Search Results (11,136)

TIGIT and its ligand CD155 (PVR) are emerging immune checkpoints in colorectal cancer (CRC), but their associations with mutational subtypes and the tumor immune milieu remain unclear. We quantified TIGIT and CD155 proteins by ELISA in paired CRC tumors and matched surgical margins (n = 131) and evaluated associations with clinicopathological features, MSI status, and KRAS/NRAS/BRAF/PIK3CA/AKT1 mutations (n = 104). Both TIGIT and CD155 were significantly elevated in tumor tissue versus margins (p < 0.0001) and showed no association with TNM stage, clinical stage, grade, or tumor location. TIGIT levels were higher in MSI than MSS tumors and in BRAF-mutant compared to BRAF wild-type tumors, while CD155 expression showed no consistent MSI- or mutation-dependent differences. Cytokine profiling identified IFN-g as the only shared positive associate of TIGIT and CD155; CD155 additionally associated with TRAIL, IL-1Ra, M-CSF, and PDGF-bb. In external transcriptomic validation (TCGA-CRC), GSEA indicated enrichment of interferon/inflammatory programs in TIGIT-high tumors, while CD155-high tumors preferentially showed proliferation-related MYC/E2F/G2M signatures. Together, these findings support tumor-wide upregulation of the TIGIT/CD155 axis in CRC and suggest that TIGIT, more than CD155, tracks with MSI/BRAF-associated immune activation, providing a rationale for patient stratification in checkpoint-directed immunotherapy. Full article

We present an adaptive governance engine for blockchain-enabled Vehicular Ad Hoc Networks (VANETs) that regulates the latency–energy–coherence trade-off under rapid topology changes. The core contribution is an Ideal Information Cycle (an operational abstraction of information injection/validation) and a modular VANET Engine implemented as a real-time control loop in NS-3.35. At runtime, the Engine monitors normalized Shannon entropies—informational entropy S over active transactions and spatial entropy $H_{\mathrm{spatial}}$ over occupancy bins (both on $[0,1]$)—and adapts the consensus mode (latency-feasible PoW versus signature/quorum-based modes such as PoS/FBA) together with rigor parameters via calibrated policy maps. Governance is formulated as a constrained operational objective that trades per-block resource expenditure (radio + cryptography) against a Quality-of-Information (QoI) proxy derived from delay/error tiers, while maintaining timeliness and ledger-coherence pressure. Cryptographic cost is traced through counted operations, $E_{\mathrm{crypto}}=e_h{n}_{\mathrm{hash}}+e_{\mathrm{sig}}{n}_{\mathrm{sig}}$, and coherence is tracked using the LCP-normalized definition $D_{\mathrm{ledger}}\left(t\right)$ computed from the longest common prefix (LCP) length across nodes. We evaluate the framework under urban/highway mobility, scheduled partitions, and bounded adversarial stressors (Sybil identities and Byzantine proposers), using 600 s runs with 30 matched random seeds per configuration and 95% bias-corrected and accelerated (BCa) bootstrap confidence intervals. In high-disorder regimes ($S\gtrsim 0.8$), the Engine reduces total per-block energy (radio + cryptography) by more than 90% relative to a fixed-parameter PoW baseline tuned to the same agreement latency target. A consensus-first triggering policy further lowers agreement latency and improves throughput compared with broadcast-first baselines. In the emphasized urban setting under high mobility ($v=30$ m/s), the Engine keeps agreement/commit latency in the sub-100 ms range while maintaining finality typically within sub-150 ms ranges, bounds orphaning (≤10%), and reduces average ledger divergence below $0.07$ at high spatial disorder. The main evaluation is limited to $N\le 100$ vehicles under full PHY/MAC fidelity. PoW targets are intentionally latency-feasible and are not intended to provide cryptocurrency-grade majority-hash security; operational security assumptions and mode transition safeguards are discussed in the manuscript. Full article

