Search Results (1,079)

Background: Highly pathogenic avian influenza (HPAI) poses a critical global threat to both the poultry industry and public health. Although Morocco currently maintains HPAI-free status, the country faces substantial risk due to its location along major migratory flyways and its extensive commercial trade networks within the poultry sector. Available data indicate that the links between live bird markets, production farms, and related facilities in the poultry sector constitute a pivotal determinant of disease epidemiology. This study aimed to analyze these movements and determine how they can influence the spread of the disease and to guide policymakers in developing effective risk-based surveillance and control strategies tailored to the local context.: A questionnaire-based cross-sectional survey was conducted across the Casablanca-Settat region, including nine provinces and 138 municipalities, to investigate the movement patterns within the poultry sector in this region. Social network analysis (SNA) was employed to construct a movement network, and findings were spatially visualized using Geographic Information Systems (GIS) and analyzed through network analysis in R.: A total of 945 transport routes were recorded in 126 municipalities. Centrality measures identified three predominant network nodes exhibiting high degree and betweenness centrality values. Our findings indicate that although the network has a low density, the transmission of IAHP remains critical due to frequent bidirectional links and a heterogeneous network structure. The high concentration of movements by a few “hub” municipalities leads to an early emergence and rapid dissemination.: The identification of highly influential nodes allows veterinary authorities to prioritize and target surveillance activities toward municipalities with the greatest likelihood of disease introduction or persistence. The network’s structural connectivity suggests a theoretical potential for rapid HPAI spread, underscoring the importance of the frequent bidirectional links identified between municipalities. This protects both Morocco’s poultry industry and public health. Full article

Developing cost-effective photocatalysts with high activity remains a key challenge in photocatalysis. In this study, a low-cost nickel phosphide (Ni₂P) cocatalyst was combined with MIL-53(Fe) to fabricate Ni₂P/MIL-53(Fe) nanocomposites via a simple hydrothermal method. The as-prepared composites were systematically characterized by XRD, FT-IR, SEM, UV-vis DRS, PL, and EIS to evaluate their structural, morphological, optical, and electrochemical properties. The introduction of Ni₂P significantly promoted the separation of photogenerated electron–hole pairs on the MIL-53(Fe) surface, thereby enabling valence band holes (h⁺) to participate in alcohol oxidation, as confirmed by photoelectrochemical analysis. Under optimized conditions, the Ni₂P/MIL-53(Fe) nanocomposite achieved a significant photocatalytic alcohol conversion rate of 74%, which is 7.4-fold and 2.5-fold higher than those of pristine Ni₂P and MIL-53(Fe), respectively. Furthermore, mechanistic studies revealed that valence band holes are primarily responsible for the selective oxidation of aromatic alcohols. Full article

Introduction: PKMYT1 is a WEE-family G2/M cell cycle checkpoint kinase commonly overexpressed in a broad spectrum of human malignancies. WEE1 exclusively phosphorylates CDK1 at Tyr15, whereas PKMYT1 targets both Thr14 and Tyr15. Unlike WEE1 inhibition, PKMYT1 suppression triggers synthetic lethality with CCNE1. Nearly all disclosed PKMYT1 inhibitors so far fall into structural analogs originating from RP-6306, making the discovery of PKMYT1 inhibitors with chemotypes distinct from RP-6306 crucial. Methods: The compounds were structurally optimized using CADD, synthesized, and characterized by ¹H NMR, ¹³C NMR, HRMS, and HPLC. They were then assessed for kinase binding affinity via the LanthaScreen^TM Eu kinase binding assay, for cellular activity using the CCK-8 assay, and for cell-cycle distribution by flow cytometry, along with investigations into related mechanisms. Results: This study yielded 24 compounds of 2-aminopyrimidine through substituent derivatization of the pyrimidine scaffold. Among these derivatives, MS13 exhibited potent kinase binding affinity against PKMYT1 (IC₅₀ = 0.86 nM) and demonstrated strong anti-proliferative activity against CCNE1 high-amplification OVCAR3 cells and HCC1569 cells (IC_50-OVCAR3 = 1.52 μM, IC_50-HCC1569 = 0.66 μM). Additionally, it showed some selectivity towards A549 and HEK293T cells, with SI values of 4.31 (A549/OVCAR3), 9.92 (A549/HCC1569), 2.04 (HEK293T/OVCAR3), and 4.70 (HEK293T/HCC1569). Compound MS13 dose-dependently suppressed clonogenicity and triggered S-phase cell cycle blockade. Pharmacokinetic studies showed moderate hepatic microsomal stability (t_1/2 = 32.2 min). Molecular dynamics simulations indicated a favorable binding mode between compound MS13 and PKMYT1 (docking score: −9.322 kcal/mol). Conclusions:MS13 is a promising highly potent tool compound that provides a clear direction for the future optimization of PKMYT1 inhibitors. Full article

