Search Results (59,536)

To clarify the effects of in situ tomato straw and green manure returning on soil quality and vegetable production in coastal saline–alkali greenhouse soils, this study employed a split-plot design to evaluate three green manure treatments (sweet corn, sorghum–sudangrass, and sesban) under two main treatments (tomato straw return or no straw return). The impacts on tomato and celery yield and quality, as well as soil physicochemical and biological properties, were assessed over a two-year rotation cycle. The results showed that: (1) compared to the control, green manure returning could significantly reduce soil bulk density, salinity, and fungal abundance; (2) different green manures specifically enriched functional microbes: Sesban enriched Nitrospira and Gemmatimonas; Sorghum–sudangrass enriched Streptomyces and Acidibacter; sweet corn enriched Pseudomonas; green manure reduced the relative abundance of Fusarium, whereas tomato straw showed the opposite trend; and (3) green manure, especially sorghum–sudangrass, significantly increased yields of both tomato and celery, while reducing celery cellulose content. Therefore, in situ sorghum–sudangrass returning is recommended as an effective strategy for maintaining soil health and achieving sustainable production in greenhouse systems within coastal saline–alkali regions. Full article

Systemic arterial hypertension (SAH) is a multifaceted condition marked by sustained elevations in arterial blood pressure. Its occurrence is closely related to alterations in target organs, such as the liver. Non-pharmacological treatments have been proposed for these effects. Thus, the aim of this study was to investigate the effects of açaí supplementation and resistance training, applied individually or in combination, on blood pressure and liver structural parameters. An experimental, quantitative, and longitudinal study was conducted using young Wistar rats (~60 days old) and spontaneously hypertensive rat (SHR) strains. Fifty rats were divided into five experimental groups: Wistar Control (C), Hypertensive Control (H), Hypertensive Trained (HT), Hypertensive Açaí-Supplemented (HA), and Hypertensive Trained plus Açaí Supplementation (HAT). Each group consisted of ten animals. Subsequently, analyses were performed for the antioxidant capacity and proximate composition of the açaí pulp, systolic blood pressure assessment, and histological evaluation of the liver. The açaí used exhibited high antioxidant capacity. At the end of the experimental period, the trained groups increased their maximal load carried, along with a reduction in systolic blood pressure in all treated groups. Açaí supplementation resulted in lower relative liver mass compared with the H group. The hypertensive condition promoted extracellular matrix expansion and a reduction in hepatocyte proportion. Both interventions attenuated these effects, and the combined treatment (HAT) produced the greatest improvement, indicating an additive response. Hypertension also elevated hepatic glycogen concentration, and the treatments reduced this alteration. It is concluded that açaí supplementation and resistance training could promote positive adaptations in the liver of hypertensive animals. Full article

Redevelopment precincts are often assessed through price uplift, although price appreciation alone does not show whether a local housing market becomes more active or liquid. This study examines whether residential turnover and property valuation diverged around the Etihad Campus redevelopment precinct in East Manchester after the 2014Q4 consolidation of the wider campus setting. Using Office for National Statistics House Price Statistics for Small Areas, the analysis applies a neighborhood-scale synthetic control design to a compact Core-4 treatment precinct, using a filtered within-Manchester donor pool to construct the synthetic benchmark. Residential turnover is measured as the mean residential sales count per Lower Layer Super Output Area (LSOA), and valuation is measured as the average of LSOA-level median house-price trajectories. Robustness is assessed using alternative treatment definitions and pre-intervention calibration windows. The results show a persistent post-2014 turnover shortfall relative to the synthetic benchmark, supported by rank-based placebo diagnostics and retained across all valid turnover specifications. By contrast, valuation evidence is weaker, mixed, and more sensitive to design choice. These findings indicate selective housing-market reconfiguration rather than generalized uplift. Redevelopment evaluation should therefore distinguish transaction circulation from price-based valuation, particularly in cumulative precinct-scale redevelopment settings. Full article

