Search Results (13,367)

In this study, a strain of green microalga adapted to the extreme environmental conditions of the Tibetan Plateau was isolated from the Lalu Wetland. The isolate was identified and tentatively designated as Micractinium sp. LL-1. Following the inoculation of strain LL-1 into tannery wastewater, the ammonia nitrogen concentration was rapidly reduced, achieving a removal efficiency of 98.7%. The maximum accumulated biomass reached 1641.68 mg/L and 1461.28 mg/L. Integrated transcriptomic and label-free quantitative proteomic approaches were employed to systematically investigate the molecular response mechanisms of LL-1 under tannery wastewater stress. Transcriptomic analysis revealed that differentially expressed genes were enriched in pathways related to cell proliferation, morphogenesis, intracellular transport, protein synthesis, photosynthesis, and redox processes. Proteomic analysis indicated that LL-1 enhances cellular and enzymatic activities, strengthens regulatory capacity, modulates key metabolic pathways, and upregulates stress-responsive proteins. Under tannery wastewater stress, LL-1 exhibits dynamic adaptation involving signal perception and metabolic reconfiguration through the coordinated regulation of multiple pathways. Specifically, ribosomal translation and nucleic acid binding regulate biosynthetic capacity; the redistribution of energy metabolism boosts photosynthetic carbon fixation and ATP generation; and membrane transport coupled with antioxidant mechanisms mitigates stress-induced damage. Collectively, this study provides theoretical insights into microalgal adaptation to complex wastewater environments and offers potential targets for strain improvement and wastewater valorization. Full article

Introduction: Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health concern due to the limited effectiveness of current treatments, especially in the chronic stage. Objective: Here, we wanted to advance a library of 30 N,N′-disubstituted diamines as promising antichagasic agents and gain insight into the mechanism of action. Methods: The library was evaluated for activity against the T. cruzi amastigote stage and trypanocidal efficacy. In addition, selected compounds were tested as potential polyamine transport inhibitors, and a fluorescent analog was employed to investigate compound internalization. Results: Five compounds exhibited potent activity (pIC₅₀ > 6.0), particularly those with short aliphatic linkers (3–6 carbon atoms), suggesting a structure–activity relationship favouring shorter chains. Mechanistic studies showed that compound 3c strongly inhibited polyamine transport, a vital pathway in T. cruzi, though this was not a universal mechanism among active hits, indicating the potential for multiple targets. A fluorescent analog confirmed intracellular uptake in amastigotes but lacked antiparasitic activity, likely due to disrupted pharmacophoric features. Importantly, none of the compounds demonstrated trypanocidal activity in long-term assays, and some showed cytotoxicity, particularly in the benzyloxy-substituted series. Conclusions: These findings position N,N′-disubstituted diamines as a viable scaffold for Chagas disease drug discovery. However, further optimization is required to enhance selectivity, achieve trypanocidal effects, and better understand the underlying mechanisms of action. Full article

Since the number of existing steel-reinforced concrete buildings affected by carbonation-induced corrosion is steadily increasing, there is a high demand for durable repair methods. Chemical re-alkalization (CRA) represents one such approach, relying on the transport of alkaline pore solution from a repair mortar into carbonated concrete. With the introduction of clinker-reduced binder systems such as hybrid alkali-activated binders (HAABs), their suitability for CRA and governing material parameters require further clarification. In this study, material-related chemical and structural influences on CRA were investigated using an adapted form of Fick’s second law of diffusion, incorporating a time-dependent attenuation factor, β(t). The CRA progression was evaluated over 28 days, distinguishing between an initial suction phase and a subsequent diffusion phase. The results show that a high initial alkalinity of the mortar pore solution (pH > 14) significantly enhances re-alkalization during the suction phase, reflected by suction factors a > 1. In contrast, progression during the diffusion phase is primarily governed by the potassium concentration gradient at the mortar–concrete interface, while structural parameters such as capillary porosity show no systematic correlation with the deceleration factor b (−0.46 ≤ b ≤ −0.26). The findings indicate that, within the investigated range, mortar pore solution chemistry has a stronger influence on CRA than structural properties, providing guidance for the targeted design of alkaline repair mortars. Full article

