Search Results (10,651)

Oncolytic coxsackievirus B3 (oCVB3) strain PD-H has shown potent oncolytic efficacy and a remarkable safety profile in the treatment of colorectal cancer in vivo after intratumoral (i.t.) injection. In this study, we investigated the safety and efficiency of PD-H following intravenous (i.v.) virus administration. When injected i.v. into Balb/C mice bearing subcutaneous Colon-26 tumors, PD-H led to slightly reduced tumor progression and a significant increase in animal survival, but it also caused multi-organ infection and tissue damage. To improve the safety profile of PD-H, we inserted microRNA target sites (miR-TS) of the heart-specific miR-1, pancreas-specific miR-375, liver-specific miR-122, and brain-specific miR-124 or the tumor-suppressor miR-145 into the genome of PD-H and generated the viruses PD-622TS and PD-145TS. Both viruses replicated similarly and induced cytotoxicity comparable to that of PD-H in the colorectal carcinoma cell lines Colon-26 and CT-26Luc. Their replication was inhibited in HEK293T cells transiently transfected with the cognate microRNAs. In vivo, i.v. administration of PD-145TS and PD-622TS to healthy Balb/C mouse resulted in significantly lower viral titers in the organs of mice and led to significantly less-intense pathological alterations compared to PD-H. PD-622TS injected i.v. into Balb/C mice with CT-26Luc-induced peritoneal carcinomatosis did not induce off-target alterations in normal organs, but it failed to induce a therapeutic effect. These data indicate that PD-H or microRNA-regulated PD derivatives exhibit only limited therapeutic efficacy following i.v. injection in colorectal tumor-bearing mice. However, the newly engineered microRNA-regulated PD-H variants demonstrate improved safety profiles. Full article

The valorization of dredged sediments represents a major environmental and logistical challenge, particularly in the context of forthcoming regulations restricting their marine disposal. This study investigates the potential of untreated dredged sediments as sustainable raw materials for geopolymer binder development, with the dual objective of sustainable sediment management and reduction in cement-related environmental impact. Dredged sediments from the Grand Port Maritime de Bordeaux (GPMB) were activated with sodium hydroxide (NaOH) and sodium silicate (Na₂SiO₃), both alone and in combination, with supplementary aluminosilicate and calcium-rich co-products, to assess their reactivity and effect on binder performance. A multi-scale experimental approach combining mechanical testing, calorimetry, porosity analysis, Scanning Electron Microscopy and Energy-Dispersive Spectroscopy (SEM–EDS), X-ray diffraction (XRD), Thermogravimetric Analysis (TGA), and solid-state Nuclear Magnetic Resonance (NMR) was employed to challenge the commonly assumed inert behavior of sediments within geopolymer matrices, to elucidate gel formation mechanisms, and to optimize binder formulation. The results show that untreated sediments actively participate in alkali activation, reaching compressive strengths of up to 5.16 MPa at 90 days without thermal pre-treatment. Calcium-poor systems exhibited progressive long-term strength development associated with the formation of homogeneous aluminosilicate gels and refined microporosity, whereas calcium-rich systems showed higher early age strength but more limited long-term performance, linked to heterogeneous gel coexistence and increased total porosity. These findings provide direct evidence of the intrinsic reactivity of untreated dredged sediments and highlight the critical role of gel chemistry and calcium content in controlling long-term performance. The proposed approach offers a viable pathway for low-impact, on-site sediment valorization in civil engineering applications. Full article

