coping with the hallmark features of holiday traffic, namely demand surges of short duration combined with pronounced spatiotemporal heterogeneity, and proceeds to outline promising avenues for subsequent research. Overall, the review seeks to provide wide-ranging literature support and a theoretical reference for developing technologies that predict and proactively manage congestion on expressways during public holidays. Full article

Background/Objectives: This study aims to analyze safety and effectiveness of imipenem/cilastatin sodium (IPM/CS) as an off-label embolic agent in acute lower gastrointestinal bleeding (LGIB). Methods: This is a multicentric prospective study including patients treated in emergency with endovascular embolization for acute LGIB. IPM/CS particles were prepared using one vial containing 500 mg/500 mg of IPM/CS in powder diluted with 5 mL of pure iodine contrast agent. Inclusion criteria were: acute bleeding managed with IMP/CS embolization, unfeasible/ineffective endoscopic management, availability of a pre-procedural contrast-enhanced Computed Tomography (CT) scan, pre- and post-procedural blood count, pre- and post-procedural hemodynamic balance evaluation, and follow-up to 30 days. Exclusion criteria were: patients treated in elective conditions, LGIB embolization performed without IMP/CS, IMP/CS adoption after other embolics, incomplete clinical–laboratoristic follow-up, and age < 18 years. Technical success was intended as angiographic disappearance of extravasation or significant reduction/stasis of blood flow to the target; clinical success was considered as hemoglobin values increase and/or stop transfusions and/or hemodynamic restoration. Result: Twenty-one patients were enrolled; bleeding etiologies included angiodysplasia, diverticular disease, gastrointestinal tumor-related bleeding, and post-surgical hemorrhage. Technical success rate was 100%, and clinical success rate at 30 days was 85.7%. Rebleeding occurred in three patients: two managed with surgery and one with coil re-embolization. Neither major and IPM/CS related complications occurred. Conclusions: In this study IPM/CS was a safe and feasible embolic agent in selected patients with acute LGIB; no bowel ischemia occurred during the 30 day follow-up. Future studies with larger samples are required to confirm these findings to include IPM/CS as an off-label alternative embolic agent in LGIB. Full article

Pulsatile blood flow is a fundamental characteristic of cardiovascular physiology that regulates endothelial function, vascular homeostasis, microcirculatory integrity, and organ adaptation through complex mechanobiological pathways. The widespread use of continuous-flow left ventricular assist devices (CF-LVADs) has created a unique clinical model of chronic pulsatility deprivation, whereas heart transplantation restores physiological pulsatile hemodynamics. This review examines the molecular, cellular, and systemic consequences of these contrasting circulatory states. Evidence from experimental and clinical studies indicates that reduced pulsatility during CF-LVAD support is associated with impaired endothelial mechanotransduction, glycocalyx disruption, oxidative stress, inflammatory activation, angiogenic dysregulation, acquired von Willebrand syndrome, and microvascular remodeling. These alterations contribute to bleeding, thrombosis, neurological events, and progressive end-organ dysfunction. In contrast, restoration of pulsatile flow following heart transplantation promotes recovery of endothelial signaling, nitric oxide bioavailability, vascular responsiveness, and tissue perfusion, although persistent immune-mediated injury may limit complete vascular normalization. Emerging concepts involving Piezo1 signaling, YAP/TAZ mechanotransduction, extracellular vesicles, immunometabolism, and multi-omics profiling further support the role of pulsatility as a biological regulator rather than a simple hemodynamic consequence of cardiac contraction. Understanding pulsatility-dependent cardiovascular remodeling may facilitate the development of next-generation circulatory support technologies and novel therapeutic strategies to preserve vascular health. Full article