Canagliflozin (CFZ), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is extensively utilized in the management of type 2 diabetes. Among its various polymorphic forms, the hemi-hydrate (Hemi-CFZ) has been selected as the active pharmaceutical ingredient (API) for CFZ tablets due to its superior solubility. However, during the production, storage, and transportation of CFZ tablets, Hemi-CFZ can undergo transformations into anhydrous (An-CFZ) and monohydrate (Mono-CFZ) forms under the influence of environmental factors such as temperature, humidity, and pressure, which may adversely impact the bioavailability and clinical efficacy of CFZ tablets. Therefore, it is imperative to develop rapid, accurate, non-destructive, and non-contact methods for quantifying An-CFZ and Mono-CFZ content in CFZ tablets to control polymorphic impurity levels and ensure product quality. This research evaluated the feasibility and reliability of using near-infrared spectroscopy (NIR) combined with partial least squares regression (PLSR) for simultaneous quantitative analysis of An-CFZ and Mono-CFZ in CFZ tablets, elucidating the quantifying mechanisms of the quantitative analysis model. Orthogonal experiments were designed to investigate the effects of different pretreatment methods and ant colony optimization (ACO) algorithms on the performance of quantitative models. An optimal PLSR model for simultaneous quantification of An-CFZ and Mono-CFZ in CFZ tablets was established and validated over a concentration range of 0.0000 to 10.0000 w/w%. The resulting model, Y_{An-CFZ/Mono-CFZ} = 0.0207 + 0.9919 X, achieved an R² value of 0.9919. By analyzing the relationship between the NIR spectral signals selected by the ACO algorithm and the molecular structure information of An-CFZ and Mono-CFZ, we demonstrated the feasibility and reliability of the NIR-PLSR approach for quantifying these polymorphic forms. Additionally, the mechanism of PLSR quantitative analysis was further explained through the variance contribution rates of latent variables (LVs), the correlations between LVs loadings and tablets composition, and the relationships between LV scores and An-CFZ/Mono-CFZ content. This study not only provides a robust method and theoretical foundation for monitoring An-CFZ and Mono-CFZ content in CFZ tablets throughout production, processing, storage, and transportation, but also offers a reliable methodological reference for the simultaneous quantitative analysis and quality control of multiple polymorphic impurities in other similar drugs. Full article

Background: The family Cyprinidae is predominantly restricted to freshwater habitats, making the evolution of diadromy and seawater adaptation exceptionally rare within this group. Pseudaspius hakonensis, a rare anadromous cyprinid, and its strictly freshwater congener P. leptocephalus, provide an ideal comparative model to investigate the molecular mechanisms underlying salinity adaptation. This study aimed to elucidate the tissue-specific transcriptional reprogramming, identify candidate genes and key pathways, and explore their association with seawater acclimation in P. hakonensis. Methods: We performed comparative transcriptomic analyses of gill, liver, and kidney tissues from both species using RNA-Seq. Sequencing reads were aligned to a high-quality reference genome of P. hakonensis. Differential expression analysis was conducted using DESeq2, followed by functional enrichment analyses (GO and KEGG) to identify significant biological processes and pathways. Results: A total of 8784, 5965, and 5719 differentially expressed genes (DEGs) were identified in gill, kidney, and liver tissues, respectively, with the gill showing the highest differences. Functional enrichment revealed tissue-specific roles: gill DEGs were associated with protein synthesis and energy metabolism; kidney DEGs with transport and detoxification; and liver DEGs with metabolic regulation and stress signaling. Cross-tissue analysis highlighted three core pathways consistently enriched: MAPK signaling, ABC transporters, and glutathione metabolism. Key candidate genes, including DUSP10, SLC38A2, ATP8B1, GSTA4, and MGST1, were significantly upregulated in P. hakonensis. Conclusions: This first multi-tissue transcriptomic comparison of an anadromous and a freshwater cyprinid reveals pervasive, tissue-specific molecular reprogramming underlying seawater adaptation in P. hakonensis. The coordinated activation of MAPK signaling, glutathione metabolism, and transporter pathways suggests an integrated regulatory network for osmoregulation and stress resistance. These findings provide novel insights into the genetic basis of salinity adaptation in cyprinids and identify candidate genes for future functional validation. Full article