The presence of the brittle β/B2 phase in TiAl alloys often deteriorates their mechanical properties, posing a significant challenge for manufacturing large-sized, high-performance sheets. To address this issue, this study systematically investigates the synergistic effect of pack rolling and subsequent heat treatment on the microstructure evolution and mechanical properties of a Ti-44Al-4Nb-1.5Mo-0.1B-0.1Y alloy. Sheets with two different deformation levels (R7: 69.8% and R11: 83.0% reduction) were prepared via pack rolling. This was followed by a series of heat treatments at different temperatures (1150–1350 °C) and cyclic heat treatments at 1250 °C (3, 6, and 9 cycles). The results demonstrate that the higher deformation level (R11) promoted extensive dynamic recrystallization, resulting in a uniform microstructure of equiaxed γ, α₂, and β phases, while the lower deformation (R7) retained a significant fraction of deformed γ/α₂ lamellae. Heat treatment at 1250 °C was identified as optimal for transforming the microstructure into fine lamellar colonies while effectively reducing the β/B2 phase. Cyclic heat treatment at this temperature further decreased the β-phase content to 4.1% after 9 cycles. The elimination mechanism was determined to follow the β→ α → γ + α₂ phase transformation sequence, driven by the combined effect of rolling-induced defects and cyclic thermal stress. Cyclic heat treatment at this temperature was particularly effective in generating a high density of nucleation sites within the lamellar colonies, leading to significant refinement of the lamellar structure. Consequently, the R11 sheet subjected to 9 cycles of heat treatment exhibited a 15.5% increase in tensile strength and an 8.3% improvement in elongation compared to the hot-isostatically pressed state. This enhancement is primarily attributed to the significant refinement of lamellar colonies and the reduction in interlamellar spacing. This work presents an effective integrated processing strategy for fabricating high-performance TiAl alloy sheets with superior strength and toughness. Full article

Background: Diffuse large B cell lymphoma is an aggressive, heterogeneous yet treatable disease. Primary bone lymphoma is a lymphoma involving a single or multiple osseous sites with or without regional nodal involvement. It is exceedingly rare, representing <1% of new non-Hodgkin lymphoma cases per year. Most cases of primary bone lymphoma are diffuse large B cell lymphoma. They infrequently involve the craniofacial bones and mandible; its rarity can lead to delays in diagnosis. Case Series Presentation: Two 64-year-old male patients initially presented to local dentists with concerns of tooth pain and numbness. Both underwent extensive dental procedures including extraction and debridement, with an initial diagnosis of osteomyelitis. They were placed on long-term antibiotics. After months without improvement, further testing was pursued, including imaging and repeat biopsies. The patients were finally diagnosed with primary bone diffuse large B cell lymphoma. From the initial treatment of osteomyelitis, a median time of 8.5 months passed before diagnosis of lymphoma. Treatment with cytotoxic chemotherapy was initiated and both patients achieved remission. Conclusions: As in the two cases presented here, the initial point of entry into the medical system may be a visit to the local dentist. When patients present with periodontal complaints, it is imperative to maintain a broad differential, including lymphoma. This is especially crucial when the patient’s clinical course does not respond to initial treatment. This results in delays of diagnosis and initiation of therapy for a treatable cancer. Full article

Background: Hyaluronic acid (HA) injections have become a cornerstone of minimally invasive aesthetic medicine. While the demand for these procedures continues to grow globally, large-scale longitudinal analyses of patient demographics and specific injection site trends remain limited, particularly in Asian populations. Existing data in Japan are largely confined to aggregate procedure numbers. This study aimed to elucidate the transition in patient demographics and site-specific treatment trends using a nationwide big-data approach. Methods: This retrospective study analyzed 299,413 treatment sessions (417,590 injection sites) from patients who underwent facial HA injections at 110 clinics across Japan between October 2020 and December 2024. Data were analyzed by year, patient age, and injection site to evaluate demographic shifts and treatment patterns. Results: The annual number of treatment sessions increased steadily during the study period. A significant demographic shift was observed: while patients in their 20s were predominant in 2020–2022, the proportion of patients aged ≥ 40 years increased markedly from 2023 onward, accounting for more than half of all cases (63.7% in 2024). Treatment preferences varied distinctly by age; younger patients favored localized contouring (e.g., pretarsal fullness, chin), whereas older patients required multi-site rejuvenation. By 2024, the orbital rim became the most frequently treated site (22.6%). Statistical analysis confirmed that age was a significant predictor for multi-site treatments (p < 0.001). Conclusions: This large-scale analysis reveals a clear transition in the Japanese aesthetic market from contour enhancement in younger demographics to anatomy-based rejuvenation in middle-aged and older populations. Full article