The thieno[3,2-d]pyrimidine scaffolds have emerged as an important class of heterocycles in anticancer drug discovery, with clinically advanced drugs olmutinib and pictilisib highlighting their therapeutic potential. This review presents thieno[3,2-d]pyrimidine-containing anticancer agents reported between January 2008 and August 2025, focusing on synthetic methodologies, anticancer-related biological activities, and structure–activity relationships. Thieno[3,2-d]pyrimidine derivatives have been investigated as inhibitors of numerous cancer-related targets, including EGFR, PI3K/mTOR, CDKs, JAK, VEGFR, HDAC, ATR, and other oncogenic proteins. This review also summarizes thieno[3,2-d]pyrimidine scaffolds with anticancer activity, with particular emphasis on the design and synthesis of lead compounds, molecular hybridization strategies, and recent advances in this area. Synthetic pathways for lead compounds are systematically presented and discussed, along with pharmacophoric features. In addition, detailed structure–activity relationship analyses are provided to highlight the influence of heterocyclic fusion, linker optimization, hydrogen-bonding motifs, electronic effects, hydrophobic fragments, and the introduction of hybrid scaffolds on antiproliferative potency, kinase inhibition, selectivity, and multitarget activity. In addition, this review demonstrates the significant potential of thieno[3,2-d]pyrimidine-based scaffolds as a privileged platform for the development of next-generation targeted anticancer agents and offers valuable guidance for future medicinal chemistry research. Full article

The limitations of conventional inorganic electrodes call for organic alternatives for advanced energy storage. Metal–covalent organic frameworks (MCOFs) integrate the metal active sites of metal–organic frameworks (MOFs) with the high chemical stability imparted by strong covalent bonds in covalent organic frameworks (COFs) while retaining the high specific surface area and tunable porosity of both material classes. Among these, MCOFs constructed from porphyrin and phthalocyanine building units have emerged as a research hotspot in electrochemical energy storage owing to their inherent 18π-conjugated macrocyclic electronic systems, well-defined M–N₄ coordination sites, and potential bipolar charge storage characteristics. This review systematically summarizes recent advances in this class of materials. First, from the perspective of metal center introduction timing, three core synthetic strategies—pre-metallation, simultaneous metallation, and post-metallation—are categorized and evaluated in terms of coordination precision, synthetic efficiency, and scalability potential. Second, the regulatory effects of two-dimensional layered and three-dimensional interpenetrated structures on charge transport pathways and structural stability are elucidated. Subsequently, the applications of porphyrin/phthalocyanine-based MCOFs in lithium-based batteries, zinc-based batteries, sodium/potassium-ion batteries, and supercapacitors are reviewed in detail, with emphasis on the key roles of metal active sites in catalytic conversion, chemical anchoring/confinement, interface stabilization, and pseudocapacitive contribution. Finally, future directions to address key performance and mechanistic bottlenecks are discussed. This review aims to provide a systematic reference for the rational design and energy storage applications of high-performance porphyrin/phthalocyanine-based MCOFs. Full article