Adequate placental development and function, prerequisites for the development of a healthy fetus, rely on controlled trophoblast invasion into the decidua and remodeling of the spiral arteries. These tightly regulated processes involve epithelial–mesenchymal transition (EMT) and endovascular differentiation of trophoblast cells. Taxifolin (dihydroquercetin), a natural flavonoid with various pharmacological effects, previously showed cytoprotective, antioxidant, and anti-inflammatory activity on trophoblast cells. Given that the literature indicates that this flavonoid suppresses EMT and can affect angiogenesis across different cell types, we investigated the potential of taxifolin (10 and 100 µM) to modulate invasion and endothelial-like differentiation in human extravillous trophoblast HTR-8/SVneo cells by functional tests. Expression of different molecular markers relevant to these processes was evaluated at the mRNA and protein levels. Our results showed that taxifolin inhibited invasion of HTR-8/SVneo cells, involving downregulation of integrin α5 subunit and modulation of MMP-2 and MMP-9 mRNA expression and secretion. No changes in the concentrations of secreted TIMP-1 and TIMP-2 were observed following taxifolin treatment. Furthermore, downregulation of N-cadherin and vimentin in treated trophoblast cells indicated suppression of EMT. Taxifolin inhibited endothelial-like differentiation of HTR-8/SVneo cells, as evidenced by reduced tube formation and downregulation of VE-cadherin in treated cells. Moreover, expression of TGFB1 was upregulated in treated cells, as were levels of phosphorylated SMAD2/3, indicating involvement of TGF-β signaling in TF-induced effects on trophoblast cells. The in vitro effects of taxifolin on suppression of trophoblast invasion, EMT, and endothelial-like differentiation highlight its potential impact on placental development processes. Full article

Thai shallot (Allium cepa L. var. aggregatum) is rich in quercetin glycosides, which can be enzymatically hydrolyzed into aglycone forms with potentially higher bioavailability. However, whether this structural modification enhances metabolic efficacy in vivo remains unclear. This study aimed to compare the metabolic and histopathological effects of enzymatic (ESE) and non-enzymatic (NES) Thai shallot extracts in a high-fat diet (HFD)-induced obese mouse model. Male C57BL/6 mice were fed HFD for 12 weeks to induce obesity, followed by a 12-week treatment with NES or ESE (1000 and 2000 mg/kg/day). Metabolic parameters, lipid profiles, oxidative stress markers, hepatic enzyme activities, and histopathological changes were evaluated. Enzymatic hydrolysis significantly increased the proportion of quercetin aglycone without altering total quercetin content. Both NES and ESE improved fasting glucose, insulin resistance, lipid profiles, and oxidative stress markers compared with HFD controls. Histological examination showed attenuation of hepatic steatosis and preservation of tissue architecture in treated groups. However, no consistent superiority of ESE over NES was observed across metabolic or histopathological outcomes. Despite substantial modification of flavonoid composition, enzymatic processing did not enhance the measured metabolic efficacy of Thai shallot extract under the conditions tested. Because circulating quercetin and metabolite levels were not assessed, this finding should be interpreted as comparable metabolic efficacy rather than evidence of equivalent bioavailability. These findings suggest that factors beyond aglycone content may play a key role in determining biological activity, with implications for the development and cost-effectiveness of functional food products. Full article

Background/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p < 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p < 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p < 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p < 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p > 0.05). Conclusions: Our findings suggest that the CX3CL1–CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response. Full article

Acid mine drainage (AMD) pollution from closed coal mines in karst regions represents a major environmental challenge in the global mining industry. The complexity of hydrogeological conditions in such regions leads to significant challenges in both predictability and controllability of pollution. Taking the Yudong River Basin in Guizhou Province, Southwest China, as the study area, and based on six years (2017–2023) of systematic remediation practices and monitoring data, this study systematically evaluates the effectiveness and applicable conditions of three types of treatment technologies: centralized treatment stations, source control combined with end-of-pipe treatment, and water-sealing ecological plugging. On this basis, governance models applicable to karst regions are distilled. The results show that after six years of remediation, the number of pollution points in the Yudong River Basin decreased from 27 to 12. At the outflow section, the total Fe reduction rate reached 88.3%, the total Mn reduction rate reached 62.3%, and the proportion of contaminated river length was reduced by 78.5%. Each of the three technologies has its own applicable conditions. Centralized treatment stations, characterized by mature technology but high operational costs, are suitable for emergency transition periods. Source control combined with end-of-pipe treatment addresses both symptoms and root causes, making it applicable to complex pollution points. Water-sealing ecological plugging, although cost-controllable, carries a risk of secondary pollution in karst-developed areas. The failure of water-sealing ecological plugging technology is mainly attributed to two mechanisms: bypass flow through karst conduits and overflow induced by water level rise. Based on the six-year remediation practice, this study proposes a source control model for karst conduits centered on the core concepts of “filling, isolating, plugging, intercepting, draining, and controlling”. The implementation process consists of four stages: detailed investigation, graded optimization, stepwise implementation, and long-term monitoring. The core innovation lies in the cross-disciplinary application of coal mine water control techniques to environmental remediation, achieving a shift from passive end-of-pipe treatment to active source control. This model can provide theoretical reference and practical guidance for karst mining areas in Southwest China and other regions with similar geological conditions. Full article

Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate contemporary evidence regarding emerging and established treatment approaches for rosacea. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, and Web of Science were searched for studies published between 2016 and 2025. Original human studies evaluating therapeutic interventions for rosacea were included. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. Results: Fifteen studies involving 537 patients with rosacea and 77 controls (614 participants in total) met the eligibility criteria. Evaluated interventions included vascular-targeted therapies, topical anti-inflammatory agents, systemic and immunomodulatory treatments, and microbiome-oriented approaches. Oxymetazoline, pulsed-dye laser, platelet-rich plasma, ivermectin, azelaic acid, dapsone, sulfur preparations, and metronidazole demonstrated clinical benefits in reducing erythema, inflammatory lesions, or overall disease severity. Emerging therapies, including tofacitinib and oral ivermectin, showed promising results in refractory disease. Microbiome-related interventions, particularly Demodex-targeted therapies and Helicobacter pylori eradication, were also associated with clinical improvement. Risk-of-bias assessment identified two studies with low risk of bias, twelve with moderate risk of bias, and one study with high risk of bias. Conclusions: Current evidence supports a multimodal and mechanism-based approach to rosacea management, integrating vascular, inflammatory, immunological, and microbiological targets. However, the available evidence remains limited by small sample sizes, heterogeneous methodologies, short follow-up periods, and a predominance of non-randomized study designs. Large, well-designed randomized controlled trials are needed to establish optimal evidence-based treatment strategies and define the long-term efficacy and safety of emerging therapies. Full article

Opisthorchis viverrini (OV) is a liver fluke endemic to the Lower Mekong Basin. Infections often begin in childhood and are causally linked to cholangiocarcinoma, an often-fatal bile duct cancer. Anthelmintic treatment is the primary control strategy, but infection can recur. Therefore, additional strategies are needed. This study assessed the impact of “The Magic Glasses Opisthorchiasis” (MGO), a cartoon-based intervention, on schoolchildren’s OV-related knowledge, attitudes and practices (KAP). A cluster (school)-randomised controlled trial was conducted in Cambodia, Laos and Thailand. Clusters were randomised into either school health education only or with MGO. OV KAP was measured using a standardised questionnaire. FGDs and interviews were also conducted in intervention schools with schoolchildren, parents, and teachers. Cambodia intervention knowledge and attitude scores improved by 19.2 (p < 0.001) and 25.3 (p < 0.001) percentage points, respectively, relative to the control. Laos intervention knowledge and attitude scores improved by 19.0 (p < 0.001) and 14.2 (p < 0.001) percentage points. However, Thailand’s intervention knowledge and attitude scores declined by 23.3 (p < 0.001) and 15.8 percentage points (p < 0.001). There were no improvements in behaviour scores in any country, but parents and schoolchildren in Cambodia and Laos reported improved fish preparation practices, suggesting positive spillover effects from MGO. The findings support MGO as an effective tool for school-based health education. Full article

Managing vegetative vigor is a critical challenge for apple production in subtropical regions, where high water availability often promotes excessive canopy growth. This study evaluated the effects of split applications of prohexadione–calcium (ProCa) combined with naphthaleneacetic acid (NAA) and ethephon on the vegetative growth and yield performance of ‘Maxi Gala’ and ‘Fuji Suprema’ apples during the 2022/23 and 2023/24 growing seasons. The experimental design consisted of six plant growth regulator (PGR) protocols: a commercial standard (Control) with two applications, and five protocols based on six split applications initiated when fruit diameter reached ~8 mm, with 10-day intervals. The treatments included ProCa; ProCa + NAA; ProCa + ethephon; ProCa + NAA + ethephon; and ethephon + NAA. The ProCa + NAA protocol demonstrated the highest efficiency in vigor control, reducing shoot growth by up to 38% in ‘Maxi Gala’ and 65% in ‘Fuji Suprema’ relative to Control. Furthermore, this treatment enhanced fruit skin coloration, increased the proportion of Category 1 fruit, and improved return bloom and overall yield. These findings suggest that split applications of ProCa associated with NAA provide a robust strategy to optimize apple orchard productivity under the edaphoclimatic conditions of southern Brazil. Full article