Nicotinic acetylcholine receptors (nAChRs) are membrane-bound proteins that mediate fast synaptic transmission throughout the nervous system. A functional nAChR subtype is formed by the combination of multiple subunits arranged as homomeric or heteromeric pentamers, each with a distinct pharmacological profile. Disruption of their neurotransmission contributes to various neuropathologies, emphasizing the need for detailed knowledge of receptor structure, function, subunit composition, dynamics, and potential ligand-binding sites. However, their structural complexity as integral membrane proteins has hindered expression in mammalian cell lines and proven even more challenging to crystallize, limiting insights into ligand interactions. Understanding the molecular determinants governing nAChRs function is essential for the rational design of selective therapeutics targeting neurological disorders. The emergence of a chimeric receptor approach has dramatically improved the ability to study these important proteins and opened new avenues for high-throughput screening in drug discovery efforts. This review explains how the design of chimera constructs using soluble homologs, such as AChBP, provides researchers with an immense opportunity to investigate receptor structure–function relationships and subtype-specific properties, thereby facilitating the development of more effective treatments. Full article

Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients. Full article

Dihydroartemisinin (DHA), a first-line treatment for uncomplicated malaria, has demonstrated antitumor activity against a variety of human cancers, emphasizing its potential for repurposing as an anticancer agent. However, its short half-life and poor bioavailability hinder its application in cancer therapy. We previously demonstrated that the molecular hybridization of DHA with bile acids (BAs) enhances its anticancer activity by improving stability and reducing toxicity. Based on this rationale, here, we designed and synthesized a library of DHA-based hybrids through conjugation with ursodeoxycholic and chenodeoxycholic bile acids. Different conjugation sites and both cleavable and non-cleavable linkages were explored to enable a comprehensive structure–activity relationship analysis. The resulting BA-DHA hybrids were evaluated in vitro for their anticancer activity against HCT116 and RKO colorectal cancer cell lines. As a result of the synergistic effect of the linker type and conjugation site, the BA-DHA hybrids synthesized via click chemistry emerged as the most active compounds in both cell lines, displaying 2- to 20-fold higher activity than the parent DHA. Mechanistic investigations further revealed that the click-derived BA-DHA hybrids possess enhanced anticancer activity and antimetastatic potential, achieving comparable or even superior efficacy to the parent compound at markedly lower concentrations. Full article

Objective: The emergence and spread of multi-drug-resistant (MDR) bacteria pose a growing threat in veterinary medicine, particularly in equine hospitals. This study investigated the colonization and infection dynamics of horses undergoing emergency laparotomy with two distinct antibiotic protocols (single-shot versus 5-day protocol) during hospitalization. Methods: Nasal swabs and fecal samples were collected from 67 horses undergoing emergency laparotomy at clinic admission as well as on postoperative days 3 and 10. These were screened for multi-drug-resistant indicator pathogens. As multi-drug-resistant indicator pathogens, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E), and bacteria belonging to the Acinetobacter baumannii complex were defined. Results: Preoperatively, 6.2% of horses tested positive for MRSA and 13% for ESBL-E. An increase in colonization was observed on day 3 postoperatively, with 62.1% of nasal swabs and 86.4% of fecal samples testing positive for MDR organisms. On day 10, 53.4% of nasal swabs and 62.5% of fecal samples tested positive for indicator pathogens. Surgical site infection developed in five horses, two of which tested positive for MRSA in both nasal and wound samples during hospitalization, supporting the potential role of nasal carriage as a source of infection. Furthermore, all horses tested positive for ESBL-E during at least one time-point during hospitalization, and Enterobacterales (MDR in two surgical site infections (SSI)) were involved in all surgical site infections. No significant differences were observed between the two antibiotic treatment groups regarding colonization rates with indicator pathogens during hospitalization. However, the results indicate that hospitalization itself contributes to increased colonization with resistant bacteria. A clear limitation of the study is the restricted number of sampled horses and the lack of environmental contamination data. Non-sampled hospitalized horses with and without antibiotic treatment may have acted as reservoirs for MDR bacteria. Conclusion: The findings emphasize the need for routine environmental monitoring and strict adherence to hygiene protocols in equine clinics to reduce the risk of nosocomial transmission. Ongoing surveillance and infection control strategies are essential to mitigate the spread of MDR pathogens in veterinary settings. Full article