The introduction of Joint Clinical Assessments (JCAs) under the European Union Health Technology Assessment Regulation (EU HTAR) represents a major structural reform aimed at reducing fragmentation and duplication in clinical evidence assessment across Member States. While JCAs are intended to support national health technology assessment (HTA) processes through a common EU-level clinical evaluation, their integration into established national HTA and reimbursement systems remains untested at this early stage of implementation. This paper reports findings from two surveys conducted in 2025 among local affiliate representatives with expertise in relevant HTA and market access activities across 25 European countries (comprising 24 EU Member States and Norway), capturing early national perspectives on key aspects of JCA implementation. The surveys explored anticipated impact on national reimbursement timelines, current opportunities for early HTA advice and PICO input, approaches to handling post-JCA data availability, and nationally prioritised policy and implementation issues. Results indicate mixed expectations regarding the potential impact of JCA on reimbursement timelines, with perceived risks of delay largely viewed as possibly transitional and mitigable through national process adaptation. Respondents emphasised the importance of transparency in PICO consolidation and clarity on the use of JCA reports in national appraisals. Overall, the findings suggest that JCA may represent a reconfiguration rather than a centralisation of evidence assessment, with national influence exercised earlier in the assessment lifecycle. These insights provide policy-relevant input to inform ongoing EU HTA implementation and future refinement of the JCA framework. Full article

In the present work, polyvinylpyrrolidone (PVP) was selected as the primary raw material and fully dissolved in N,N-dimethylformamide (DMF) solvent. Hydroxymethyl cellulose (HMC), acrylic acid (AA) monomer with outstanding chelating performance, and UR were added in sequence. On this basis, composite nanofiber membrane substrates of PVP/AA/HMC/UR were fabricated by means of electrospinning. Afterwards, silane coupling agent KH-560 was blended with polylactic acid (PLA). A uniform PLA/KH-560 functional coating was covered on the surface of the as-prepared nanofiber membrane via microfluidic coating treatment, and the target composite nanofiber adsorbent was ultimately obtained. Relevant performance characterization results indicated that moderate addition of HMC could greatly optimize the tensile strength of the membrane material, whereas excessive HMC dosage would cause a deterioration in mechanical strength. Moreover, the breaking elongation presented a slight declining trend, and the integrated mechanical stability of the membrane could fully meet the service demands for cyclic reuse. As a functional monomer, acrylic acid effectively boosted the material’s adsorption performance toward typical heavy metal ions, including Zn²⁺, Cu²⁺ and Pb²⁺. In simulated acidic wastewater generated from rare earth mining and extraction (pH = 3 and pH = 6.5), the removal efficiency of the as-prepared material for the three heavy metal ions all exceeded 95%. Even after being soaked in strong acid solution at pH 2 for 8 h, its adsorption rate was still maintained at 88.5%. In the cyclic experiment, the adsorption efficiency stayed above 75% after two recycling runs, decreased to roughly 55% in the third cycle, and dropped below 30% at the fourth reuse stage. The introduction of UR imparted remarkable acid-resistant structural stability to the composite material. The membrane structure remained complete without damage after long-term immersion in a pH 2 strong acid environment, and high-efficiency heavy metal removal capability could be guaranteed when the solution pH was not lower than 3. Targeting the practical treatment dilemma of acidic heavy metal-containing wastewater from rare earth exploitation and extraction, this research successfully developed a novel eco-friendly adsorbent featuring superior acid resistance, high adsorption performance and certain recyclability. This newly designed material makes up for the deficiencies in traditional adsorbents represented by activated carbon, including poor heavy metal removal ability in acidic media and secondary pollution risks resulting from disposable use. The research findings can offer a novel technical reference and feasible approach for the purification of acidic rare earth wastewater in practical engineering applications. Full article

The stable crosslinked structure of glass-fiber-reinforced epoxy composites in end-of-life wind turbine blades complicates their recycling and reuse. Mechanically ground blade powder can be incorporated into new epoxy systems, but its heterogeneous surface composition and limited compatibility with the matrix restrict its reinforcing efficiency. In this study, sequential NaOH activation and KH560 treatment were used to regulate the surface characteristics of recycled wind-turbine-blade powder. FTIR and direct powder XPS measurements revealed changes in the hydroxylated silicate environment and the introduction of KH560-associated organic and organosilicon surface species. Representative SEM observations showed greater resin attachment and a more integrated local powder-matrix morphology after sequential treatment. At a fixed recycled-powder loading of 40 phr, corresponding to approximately 28.4 wt% of the total uncured mixture, EP-KH560 achieved mean flexural and tensile strengths of 67.00 and 38.81 MPa, respectively. These values were 47.8% and 57.1% higher than those of the composite containing untreated powder. Under the fixed formulation and processing conditions investigated, the results demonstrate that sequential NaOH/KH560 treatment improves the interfacial compatibility and comparative mechanical performance of recycled wind-turbine-blade powder/epoxy composites. Full article