Serum lactate dehydrogenase (LDH) is a recognized prognostic biomarker in human lymphomas, yet its clinical significance in canine lymphoma remains insufficiently characterized. This study aimed to quantify serum LDH levels in healthy dogs and dogs with high-grade multicentric lymphoma (ML) (predominantly B-cell) and to investigate correlations between LDH levels and established clinical and laboratory prognostic indicators. Twenty-seven dogs were prospectively enrolled: healthy controls (G1, n = 7) and dogs with high-grade ML (G2, n = 20). Immunophenotyping was performed by immunohistochemistry (CD3/CD79a). LDH concentrations were measured at diagnosis (T0) and after six weeks of CHOP-based induction chemotherapy (T1). Statistical analyses included Kruskal–Wallis, Wilcoxon signed-rank, Pearson’s correlation, and mixed-effects models. Dogs with high-grade ML exhibited significantly elevated LDH levels compared to controls (median 545.5 U/L, range: 288.2–2816 U/L vs. 143 U/L, range: 66–272; p < 0.001). Dogs with thrombocytopenia had higher baseline LDH (median 746 U/L, range: 612–921; p = 0.006) and greater reductions following chemotherapy (median −1011.7 U/L, range: −159 to −2064; p = 0.004). LDH levels declined significantly after treatment (overall median reduction 50.7%; post-chemotherapy range: 60.4–752 U/L; n = 15; p = 0.013), with normalization achieved in 77.8% of dogs with complete response versus 16.7% with partial or progressive disease (p = 0.02). We confirmed that serum LDH is significantly elevated in dogs with high-grade ML and declines following effective chemotherapy, supporting its utility as a dynamic biomarker of tumor burden and treatment response. Thrombocytopenic dogs may represent a biologically distinct subset warranting further investigation. Full article

The Lunar Gateway is a planned small space station that will orbit the Moon and serve as a central hub for NASA’s Artemis program to return humans to the lunar surface and to prepare for Mars missions. This work presents a hybrid optimization strategy for designing minimum-fuel transfers from an Earth orbit to a Lunar Near-Rectilinear Halo Orbit. The corresponding optimal control problem—crucial for missions to NASA’s Lunar Gateway—is characterized by a high-dimensional, non-convex solution space due to the multi-body gravitational environment. To tackle this challenge, a two-stage hybrid optimization scheme is employed. The first stage uses a Genetic Algorithm heuristic as a global search strategy, to identify promising feasible trajectory solutions. Subsequently, the initial solution guess (or guesses) produced by GA are improved by a local optimizer based on a Sequential Quadratic Programming method: from a suitable initial guess, SQP rapidly converges to a high-precision feasible solution. The proposed methodology is applied to a representative cargo mission case study, demonstrating its efficiency. Our numerical results confirm that the hybrid optimization strategy can reliably generate mission-grade quality trajectories that satisfy stringent constraints while minimizing propellant consumption. Our analysis validates the combined GA-SQP optimization approach as a robust and efficient tool for space mission design in the cislunar environment. Full article

Gastric cancer (GC) is the fifth most common cancer worldwide, with the highest incidence in East Asia. Although H. pylori is a well-known risk factor, carcinogenesis can occur independently of H. pylori infection, and approximately 43% of adults carry H. pylori as part of their native microbiota. This study aimed to identify potential oral and gastric microbial markers across different histological stages of GC in both H. pylori-positive and -negative patients. Buccal swabs and gastric mucosa samples were collected from patients with intestinal metaplasia, low-grade dysplasia, high-grade dysplasia, early GC, or advanced GC. Total DNA was extracted, and 16S rRNA gene amplicon sequencing was performed. Microbiome diversity generally remained stable across histological stages, with no directional shifts in community structure. Differential abundance analysis revealed higher relative abundances of Anaerostipes, Phocaeicola, and Collinsella in the gastric antrum of cancerous samples. Anaerostipes and Phocaeicola are typically enriched in the intestinal microbiota but are rarely observed in the stomach, suggesting their potential ecological and pathological relevance in gastric carcinogenesis. In H. pylori-negative patients, however, a different stage-associated abundance pattern was observed, in which Faecalibacterium, a genus predominantly associated with the intestinal environment, was less abundant in advanced gastric cancer samples than in earlier histological stages within the gastric body. These findings suggest that microbial changes during gastric cancer progression may follow different trajectories depending on H. pylori infection status. In oral samples, Haemophilus and Prevotella were more abundant in intestinal metaplasia than in low-grade dysplasia, and network analysis indicated links between Neisseria and Filifactor at oral and gastric sites. However, as the study population was limited to a single country and ethnicity, the applicability of these microbial markers should be carefully considered. Full article