Accurate runoff prediction is an essential foundation for water resource management, flood prevention, and drought warning. Despite the superior performance of deep learning models in runoff prediction, the high-dimensional hyperparameter optimization limits their widespread application. To address this challenge, this study proposed a hyperparameter optimization strategy that integrated Uniform Design (UD) and Meta-Learning (ML) within the Transformer framework (UD-ML-Transformer) for daily runoff prediction. Performance of the proposed model was systematically evaluated against five benchmark models, including the UD-Transformer, Particle Swarm Optimization (PSO)-Transformer, and three Receptance Weighted Key Value (RWKV)-based models (PSO-RWKV, UD-RWKV, and UD-ML-RWKV), using hydroclimatic data spanning 1980 to 2014 from the Rio Pueblo de Taos watershed in USA. Results showed that the UD-ML-Transformer model performed the best in both prediction accuracy and peak flow, with the highest Nash-Sutcliffe Efficiency (NSE) of 0.906, and the lowest Mean Squared Error (MSE), Root Mean Squared Error (RMSE), and Mean Absolute Error (MAE) of 0.004, 0.062, and 0.034, respectively. The UD-Transformer ranked second in performance, followed by the PSO-Transformer. The integrated UD-ML hyperparameter optimization strategy also improved the performance of RWKV-based models. Compared with the PSO-RWKV and UD-RWKV models, the UD-ML-RWKV model exhibited an NSE improvement of 0.45–7.65% and an RMSE reduction of 1.47–21.18%, respectively. Moreover, cross-watershed validation conducted in the Ford River watershed, USA, also demonstrated the satisfactory performance of the proposed UD-ML-Transformer model, with the highest NSE of 0.890, and the lowest MSE, RMSE, and MAE of 0.088, 0.296, and 0.141, respectively. These findings highlight the superiority of integrating UD and ML for hyperparameter optimization in runoff forecasting. Full article

The demand for a versatile and portable point-of-use (POU) sensor platform has surged due to the pandemic, especially in countries with limited medical laboratory facilities. We recently unveiled a portable, non-planar, interdigitated, flow-through, porous electrode platform that automatically measures electrochemical impedance spectroscopy (EIS) signals from various biomarkers. However, the packed powder exhibited a loss of performance over time due to displacement, leaching, and poor stability. Herein, we modified the packing strategy by synthesizing the sensing material within the channel, thereby improving adhesion, structural integrity, and stability. Leveraging the exceptional thermal stability, mechanical strength, and chemical resistance of polyimide (PI), we developed a novel fabrication approach that combines liquid-phase inversion and breath-figure techniques to create a porous PI manifold with single-walled carbon nanotubes (SWCNTs) under varying humidity conditions. Scanning electron microscope (SEM) analysis revealed that lower relative humidity (RH) conditions yield larger but less uniformly distributed pores, leading to increased channel pressure. The manifold demonstrated exceptional stability under rigorous flow conditions, withstanding a high flow rate of 30 µL/min while maintaining consistent pressure-EIS responses. The device produced a measurable proof-of-concept impedance response following exposure to a femtomolar concentration of complementary target ssDNA in 1× PBS within 15 min. A formal limit of detection was not determined in the present study. We developed a mechanically stable sensor design with improved durability under repeated flow conditions by systematically optimizing synthesis conditions and manifold configuration. This innovative fabrication strategy demonstrates the importance of packing methodology in sensor design and paves the way for robust, scalable, and efficient diagnostic solutions in resource-limited settings. Full article

Background: Glioblastoma (GBM) is the most aggressive primary brain tumour in adults and is characterised by poor prognosis and frequent resistance to temozolomide (TMZ)-based chemotherapy. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to GBM progression, therapeutic adaptation, and chemoresistance. This study investigated the relationship between TMZ responsiveness and the expression of selected lncRNAs in GBM cell lines exhibiting distinct sensitivity profiles. Methods: Human GBM cell lines (A172, U87, and T98G) and normal human astrocytes (NHA) were exposed to TMZ for 24–72 h. Cell viability, cell cycle distribution, MGMT protein expression, and expression levels of nine selected lncRNAs were analysed using MTT assay, flow cytometry, Western blot, and quantitative RT-PCR, respectively. Results: TMZ induced dose- and time-dependent reductions in cell viability in all analysed cell lines. A172 cells exhibited the greatest TMZ sensitivity, whereas T98G cells displayed the highest resistance. TMZ-sensitive GBM cells demonstrated pronounced G2/M cell cycle arrest, while T98G cells showed minimal cell cycle perturbation. MGMT protein expression was markedly elevated in T98G cells and decreased following exposure to higher TMZ concentrations. Distinct lncRNA expression profiles were identified among GBM cell lines. MALAT1 expression was consistently reduced, whereas NCK1-AS1 was strongly upregulated, particularly in T98G cells. TMZ exposure induced significant alterations in H19, PVT1, OIP5-AS1, and NCK1-AS1 expression, suggesting their potential involvement in adaptive resistance mechanisms. Conclusions: Collectively, these findings indicate that selected lncRNAs, particularly H19, MALAT1, NCK1-AS1, and PVT1, may contribute to TMZ resistance in GBM and could be promising biomarkers and therapeutic targets for precision oncology approaches. Full article