In this study, bacitracin—a small-molecule antibacterial agent—was incorporated into the network structure of a type I collagen/bacterial cellulose (Col/BC) composite via in situ recombination and impregnation adsorption, leveraging the well-established drug-loading capacity and sustained-release characteristics of type I collagen. The obtained BA@Col/BC (BA@CBC) functional dressing features a well-defined nanoporous architecture, high porosity (83.9 ± 1.8%), rapid water absorption kinetics, substantial water absorption capacity (48.7 ± 2.4 g/g), and satisfactory moisture permeability (2984 ± 56 g·m²·day). Critically, the introduction of type I collagen not only effectively delays the release of bacitracin, but also significantly improves the cytocompatibility of the bacterial cellulose-based dressing. BA@CBC exhibits powerful antibacterial activities against S. aureus and MRSA, and can promote the proliferation of NIH3T3 and HUVEC, demonstrating excellent cytocompatibility. In vivo studies in a murine infected-wound model revealed that BA@CBC significantly accelerates wound closure compared to controls; histological evaluation further showed the most organized re-epithelialization, robust granulation tissue formation, and de novo hair follicle regeneration in the BA@CBC group. Fluorescence immunohistochemical analysis confirmed markedly reduced expression of pro-inflammatory cytokines IL-1β and TNF-α in BA@CBC-treated wounds, indicating effective suppression of excessive inflammation and consequent improvement of the wound microenvironment. Collectively, BA@CBC integrates favorable physicochemical properties, sustained antibacterial functionality, and superior cytocompatibility—positioning it as a promising candidate for clinical management of infected wounds. Full article

Introduction: Diabetic retinopathy (DR) is characterized by early retinal neurodegeneration accompanied by progressive alterations of the retinal microvasculature, both exacerbated by hyperglycemia-induced oxidative stress and inflammation. Mitochondrial dysfunction critically contributes to neuronal loss and vascular impairment. The 18 kDa Translocator Protein (TSPO) is a mitochondrial outer membrane protein whose expression is increased in activated retinal glial cells and represents a promising target to modulate neuroinflammation and oxidative stress. This study evaluates the therapeutic potential of the TSPO ligand PIGA-1138 in experimental models of DR. Methods: PIGA-1138 (3 µM in vitro; 10 mg/kg/day, i.p., in vivo) was evaluated in high glucose (HG)-exposed 661W retinal cells and in streptozotocin (STZ, 150 mg/kg)-induced diabetic C57BL/6J mice. Cell viability, mitochondrial function, oxidative stress, and Nrf2, HO-1, and SOD1 expression were assessed in vitro. Retinal function and morphology were evaluated in vivo by electroretinography (ERG), visual acuity testing, and optical coherence tomography (OCT) at 30 and 60 days after diabetes induction. Results: PIGA-1138 significantly improved cell viability, reducing apoptosis (TUNEL p ≤ 0.01), preserving mitochondrial membrane potential (MitoRed p ≤ 0.01), reducing oxidative damage, and enhancing Nrf2 nuclear translocation together with HO-1 (p ≤ 0.05) and SOD1 (p ≤ 0.01) expression in HG-treated retinal cells. In diabetic mice, treatment preserved ERG responses and limited retinal thinning at 60 days (p ≤ 0.01), while showing a trend toward preserving visual acuity. Conclusions: Targeting mitochondrial TSPO with PIGA-1138 attenuates key hallmarks of DR by mitigating oxidative stress, suppressing neuroinflammation, and preserving retinal structure and function. These findings support TSPO as a potential disease-modifying target for DR. Full article