Background: Metabolic syndrome, a clinical condition defined by central obesity, impaired glucose regulation, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol across the lifespan, is now a major public health issue typically managed with lifestyle, behavioral, and dietary recommendations. However, “one-size-fits-all” recommendations often yield modest, heterogeneous responses and poor long-term adherence, creating a clinical need for more targeted and implementable preventive and therapeutic strategies. Objective: To synthesize evidence on how the gut microbiome can inform precision nutrition and exercise approaches for metabolic syndrome prevention and management, and to evaluate readiness for clinical translation. Key findings: The gut microbiome may influence cardiometabolic risk through microbe-derived metabolites and pathways involving short-chain fatty acids, bile acid signaling, gut barrier integrity, and low-grade systemic inflammation. Diet quality (e.g., Mediterranean-style patterns, higher fermentable fiber, or lower ultra-processed food intake) consistently relates to more favorable microbial functions, and intervention studies show that high-fiber/prebiotic strategies can improve glycemic control alongside microbiome shifts. Physical exercise can also modulate microbial diversity and metabolic outputs, although effects are typically subtle and may depend on baseline adiposity and sustained adherence. Emerging “microbiome-informed” personalization, especially algorithms predicting postprandial glycemic responses, has improved short-term glycemic outcomes compared with standard advice in controlled trials. Targeted microbiome-directed approaches (e.g., Akkermansia muciniphila-based supplementation and fecal microbiota transplantation) provide proof-of-concept signals, but durability and scalability remain key limitations. Conclusions: Microbiome-informed personalization is a promising next step beyond generic guidelines, with potential to improve adherence and durable metabolic outcomes. Clinical implementation will require standardized measurement, rigorous external validation on clinically meaningful endpoints, interpretable decision support, and equity-focused evaluation across diverse populations. Full article

Triply Periodic Minimal Surface (TPMS) structures, with their zero average curvature, excellent energy absorption properties, high specific strength and high surface-to-volume ratio, could be used in a wide range of applications, such as the creation of lightweight and durable structures, grafts and implants. In this study, an internal TPMS structure inspiring trabecular bone and an external TPMS structure inspiring cortical bone were combined with infill density and topologically functionally graded to obtain hybrid structures. The aim of the study was to investigate the effects of functional grading on mechanical properties, energy absorption capacity and surface/volume (S/V) ratio and to determine the best combination. The novelty of the study is to obtain hybrid structures close to bone structures with a functional grading approach. The experimental design of the study was performed using the Design of Experiment (DoE) approach and the Taguchi method. Specimens were created according to the established experimental design and fabricated using a Masked Stereolithography (mSLA)-type 3D printer with bio-resin. The fabricated structures were subjected to compression tests; the results were examined in terms of deformation behavior, first peak, maximum force, energy absorption, specific energy absorption and S/V ratio. The optimal structures for defined input parameters were determined using signal-to-noise (S/N) ratios and ANOVA results. Deformations for diamond and primitive specimens began as shear band formation. Deformations for Neovius structures were mostly as brittle fracture. The highest first peak of 18.96 kN was obtained with the DN specimens, while the highest maximum force of 23.77 kN was obtained with the ND specimens. The best energy absorption property was also obtained with ND. The highest S/V ratio was 5.65 in the GP specimens. The statistical analyses were in accordance with the experimental results. Infill density increases decreased the S/V ratio while increasing all other parameters. This demonstrated the importance of mechanical-strength/porosity optimization for bone scaffold surrogate applications in this study. Full article