To address the challenge of low nitrogen removal efficiency, particularly the difficulty in meeting total nitrogen (TN) discharge standards during low-temperature seasons and intermittent emission modes in conventional aquaculture wastewater treatment, this study proposed the novel application of bioretention systems. Biochar and sponge iron were used as fillers to construct three bioretention systems: biochar-based (B-BS), sponge iron-based (SI-BS), and a composite system (SIB-BS), for evaluating their nitrogen removal performance for aquaculture wastewater treatment. Experimental results demonstrated that under intermittent flooding conditions at 8.0–13.0 °C and increasing TN loading (9.48 mg/L–31.13 mg/L), SIB-BS maintained stable TN removal (79.7–86.7%), outperforming B-BS and SI-BS (p < 0.05). Under continuous inflow (influent TN = 8.4 ± 0.5 mg/L) at 8.0–13.0 °C, SIB-BS achieved significantly lower effluent TN (2.57 ± 1.5 mg/L) than B-BS (5.6 ± 1.6 mg/L) and SI-BS (5.0 ± 1.5 mg/L) (p < 0.05). Meanwhile, when the temperature ranged from 8.0 to 26.3 °C, SIB-BS exhibited a more stable and efficient denitrification ability. Mechanistic investigations revealed that coupling biochar with sponge iron promoted denitrifying microbial activity and enhanced the functional potential for nitrogen transformation (p < 0.05). Specifically, biochar provided porous attachment sites and improved mass transfer, while sponge iron supplied readily available Fe²⁺ as an electron donor; their combination buffered iron oxidation and facilitated Fe²⁺-mediated electron transfer. At low temperature, SIB-BS further stimulated extracellular polymeric substances (EPS) secretion, strengthened biofilm stability without causing blockage, and improved the protective interactions between fillers, thereby increasing metabolic efficiency and sustaining TN removal under variable loading. This study provided a technical reference for the efficient denitrification of aquaculture wastewater. Full article

Soil total carbon (TC) and total nitrogen (TN) are key indicators of soil fertility and ecosystem stability, particularly in dryland agroecosystems. However, how rotational tillage combined with straw return affects aggregate formation and aggregate-associated TC and TN stabilization remains insufficiently understood. In this study, we aimed to clarify how rotational tillage affects aggregate structure, stability, and the spatial distribution of TC and TN, thereby revealing internal processes driving nutrient stabilization in dryland farming systems. A long-term field experiment was conducted at the Shenfeng site of Shanxi Agricultural University, China, including three rotational tillage systems with straw return: T1 (two years of no tillage (NT) + one year of deep tillage (DT)), T2 (two years of conventional tillage (CT) + one year of DT), and T3 (two years of DT + one year of CT). Soil aggregates were separated into total mechanical aggregate (TMA), 0.25–2 mm MA, and 2–10 mm MA, and they were further fractionated into water-stable aggregates (WM, Wm, and Wf) for TC and TN analysis. The results showed that aggregate stability, TC, and TN were positively correlated and decreased with soil depth, indicating strong surface enrichment. TC was mainly enriched in 0.25–2 mm MA, whereas TN was concentrated in 2–10 mm MA, and water-stable macroaggregates (WM) acted as the dominant reservoirs for R_C and R_N. Relative to the 2016 baseline (CK), TC in 2022 tended to be higher under rotational tillage with straw return, while NT-containing systems better maintained TN across the 0–60 cm profile. Among the treatments, T1 provided the most balanced performance, with a higher MWD and GMD, lower D, and improved aggregate-associated TC and TN retention. These findings suggest that rotational tillage with straw return, particularly the NT–NT–DT sequence, can support aggregate stability and is associated with improved aggregate-mediated TC and TN retention in the Loess Plateau dryland winter wheat system. Full article