Background: Aorto–atrial fistula is a rare pathological communication associated with diagnostic difficulties, progressive hemodynamic consequences, and potential infective complications. Methods and Results: We present a 53-year-old woman with a long-standing congenital non-coronary sinus of Valsalva–to–right atrial fistula that had been followed for nine years under the working diagnosis of a Gerbode defect. The communication was first detected at the age of 44 years during pregnancy and was managed conservatively while the patient remained largely asymptomatic. At the age of 53 years, recurrent exertional dyspnea prompted definitive reassessment. Right heart catheterization demonstrated a hemodynamically significant left-to-right shunt at the right atrial level, with a pulmonary-to-systemic blood flow (Qp/Qs) ratio of 2.1. Intraoperatively, the communication was shown to originate immediately above the non-coronary cusp and drain into the right atrium, establishing the diagnosis of a congenital aorto–right atrial fistula. A granulomatous, windsock-like endocardial lesion was identified at its right atrial opening, and Staphylococcus capitis was isolated from surgically obtained tissue. Histopathology showed nonspecific regressive changes without specific features of active infective endocarditis. The fistula was closed with an autologous pericardial patch, and intravenous flucloxacillin was administered because of probable localized infective involvement. Conclusions: This case illustrates the diagnostic difficulty of distinguishing an aorto–atrial fistula from a Gerbode defect and supports careful multimodality evaluation of the anatomical origin and flow characteristics of intracardiac shunts. Persistent high-velocity flow may contribute to endocardial injury and create a substrate for subsequent bacterial colonization, although causality cannot be established from a single case. Isolation of a low-virulence skin commensal from pathological cardiac tissue should be interpreted in the complete clinical, operative, microbiological, and histopathological context rather than automatically classified as contamination. Full article

In vertebrates, circulating and tissue-resident immune cells contribute to host defense and tissue homeostasis. Their balance is maintained through hematopoiesis and anatomical reservoirs. In mollusks, this balancing is poorly investigated. Thus, the dynamics of circulating and tissue-resident hemocytes after a hemolymph withdrawal were analyzed in Pomacea canaliculata, a snail that allows repeated hemolymph withdrawals and possesses posterior kidney (PK) cell aggregates known as hemocyte islets. In the absence of specific hemocyte markers, flow cytometry data revealed dynamic changes in circulating hemocyte number and populations within 48 h following hemolymph withdrawal. In addition, computer-assisted image analysis of histological sections showed a significant transient reduction in PK hemocyte-islet area. Analyses of publicly available P. canaliculata transcriptomes revealed predominant and highly variable expression of two hematopoiesis-related genes, namely Transglutaminase (PcTGase) and Hematopoietically expressed homeobox protein (PcHhex), in circulating hemocytes and PK. Fluorescence in situ hybridization highlighted constitutive PcTGase and PcHhex expression within PK hemocyte islets. RT-qPCR experiments confirmed transcriptomic data on PcTGase and PcHhex constitutive expression, without significant modulation following hemolymph withdrawal. Collectively, these findings provide the first evidence of parallel recovery dynamics involving circulating hemocytes and PK hemocyte islets in P. canaliculata. Full article

Background: Drug resistance and treatment-associated toxicity remain major limitations of conventional chemotherapy for triple-negative breast cancer (TNBC). Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, has demonstrated anticancer properties and may enhance the therapeutic efficacy of docetaxel (DTX) through complementary molecular mechanisms. Objective: To investigate whether TQ potentiates the antitumor activity of DTX in MDA-MB-231 TNBC cells by affecting apoptosis, oxidative stress, wound closure, and PI3K/AKT pathway-related gene expression. Methods: MDA-MB-231 TNBC cells and HaCaT keratinocytes were treated with TQ, DTX, or their combination. Cell viability was determined using the MTT assay, and drug interactions were evaluated by the Chou–Talalay combination index (CI) method. Apoptosis, intracellular reactive oxygen species (ROS) production, ROS rescue experiments using N-acetyl-L-cysteine (NAC), caspase-9 expression, wound closure, and gene-expression changes were assessed using Annexin V/PI flow cytometry, DCFH-DA-based flow cytometric and fluorescence analyses, immunocytochemistry, wound-healing assay, and quantitative real-time PCR (qRT-PCR), respectively. Bioinformatic analyses were performed to identify signaling pathways associated with the observed molecular alterations. Results: The TQ + DTX combination demonstrated synergistic cytotoxicity and significantly increased apoptotic cell death compared with either monotherapy. Combination treatment markedly enhanced intracellular ROS accumulation, whereas NAC pretreatment significantly attenuated ROS generation and partially reversed the cytotoxic and pro-apoptotic effects, suggesting the involvement of ROS in the observed antitumor effects. Caspase-9 immunoreactivity was markedly increased following combination treatment, suggesting the involvement of the intrinsic apoptotic pathway. Furthermore, the combination significantly suppressed wound closure and downregulated BCL2, PIK3CA, and AKT1 while upregulating BAX, CASP9, and PTEN. Bioinformatic analyses identified apoptosis, p53, PI3K/AKT, mTOR, and MAPK signaling as the principal pathways potentially associated with the observed gene expression changes. Conclusions: TQ potentiates the antitumor activity of DTX, with the involvement of oxidative stress, apoptotic signaling, suppression of wound closure, and regulation of PI3K/AKT pathway-related gene expression in TNBC cells. These findings provide evidence supporting further preclinical investigation of the TQ + DTX combination as a promising therapeutic strategy for triple-negative breast cancer. Full article