Background/Objectives: Breast cancer is the most common neoplasm among women and remains the leading cause of cancer-related mortality in the female population worldwide. Tumor cells exist within a highly oxidative microenvironment, which promotes the formation of substantial amounts of lipid peroxides. However, the clinical significance of circulating lipid peroxides in breast cancer is still not well understood. Methods: In this study, we quantified systemic lipid peroxide levels in plasma samples from 408 breast cancer patients and examined their associations with key clinicopathological parameters to evaluate their potential as disease biomarkers. Data are reported as relative light units (RLU). Results: Our findings revealed significantly higher lipid peroxide levels in HER2-amplified tumors compared with estrogen-receptor-positive tumors (1,133,494 ± 102,409 RLU vs. 951,883 ± 47,535 RLU; p = 0.0438). Elevated levels were also observed in patients with triple-negative breast cancer relative to those with Luminal A (1,163,323 ± 109,640 RLU vs. 875,633 ± 49,601 RLU; p = 0.0356) and Luminal B tumors (1,163,323 ± 109,640 RLU vs. 1,071,779 ± 98,329 RLU; p = 0.0254). In addition, increased lipid peroxidation was detected in patients with high-grade tumors (G3: 1,141,035 ± 101,045 RLU vs. G1–G2: 949,658 ± 46,119 RLU; p = 0.0346) and in those classified as at high risk of recurrence or death compared with low-risk patients (1,209,530 ± 95,396 RLU vs. 978,318 ± 229,526 RLU; p = 0.0054). Overweight patients also exhibited higher lipid peroxide levels than eutrophic individuals (1,131,233 ± 59,633 RLU vs. 820,772 ± 57,653 RLU; p = 0.0142). Conclusions: Collectively, these results suggest that circulating lipid peroxides may serve as potential biomarkers for recurrence and death risk in breast cancer, particularly among patients with more aggressive tumor phenotypes. Full article

Background and Objectives: This study evaluates the safety, tolerability, and efficacy of preservative-free Dorzolamide 2%-Timolol 0.5% (PF-DT), with a focus on improving the ocular microenvironment in a real-world transition setting. Materials and Methods: A prospective, multicenter, open-label study involving thirty patients with dry eye disease previously treated with BAK-DT was conducted. Participants were transitioned to PF-DT, and evaluated at weeks 4, 12, and 24. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included Break-Up Time (BUT), Schirmer test results, corneal staining, conjunctival hyperemia, intraocular pressure (IOP), and patient satisfaction. Results: Twenty-five patients completed the study. The OSDI improved from 21.5 to 12.5 (p < 0.001), with 60.0% of patients showing improvement and 52.0% achieving complete symptom resolution. Among eyes with corneal staining, 78.4% demonstrated a reduction of at least one grade, and 50.0% of those with conjunctival redness showed similar improvement. By week 24, 78.0% exhibited no corneal staining, and 50.0% had no conjunctival redness. BUT increased from 5.0 to 7.0 (p < 0.01), while IOP decreased by 1 mmHg (p < 0.01). Satisfaction regarding comfort (≥80%) and handling (≥50%) was high, with 88.0% preferring PF-DT. Conclusions: Transitioning to PF-DT improved ocular surface health while maintaining IOP control, supporting the benefits of preservative-free formulations in restoring microenvironment homeostasis and enhancing tolerability and patient satisfaction. Full article