Biochar has attracted increasing attention as a low-cost catalyst for biomass pyrolysis due to its developed pore structure, abundant surface functional groups and tunable physicochemical properties. In this study, biochars loaded with alkali and alkaline earth metal (AAEM) species were prepared by pyrolyzing cellulose impregnated with different chloride and acetate salts, including NaCl, KCl, CaCl₂, MgCl₂, CH₃COONa, CH₃COOK, (CH₃COO)₂Ca and (CH₃COO)₂Mg. The resulting AAEM-loaded biochars were subsequently employed as catalysts for cellulose pyrolysis to investigate their effects on product distribution, particularly levoglucosan (LG) and levoglucosenone (LGO) formation. SEM and XRD analyses revealed that the AAEM precursor significantly affected the morphology and phase composition of the biochars. Chloride-derived biochars retained crystalline salt phases or formed corresponding metal oxides, whereas acetate-derived biochars exhibited more dispersed metal-containing species. The introduction of AAEM-loaded biochars generally decreased bio-oil and LG yields while increasing char production, indicating enhanced secondary cracking and repolymerization reactions. Among the investigated catalysts, alkali metal-loaded biochars exhibited stronger inhibition toward LG formation than alkaline earth metal-loaded biochars. The catalytic effects followed the order of C-KCl ≈ C-NaCl > C-MgCl₂ > C-CaCl₂ for chloride-derived biochars and C-CH₃COOK ≈ C-CH₃COONa > C-(CH₃COO)₂Mg > C-(CH₃COO)₂Ca for acetate-derived biochars. Notably, C-(CH₃COO)₂Ca and C-(CH₃COO)₂Mg slightly promoted LGO formation, which was attributed to the synergistic effects of alkaline earth metal species, surface oxygen-containing functional groups and acetate-derived intermediates on dehydration reactions. Thermogravimetric and kinetic analyses further demonstrated that AAEM-loaded biochars reduced the apparent activation energy of cellulose pyrolysis and facilitated thermal decomposition. These findings provide new insights into the catalytic role of AAEM-loaded biochars and suggest a promising strategy for regulating anhydrosugar selectivity, particularly for the production of high-value LGO from biomass pyrolysis. Full article

Introduction: Stroke remains a leading cause of mortality and long-term disability worldwide. Coordinated care delivered through protocol-driven multidisciplinary teams enables rapid diagnosis and treatment, both of which are essential for improving clinical outcomes. Objective: Our objective was to analyze care strategies in the emergency management of acute ischemic stroke, focusing on treatment times and influencing factors, interventions implemented in emergency settings and their impact on clinical outcomes, and the contribution of healthcare professionals to optimizing stroke care. Methods: A systematic review was conducted in accordance with the PRISMA 2020 Statement. Current evidence published between 2021 and 2026 was retrieved from five databases: PubMed, Web of Science, Scopus, Cochrane Library, and SciELO. Eligibility criteria were applied, and methodological quality and risk of bias were assessed using validated appraisal tools. Results: Fourteen studies involving a total of 6384 patients were included. Factors such as healthcare system reorganization, multidisciplinary teamwork, early protocol activation, and the use of stroke-specific triage scales significantly influenced treatment times. Coordinated and protocolized care pathways, together with evidence-based clinical interventions, were consistently associated with higher thrombolysis rates and shorter treatment times, while improvements in neurological and functional recovery were reported in several, but not all, studies. The integration of specialized stroke professionals and structured emergency care processes contributed to reducing treatment delays and improving patient outcomes. Conclusions: Critical treatment times in acute ischemic stroke are influenced by multiple factors, and targeted organizational and clinical strategies can accelerate diagnosis and treatment. Although improvements in clinical outcomes were not consistently demonstrated across all included studies, the available evidence consistently supports protocol-driven multidisciplinary emergency care as an effective strategy for reducing treatment delays and optimizing acute ischemic stroke management. Full article

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts and the persistence of leukemic stem cells (LSCs) within a profoundly remodeled bone marrow (BM) microenvironment. Despite advances in molecular stratification and the introduction of targeted agents, long-term outcomes remain unsatisfactory, particularly in older and high-risk patients. Increasing evidence indicates that leukemogenesis and treatment resistance are critically sustained by a permissive immune milieu, in which LSCs, myeloid-derived suppressor cells, leukemia-associated macrophages, and dysfunctional T and NK cells shape an immunosuppressive “leukemic niche.” This evolving understanding has renewed interest in immune-based strategies capable of restoring effective antitumor immunity. Bispecific antibodies (bsAbs) are engineered molecules designed to engage AML-associated antigens while simultaneously recruiting and activating immune effector cells, most commonly T cells or NK cells. By promoting immune synapse formation independently of major histocompatibility complex expression and conventional co-stimulatory pathways, bsAbs can overcome several mechanisms of immune escape. In this review, we summarize the biological rationale for immunotherapy in AML, with a focus on the role of the BM microenvironment and immune dysregulation. We then discuss the structural and functional properties of IgG-like and non-IgG-like bsAbs, key antigenic targets such as CD33, CD123, CD70 and others, and the main T-cell- and NK-cell-engaging platforms under clinical investigation. Finally, we highlight emerging clinical data, principal toxicities, and the challenges of integrating bsAbs into existing treatment algorithms, including combinations with hypomethylating agents, BCL-2 inhibitors, and allogeneic stem cell transplantation. A deeper understanding of AML immune biology and antigen expression patterns will be essential to optimize bsAb design, maximize therapeutic benefit, and minimize on-target off-tumor toxicity. Full article