High renewable penetration, distributed energy resources, and fast-varying electric loads are shifting smart-grid planning from energy-balance simulation toward quality-aware operational assessment. Full-unit benchmark models (FULL) preserve unit commitment, ramping memory, and reserve feasibility but are expensive for repeated annual studies, whereas conventional equivalent aggregation (EQ) can overstate the realizable flexibility of heterogeneous units. This paper proposes quality-aware flexibility-envelope aggregation (QFEA), which separates units by inherited boundary state, ranks them by renewable-following flexibility, constructs conservative cluster envelopes, and couples reduced optimization with feasible disaggregation and state write-back. The model coordinates renewable curtailment, reserve sufficiency, tie-line ramping, and a normalized quality-stress proxy without claiming to replace detailed power-flow, harmonic, or electromagnetic studies. In the nominal single-region case, QFEA reduces the number of commitment objects by 46.2% and computation time by 63.7%, while limiting total-cost deviation to 1.1% and renewable-curtailment deviation to 0.2 percentage points. In 20 matched 24-h stress scenarios, its mean quality-stress index is 2.56%, compared with 2.58% for FULL and 6.57% for EQ. A separate 13–104-unit simplified scaling test keeps inverse-mapping closure error below 5.2 × 10⁻⁹ MWh and disaggregation below 1.3% of measured end-to-end time. The results identify QFEA as a traceable intermediate model for renewable-integration screening when annual computational efficiency and implementable unit trajectories are both required. Full article

Background: Multiple myeloma (MM) is an incurable hematologic malignancy, and the majority of patients eventually relapse due to persistent myeloma cells. While minimal residual disease (MRD) reflects tumor burden, the host immune system also plays a crucial role in disease control. Our study aimed to evaluate MRD, complete blood count (CBC), and immune cell profiles in MM patients treated with bortezomib/adriamycin/dexamethasone (PAD) chemotherapy followed by autologous stem cell transplantation (ASCT) to determine their prognostic value and interplay. Objectives: This study aims to identify markers indicative of a favorable prognosis in MM patients. Methods: CBC data were collected from 93 MM patients at diagnosis, prior to ASCT, and 3 months post-ASCT. Immune cell profiles were assessed via flow cytometry using fresh peripheral blood samples from a subset of 33 prior to ASCT and 3 months post-ASCT. We subsequently investigated the associations between MRD status and prognosis, the predictive value of CBC, and the longitudinal changes in immune cell profiles and their correlation with clinical outcomes. Results: An increased frequency of negative immunomodulatory cell subsets and activated T lymphocytes prior to ASCT were associated with a poor prognosis. Conversely, lower levels of exhausted T lymphocytes, alongside higher levels of functional T cells and marginal zone B cells post-ASCT, predicted a favorable prognosis. Conclusions: Our study demonstrates that pre-ASCT immune status, post-ASCT immune reconstitution, and MRD status at 3 months post-ASCT are closely associated with clinical outcomes in MM patients. These findings underscore the critical importance of regular immune monitoring in the comprehensive management of MM. Full article