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article

Diabetes mellitus encompasses a heterogeneous group of metabolic disorders defined by abnormalities in insulin secretion, function, or both. Exogenous insulin therapy has long been the principal treatment strategy for patients with type 1 diabetes and for those in advanced stages of type 2 diabetes. Stem cell therapy has gained significant attention in recent years as a potential curative approach for several life-threatening disorders. In this review, we focus on the use of induced pluripotent stem cells as an alternative source for beta-cell generation, offering a solution to organ scarcity and providing a sustainable supply of insulin-producing cells. We further evaluate current developments in encapsulation technologies and transplantation sites, while noting that the issue of immune-mediated graft rejection continues to be widely debated. The aim of this review is to outline encapsulation techniques and transplantation approaches explored in animal models, and to discuss the risks and challenges anticipated in human clinical trials. Full article

Background/Objectives: The study aimed to characterize perioperative complications and their relationship with nutritional risk in gastrointestinal cancer patients undergoing surgical treatment. Methods: An observational, prospective, and multicenter study was carried out in 469 patients with gastrointestinal malignancies undergoing elective major abdominal surgical procedures in public hospitals throughout Spain. Complications developed during hospitalization and at 30 days after surgery were recorded, and the patients’ nutritional status was evaluated using the MUST screening tool. Results: Colorectal and gastric cancer were the most common tumors. Complications during hospitalization occurred in 146 patients (rate 31.1%). Infections accounted for 68.5% of complications, in particular surgical site infections (SSIs), followed by paralytic ileus (40.4%). At 30 days, the complication rate was 9%, with infections as the most common events. In patients with severe nutritional risk at discharge (MUST score ≥ 2), the percentage of patients with complications was 24.7% as compared to 9.2% in patients without complications (p < 0.0001). Conclusions: Clinicians should be aware of the high frequency of SSIs and that complications are higher among patients with severe nutritional risk. These findings emphasize the need for routine nutritional screening and targeted perioperative support in cancer patients undergoing gastrointestinal cancer surgery. Full article

Background: Gastric cancer (GC) is one of the most common malignancies, requires aggressive treatment, as has a high incidence of complications. The high prevalence of cachexia and comorbidity among GC patients has led to the development of the “prehabilitation” concept. We aimed to investigate the prognostic value of cachexia in the “Western” patient population with resectable GC and to evaluate its utility as an indicator for a home-based prehabilitation program. Methods: This cohort study included 147 patients who underwent surgical treatment for GC from 2019 to 2023. A multivariable analysis was conducted to study the impact of cachexia on postoperative outcomes in 122 patients with resectable GC. The prehabilitation group included 25 patients with cachexia who underwent a 2-week-long multimodal prehabilitation program prior to surgery. The functional results, as well as the 30-day incidence of postoperative complications and 90-day mortality, were evaluated. Results: There were 76 (51.7%) patients with cachexia. Multivariate analysis revealed that cachexia was a significant predictor of all postoperative complications (OR = 5.48, 95% CI 1.85–18.39, p = 0.001), severe postoperative complications (OR = 15.87, 95% CI 3.05–131.81, p < 0.001) and surgical site infection (SSI) (OR = 8.03, 95% CI 1.89–49.09, p = 0.038). Patients in the prehabilitation group had a lower incidence of SSI than in the control group (8.3% vs. 23.5%, p = 0.049). Conclusions: Preoperative cachexia is a potentially modifiable predictor of complications after gastric cancer surgery, and its identification may help define high-risk patients for proactive multimodal prehabilitation. Full article