Polyester fibers are extensively used in textiles, packaging, and industrial applications due to their durability and excellent mechanical properties. However, high-crystallinity polyester fibers represent a major challenge in plastic waste management due to their resistance to biodegradation. This study evaluated the biodegradation potential of environmental Bacillus isolates, obtained from mold-contaminated black bean plastic bags, toward polyethylene terephthalate (PET) and industrial-grade polyester fibers under mesophilic conditions. Among thirteen isolates, five (Bacillus altitudinis N5, Bacillus subtilis N6, and others) exhibited measurable degradation within 30 days, with mass losses up to 5–6% and corresponding rate constants of 0.04–0.05 day⁻¹. A combination of complementary characterization techniques, including mass loss analysis, scanning electron microscopy (SEM), gel permeation chromatography (GPC), and gas chromatography/mass spectrometry (GC/MS), together with Fourier-transform infrared spectroscopy (FTIR), thermogravimetric/differential scanning calorimetry (TGA/DSC), and water contact angle (WCA) analysis, was employed to evaluate the biodegradation behavior of polyester fibers. Cross-analysis of mass loss, surface morphology, molecular weight reduction, and degradation products suggests a surface erosion-dominated degradation process, accompanied by ester-bond hydrolysis and preferential degradation of amorphous regions. FTIR, TGA/DSC, and WCA analyses further reflected chemical, thermal, and surface property changes induced by biodegradation rather than directly defining the degradation mechanism. The findings highlight the capacity of mesophilic Bacillus species to partially depolymerize polyester fibers under mild environmental conditions, providing strain resources and mechanistic insight for developing low-energy bioprocesses for polyester fiber waste management. Full article

Effective drillhole placement is critical to the success of mineral exploration, particularly in brownfield settings where subsurface information remains sparse despite the availability of data from adjacent, previously explored areas. To address the challenges of uncertainty in resource estimation and the high cost of drilling, we present a drilling sequence optimization framework guided by geophysical and surface geochemical data. The framework integrates statistical learning and geostatistical simulation to construct a set of prior models of intrusion and nickel grade distribution. These models are used to quantify the expected reduction in uncertainty for each potential drillhole by evaluating their corresponding Efficacy of Information (EOI). This approach allows the sequential selection of drillhole locations that maximize information gain while managing exploration risk. We apply the methodology to a case study in the Curaçá Valley, Brazil, where prior data from a well-characterized nearby zone inform predictions in the adjacent target area. The results demonstrate that incorporating prior geological knowledge from nearby areas into the drilling strategy can significantly improve targeting efficiency and reduce uncertainty in early-stage brownfield exploration. Full article

Obesity, an escalating global health crisis, is characterized by adipose tissue hypertrophy and chronic low-grade inflammation. Although anti-obesity drugs can induce weight loss, their use is limited by adverse effects, underscoring the need for safer therapeutic strategies. In this study, we generated a recombinant form of Trichinella spiralis-derived macrophage migration inhibitory factor (rTs-MIF) and investigated its anti-inflammatory and anti-obesity effects via immunometabolic regulation. Male C57BL/6 mice fed a 45% high-fat diet were orally administered rTs-MIF, and its effects were evaluated by measuring fat mass, glucose metabolism, serum cytokines, liver histology, and adipose tissue parameters. In 3T3-L1 cells, we examined the effects of rTs-MIF on adipocyte differentiation, obesity-related gene expression, and intracellular signaling pathways. Oral rTs-MIF suppressed body weight gain, reduced fat mass, improved glucose levels, and decreased the food efficiency ratio. It also lowered pro-inflammatory cytokines and increased markers associated with M2 macrophages. In 3T3-L1 cells, rTs-MIF inhibited adipocyte differentiation and reduced the expression of lipogenic transcription factors and mouse Mif while modulating AKT and p44/42 MAPK signaling. These findings identify rTs-MIF as a potential bioactive candidate that ameliorates obesity by regulating the immune–metabolic axis. Full article