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75% of renal cell carcinomas and is defined by near-universal VHL inactivation, leading to constitutive HIF stabilisation, metabolic reprogramming, and an immunologically distinct tumour microenvironment (TME). Although ccRCC is characterised by abundant immune infiltration, this paradoxically correlates with poor prognosis, reflecting a TME that imposes interconnected physical, immunological, and metabolic barriers to effective immunotherapy. Chimeric antigen receptor (CAR)-based therapies have revolutionised the treatment of haematological malignancies, but their translation to ccRCC has encountered substantial hurdles. The first-in-human trial targeting carbonic anhydrase IX (CAIX) was limited by on-target off-tumour toxicity and CAR immunogenicity—lessons that fundamentally reshaped the field. CD70 has since emerged as the dominant clinical target, expressed in over 80% of ccRCCs with a highly restricted normal tissue distribution. The phase I COBALT-RCC trial of CTX130, an allogeneic CRISPR-Cas9-edited CD70-directed CAR-T cell product, provided formal proof of concept, achieving disease control in 81.3% of heavily pretreated patients and a durable complete response now exceeding three years—the first such sustained remission reported for any CAR-T cell product in a solid malignancy. Nevertheless, the low frequency of durable responses and universal loss of CAR-T cell persistence by day 28 underscore that major barriers remain. Beyond CD70, the field has diversified across multiple platforms, including CAR–natural killer (NK) cells, CAR–natural killer T (NKT) cells, and CAR–macrophages, each offering distinct biological advantages. This review synthesises current knowledge of the ccRCC TME, the preclinical landscape of CAR-based therapies, and emerging clinical evidence from more than 30 registered trials. We discuss target antigens; engineering strategies to overcome TME barriers, including cytokine armouring, chemokine receptor co-expression, switch receptors, and metabolic reprogramming; and rational combination approaches. We argue that the convergence of optimised target selection, cellular engineering, combination strategies, and biomarker-driven trial design may ultimately improve outcomes for patients with ccRCC. However, achieving a cure remains an aspirational goal, and significant barriers must first be overcome. Full article

Background and Objectives: Seroma formation is the most common postoperative complication following mastectomy and axillary dissection, negatively affecting wound healing and delaying adjuvant therapy. Despite numerous surgical and pharmacological approaches, no universally effective strategies have been established. This study aimed to comparatively evaluate the effects of porcine dermal collagen (PDC), tranexamic acid (TXA), and thymoquinone (TQ) on seroma formation and tissue repair. Materials and Methods: A randomized controlled experimental study was conducted using 40 female Wistar albino rats that underwent modified radical mastectomy and axillary dissection. All surgical and postoperative procedures were performed in accordance with the institutional animal welfare and ethical guidelines, including postoperative analgesic administration. The animals were divided into four groups: control, PDC, TXA, and TQ (n = 10 each). Seroma volume was measured on postoperative day 14. Histopathological evaluation, immunohistochemical analysis (FGF2, VEGF, TGF-β1, p53), and quantitative real-time PCR were performed to assess tissue remodeling and molecular responses. Results: All treatment groups demonstrated a significant reduction in seroma volume compared to the control group, with the most pronounced decrease observed in the TQ and TXA groups (p < 0.0001), while PDC showed a moderate effect (p < 0.01). Histopathological analysis revealed increased collagen deposition and fibrin formation in the PDC and TQ groups, whereas TXA exhibited a more limited remodeling profile than the others. Immunohistochemical and molecular analyses showed significant upregulation of VEGF across all groups, with broader and more consistent increases in the PDC and TQ groups. TGF-β1 and FGF2 expression demonstrated region-specific increases, particularly in the thoracic tissue. p53 expression remained relatively stable in the TXA group but was elevated in specific regions in the PDC and TQ groups. Importantly, the increased inflammatory infiltration, edema, vascular proliferation, and fibrin deposition observed in the TQ group may reflect not only active tissue remodeling processes but also prolonged inflammatory activation and enhanced fibrotic responses and should therefore be interpreted cautiously. Conclusions: PDC, TXA, and TQ differentially modulate postoperative seroma formation via distinct biological mechanisms. While TXA primarily exerts a targeted anti-seroma effect and PDC enhances extracellular matrix stabilization, TQ is associated with broader angiogenic, inflammatory, and tissue remodeling responses within this preclinical rat model. These findings should be considered exploratory and hypothesis-generating, and additional mechanistic studies and clinical investigations are necessary before definitive therapeutic conclusions can be established regarding the use of TQ in human breast surgery settings. Full article