Long-term phases (lasting 10–15 years or more) of decreased and increased annual and seasonal runoff and related differences in the frequencies of low-water and high-water river flow years were identified for the Lena across Kyusyur and Tabaga and its tributary, the Aldan in Verkhoyanski Perevoz, for observation periods beginning in the 1930–1940s. Phase boundaries were identified by cumulative deviation curves and the statistical homogeneity of runoff time series. The frequencies of abnormal years were estimated based on the empirical exceedance probability curves, derived from multi-year time series of annual and seasonal flows. Two main long-lasting, quasi-synchronous contrasting phases were revealed on each of the rivers under consideration during an 80-year series of observations for both annual and seasonal runoff. At first, there was a phase of decreased runoff, which was followed by a phase of increased runoff during the period of modern global warming. These contrasting phases exhibit quasi-synchronicity not only within the same river but also across different rivers. However, the duration and magnitude of the flow difference between phases vary both on each river and between them. The phases of increased runoff are characterized by a noticeably higher frequency of high-water years (when runoff is at least 25% of the exceedance probability) and a lower frequency of low-water years (when runoff is at least 75% of the exceedance probability). This inverse relationship has been revealed for the phases of decreased runoff. Full article

Chloride-induced corrosion is a major threat to excavated bronze artifacts, yet conventional alkaline desalination requires repeated solution replacement and generates secondary chemical waste. Herein, a series of BiOCl-loaded carbon nanofiber composites (CNFs@BiOCl-X) were prepared by KOH activation followed by hydrothermal growth of BiOCl, aiming to develop regenerable electrodes for chloride removal in capacitive deionization systems. Alkali activation regulated the surface roughness, oxygen-containing functional groups, hydrophilicity, and BiOCl loading of CNFs, while the three-dimensional conductive network helped immobilize BiOCl nanostructures and buffer the volume variation associated with reversible Bi/BiOCl conversion. Electrochemical analyses confirmed the pseudocapacitive chloride-storage behavior of the composites, with ion removal governed by the coupled effects of BiOCl redox activity, charge transfer, and interfacial ion transport. In a fixed-electrode membrane capacitive deionization system, CNFs@BiOCl-2 exhibited the best overall performance, delivering a salt adsorption capacity of 100.44 mg g⁻¹ at 1.4 V and retaining 93.17% of its desalination capacity after 35 cycles at 1.2 V. For flow-electrode capacitive deionization, the higher BiOCl-loading CNFs@BiOCl-5 showed superior utilization of active sites and achieved 94.75% NaCl removal from a 1000 mg L⁻¹ solution within 3 h, with an average desalination rate of 15.48 μg cm⁻² min⁻¹ and an energy consumption of 0.88 kWh kg⁻¹-NaCl. These findings demonstrate that rationally matching BiOCl loading with electrode configuration enables efficient and sustainable chloride management, offering a promising electrochemical strategy for conservation electrolytes and related desalination applications. Full article

Stable drainage of coalbed methane wells is essential for reducing reservoir pressure and promoting methane desorption. However, coal fines carried by produced water tend to accumulate and deposit within the standing valves of drainage pumps. To address this common problem, this study investigates the transport characteristics of coal fines within the standing valve during the liquid-dominated water-pumping stage of the plunger upstroke, with the standing valve fully open. Theoretical calculations, numerical simulations, and settling experiments were conducted for three coal fines size fractions of 60–100, 100–200, and 200–400 mesh to validate the model’s predictive capability for coal fines motion. The results show that the RNG k–ε model has the lowest mean absolute relative error, at 14.50%. A solid–liquid two-phase flow model was employed to comparatively analyze five valve seat cone angles ranging from 105° to 165° and representative inlet velocities of 0.1–0.4 m/s. The results indicate that the mixture within the standing valve accelerates markedly while passing through the narrow clearance between the valve ball and the valve seat and then decelerates in the region above the valve ball. The region above the valve ball and the valve seat transition region are the primary locations of instantaneous coal fines enrichment. Increasing the inlet velocity generally enhances coal fines transport capacity and reduces the local maximum solid-phase volume fraction. Larger coal fines particles exhibit more pronounced inertial deviation and a higher degree of local enrichment, whereas smaller particles show stronger flow-following behavior and a more dispersed spatial distribution. The results further indicate that, within the investigated structural range, the 150° valve seat cone angle provides the best overall balance between coal fines transport capacity and hydraulic resistance. Ultimately, the findings provide a theoretical foundation and methodological reference for understanding the anti-clogging mechanisms of CBM pump standing valves, optimizing structural parameters, and guiding the blockage-resistant design of downhole flow components. Full article