This work introduces ultrafast high-temperature graphitization (UHG) as an effective method to synthesize graphite with significantly reduced processing times of about 100 s and reduced consumed energy, as opposed to conventional methods that require several days at 2800 K. This novel process achieves graphitization of up to 90% within a few minutes due to the accelerated kinetics occurring at temperatures as high as 3400 K. Samples processed using UHG attained stable cyclic capacities of 350 mAh/g, which is fully comparable to commercially available graphite. Finite Element Simulations were also used to calculate the energy consumption for a scaled-up configuration, and it was found that the UHG approach reaches ultra-low energy consumption, requiring only 2.4 MJ/kg for the direct conversion of coke into graphite. By minimizing the duration of high-temperature processing and employing localized heating, UHG is envisioned to mitigate some of the challenges associated with traditional Acheson furnaces that have been in use for more than a century. Full article

Curcumin is a polyphenolic compound isolated from Curcuma longa, which is widely recognized for its therapeutic properties: particularly its strong anti-inflammatory and antioxidant activities. However, its practical incorporation into functional foods, especially aqueous dairy beverages, is severely hindered by its extremely low water solubility, poor chemical stability (notably at the near-neutral pH of milk), and very limited oral bioavailability. This review provides a critical synthesis of the literature published in the last two decades, with a focus on the development and application of food-grade oil-in-water (O/W) nanoemulsions to advanced colloidal delivery systems. It covers the fundamental principles of nanoemulsion formulation, including the selection of the oil phase, surfactants, and stabilizers, as well as both high-energy and low-energy fabrication techniques. It further examines the integration of these nano-delivery systems into dairy matrices (milk, yogurt, cheese), highlighting key interactions between nanoemulsion droplets and native dairy constituents such as casein micelles and whey proteins. Critically, findings indicate that nanoencapsulation not only enhances curcumin’s solubility but also protects it from chemical degradation during industrial processes, including pasteurization and sterilization. Moreover, the dairy matrix structure plays a key role in modulating curcumin bioaccessibility, with fortified products frequently exhibiting enhanced stability, shelf life, and sensory attributes. Finally, key technological challenges addressed the heterogeneous global regulatory landscape surrounding biopolymers and future trends: most notably, the growing shift toward “clean-label” biopolymer-based delivery systems. Full article

Background and Objectives: The treatment of duodenal injuries remains one of the most challenging issues in clinical surgery due to their high morbidity and mortality rates. The primary objective of this study was to evaluate the histopathology and other diagnostic outcomes of wound repair following surgical reconstruction of large experimental duodenal defects using synthetic (ePTFE, expanded polytetrafluoroethylene) or organic (JSP, jejunal serosal patch) materials. Materials and Methods: A total of 20 European rabbits were randomly divided into two equal groups (n = 10 each). A grade III defect covering over 50% of the duodenum’s circumference was created in the second part of the duodenum of the rabbits. The anesthesia, duodenal injury, postoperative care, and animal sacrifice protocols were identical for all experimental rabbits. The effectiveness of JSP and ePTFE patch repair techniques was investigated based on clinical, macroscopic, and microscopic assessments at two and four weeks postoperatively. Results: Survival rates were comparable between groups (p > 0.05). Remarkable mucosal regeneration was evident in all experimental animals by two weeks, showing complete coverage of the jejunal serosal and ePTFE patches by re-epithelialized mucosa with functional villus formation. While partial development of the underlying muscular and serosal layers was observed in both groups at four weeks, the JSP group achieved a significantly higher median histological score (19 vs. 14; p = 0.003). Conversely, the ePTFE group exhibited a major safety concern: a highly significant increase (p ≤ 0.001) in Grade 4 dense, inseparable adhesions throughout the abdominal cavity, which were entirely absent in the JSP group. Conclusions: Both JSP and ePTFE are viable for duodenal reconstruction, but the autologous JSP is superior in tissue healing and safety. Severe adhesions associated with ePTFE constitute a significant clinical concern, limiting its use to a second-line alternative. Consequently, JSP is the preferred option, while ePTFE requires further long-term safety validation. Full article