Tetrafluoromethane (CF₄) is one of the most stable perfluorinated compounds because of its highly symmetric molecular structure and extremely strong C–F bonds. Catalytic hydrolysis provides a promising route for CF₄ abatement, yet the development of efficient catalysts capable of activating C–F bonds at reduced temperatures remains challenging. Herein, Pt-modified Al₂O₃ catalysts were prepared to promote CF₄ decomposition through the regulation of surface acidity, CF₄ adsorption, and hydroxyl formation. NH₃ temperature-programmed desorption revealed that Pt introduction significantly enhanced the surface acidity of Al₂O₃, while CF₄ temperature-programmed desorption demonstrated strengthened CF₄ adsorption over Pt/Al₂O₃. In situ infrared spectroscopy further showed that Pt incorporation promoted the generation of surface hydroxyl groups under reaction-relevant conditions. These hydroxyl species are proposed to participate in C–F bond activation during CF₄ hydrolysis. As a result, Pt/Al₂O₃ achieved complete CF₄ decomposition at 600 °C and maintained excellent stability during the long-term test, clearly outperforming pristine Al₂O₃. This work demonstrates that Pt/Al₂O₃ is an effective catalyst for CF₄ decomposition by coupling enhanced acidity, improved CF₄ adsorption, and hydroxyl-assisted C–F bond activation. Full article

Continuous monoculture in poplar plantations often leads to declining soil nutrient availability and productivity. Phosphorus (P), in particular, frequently becomes a key limiting factor due to its high fixability and low chemical availability in the soil. Understory vegetation, however, may promote soil P cycling and enhance P availability by regulating the community structure and decomposition activity of soil microorganisms. In this study, a seven-year field experiment was conducted in degraded poplar plantations using a randomized complete block design to investigate the effects of four understory vegetation treatments—understory removal (UR), planting of a nitrogen-fixing species Sesbania cannabina in understory (PN), retention of a single dominant understory species Echinochloa crus-galli (RS), and retention of diverse understory vegetation (RD)—on soil P fractions and availability, and to elucidate the microbial mechanisms driving P cycling using a metagenomic approach. The results showed that, compared with UR, all understory retention treatments significantly increased soil labile P fractions, improved microbial community structure, and enhanced the abundance of P cycling-related functional genes and associated enzyme activities. Specifically, PN enriched the bacterial phylum Chloroflexi, thereby strengthening its role in P cycling, and increased the abundance of key functional genes such as ppa and phnH. These changes led to higher activities of acid phosphatase, phosphodiesterase, and phytase, ultimately improving soil P availability. In contrast, through the input of litter with greater diversity and higher biomass, RD enriched microbial communities dominated by Proteobacteria. This treatment increased the abundance of P cycling-related genes (e.g., phnW, purK, phnP, ugpQ) and associated enzyme activities, thereby enhancing soil P mobilization. Both the introduction of nitrogen-fixing species and the increase in understory species richness promoted soil P cycling and enhanced P availability, albeit through distinct mechanisms. Planting of nitrogen-fixing species enriched specific microbial taxa and functional genes, whereas increasing understory species richness boosts P cycling by increasing bacterial species richness and functional gene abundance. Both enhancing species richness and planting nitrogen-fixing species in the understory effectively improved soil P availability and supported the sustainable management of degraded poplar plantations. Among these approaches, retaining diverse understory vegetation is more cost-effective and contributes to biodiversity conservation, making it a recommended management strategy. Full article