Antibiotic-resistant bacteria are widely distributed and threaten public health. Photocatalytic antimicrobial technology can effectively inactivate multidrug-resistant bacteria without readily inducing resistance. We previously showed that oxygen-rich vacancy Bi₂MoO₆ (OBM) exhibits excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), but the underlying molecular mechanisms remain poorly understood. Here, we employed integrated transcriptomics and metabolomics, with qRT-PCR validation, to systematically elucidate the antibacterial mechanism of OBM against MRSA. OBM treatment induced profound transcriptional and metabolic alterations: 231 differentially expressed genes and 206 differentially abundant metabolites were identified. Functional enrichment analysis revealed cooperative involvement in multiple critical pathways, including inhibition of amino acid biosynthesis and protein translation, disruption of cell wall and membrane integrity, induction of oxidative stress, collapse of energy metabolism (suppression of oxidative phosphorylation and impaired ATP synthesis), and imbalance in nucleotide metabolism (down-regulation of DNA helicase and mismatch repair genes, dysregulation of purine/pyrimidine metabolism). These findings demonstrate that OBM photocatalytically inactivates MRSA through a multi-target systemic attack at both the transcriptional and metabolic levels, providing a novel theoretical foundation for the development of photocatalytic materials aimed at controlling MRSA and other drug-resistant bacteria. Full article

Across the world’s electrical substations, water-treatment plants, and manufacturing lines, a single engineer with valid credentials and a laptop can today push new control logic to a programmable logic controller (PLC) and change the physical behaviors of safety-critical equipment within minutes. Firmware and ladder-logic updates on SCADA and industrial IoT systems are privileged operations: an attacker installing a malicious update controls the physical process. Existing protections concentrate install authority in a single party with no externally verifiable record; compromise of the vendor key, the engineering workstation, or any operator credential suffices to deliver an attacker-chosen payload to a PLC. CertiFlash binds every update to four independent approvals: a vendor signature, a FROST-Ed25519 threshold signature from an operator quorum, a per-session nonce from the PLC, and a monotonic counter. Every decision is recorded in an append-only Merkle transparency log. The PLC verifies the aggregate with a standard RFC 8032 Ed25519 verifier, requiring no FROST-specific device code. Four security properties (authenticity, authorization, rollback resistance, auditability) are machine-checked in Tamarin under a Dolev–Yao adversary with up to t − 1 compromised operators and corroborated through ten attack scenarios. The implementation runs with concurrent Modbus TCP and Siemens S7 traffic, blocks all attacks, signs in 27–192 ms (k = 3–10), keeps ML-DSA-65 within 6% of Ed25519 from 1 KiB to 10 MiB, and sustains 30.1 updates/s on 100 PLCs. The operator-quorum signature remains FROST-Ed25519: the design is partially post-quantum in the evaluated version. The framework maps to IEC 62443-3-3 SR 3.4 and NIS2 Article 21(2)(d–e). Full article

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with poor survival rates of late-stage disease. While immune checkpoint blockade (ICB) therapy has transformed treatment for mismatch repair-deficient (MMRd)/microsatellite instability-high (MSI-H) tumors, most CRC cases are mismatch repair-proficient (MMRp)/microsatellite-stable (MSS) and derive little to no benefit from current immunotherapy regimens. Tumor-associated macrophages (TAMs) constitute a significant component of the tumor microenvironment (TME) and exhibit a phenotypic gradient between pro-inflammatory (M1-like) and anti-inflammatory, immunosuppressive (M2-like) states. Although their polarization status is increasingly recognized as a key modulator of immunotherapy efficacy in CRC, a comprehensive synthesis of the literature regarding macrophage polarization and its relevance to improving CRC immunotherapy remains lacking. Methods: A systematic literature search was conducted across PubMed, EMBASE, and ScienceDirect from inception to December 2025 using terms encompassing macrophages, immunotherapy, immune checkpoint expression, colorectal cancer, and microsatellite stability status. Title, abstract, and full-text screening were performed independently by multiple authors. Sixty-five studies were included following PRISMA guidelines. The protocol was prospectively registered on PROSPERO (ID: CRD420251244320). Results: Three key themes were identified: (1) macrophage-mediated mechanisms of resistance to ICB, including M2 polarization driven by the PI3Kγ, STAT3, mTOR, and SIRT-1 axes, immunosuppressive cytokine production (IL-10, TGF-β), and altered immune checkpoint ligand expression; (2) macrophage polarization status and associated biomarkers as prognostic indicators of therapeutic response; (3) emerging macrophage-targeted therapeutic strategies in ongoing clinical trials, including CSF1R inhibitors, CD40 agonists, CD47/SIRPα blockade, and STING agonists. Conclusions: TAM polarization is a critical determinant of immunotherapy resistance and patient prognosis in CRC. Macrophage-targeted strategies, particularly M2-to-M1 repolarization approaches used in combination with existing ICB regimens, represent a promising avenue for expanding immunotherapy efficacy beyond MSI-H disease. Further translational research and randomized controlled trials are needed to validate these targets clinically. Full article