This study investigates the impact of non-uniform carbon sphere diameter distributions on the structural and electrochemical performance of catalyst layers (CLs) in proton exchange membrane fuel cells (PEMFCs), utilizing the lattice Boltzmann method (LBM) for detailed simulations. The impact of carbon sphere diameter range and gradient distribution on oxygen transport, electrochemical reactivity, and catalyst layer morphology was investigated. The results show that gradient designs of carbon sphere diameters effectively modulate pore size distribution, electrochemically active surface area, and oxygen diffusion pathways within the CL. Specifically, placing larger carbon spheres near the gas diffusion layer improves pore connectivity and oxygen transport, while smaller spheres near the membrane enhance the availability of reaction sites. The three-layered gradient design, particularly the L-M-S configuration, demonstrated superior oxygen distribution, reduced concentration gradients, and increased current density by 15.4%. These findings underline the importance of optimizing carbon sphere diameter distributions for enhancing CL performance. This study offers a novel framework for designing catalyst layers with improved mass transport and electrochemical efficiency, providing significant insights for the future development of high-performance PEMFCs. Full article

Time delays are intrinsic to mitotic regulation, particularly within the spindle assembly checkpoint (SAC) and the spindle position checkpoint (SPOC). These delays emerge from multi-step protein activation, molecular transport, force-dependent conformational transitions, and spatial redistribution of regulatory complexes. They span seconds to minutes and strongly influence checkpoint activation, maintenance, and silencing. Increasing evidence shows that such delayed processes shape mitotic timing, checkpoint robustness, and cell-fate decisions. While classical ordinary differential equation (ODE) models assume instantaneous biochemical responses, delay differential equations (DDEs) provide a natural framework for representing these finite timescales by explicitly incorporating system history. Recent DDE-based studies have revealed how delayed signaling contributes to bistability, oscillatory responses, prolonged mitotic arrest, and variability in checkpoint outputs. This review summarizes the biological origins of delays in SAC and SPOC, including Mad2 activation, MCC assembly and turnover, APC/C reactivation, tension maturation at kinetochores, and Bfa1–Bub2 regulation of Tem1. The article further discusses how mechanistic models with explicit delays improve our understanding of SAC–SPOC ordering, error-correction dynamics, and mitotic exit control. Finally, open challenges and future directions are outlined for integrative delay-aware modeling that unifies biochemical, mechanical, and spatial processes to better explain checkpoint function and chromosomal stability. Full article

The purpose of the study was to characterize the basic structure of nanoparticles (Zein-CS-Cur-Que) embedded in curcumin and quercetin, realize the synergistic antioxidant of dietary polyphenols, and improve the transmembrane transport rate and bioavailability of curcumin. The oral delivery system Zein-CS-Cur-Que developed based on the synergistic encapsulation of curcumin and quercetin using the anti-solvent method with corn alkyd-soluble proteins and sodium caseinate possessed varying nanoparticle sizes (173.96–191.03 nm) and good dispersibility (PDI < 0.17), and relied on electrostatic interactions, hydrogen bonding, and hydrophobic interactions to successfully encapsulate curcumin (94.62%) and quercetin (73.75%). The results showed that Zein-CS-Cur-Que enhanced the stability and antioxidant activity of curcumin, and increased the bioaccessibility (nearly 2-fold) and rate of translocation (nearly 2-fold) of curcumin in the gastrointestinal tract significantly. Therefore, the nanocomposite system developed in this study is crucial for the development of functional foods and dietary supplements, providing effective insights into the synergy of polyphenol interactions. Full article

Implementing effective cycling mobility requires infrastructure that enhances safety and reduces travel time. A common metric for tracking progress is the total length of dedicated cycling infrastructure. However, this does not always correlate with increased cycling usage. For instance, in Italy (2008–2015), cycling infrastructure grew by 48%, but ridership remained unchanged. Design quality and behavioral and contextual factors all influence this dynamic. This study analyzes a 16-year time series (2009–2024) of monthly cyclist flows surveys in Bologna, Italy. It focuses on flows, gender, and bike lane usage. It represents the most detailed and longest series of its kind in the country. The findings show a positive correlation between infrastructure growth (meters per inhabitant) and cyclist flows, though this weakened significantly after COVID-19 and the extensive introduction of non-exclusive bike lanes on mixed-use roads from 2020. Regression analyses reveal that new bike flows per new meter/inhabitant of infrastructure were 3 times greater before 2020. This study identifies two likely causes: the insufficient perceived safety of the newly introduced mixed-traffic lanes from 2020 and the lack of attractivity of cycling for the female population, as highlighted in the decreasing trend in the usage of bike infrastructure by female riders after 2020. Full article

In earthquake-prone regions, improving the seismic performance of bridge abutments is crucial for ensuring the overall safety and resilience of transportation infrastructure. In this study, a novel shallow foundation abutment with anchor plates and steel bundles is proposed. Quasi-static tests incorporating soil–abutment interaction were conducted on a novel shallow foundation abutment and on a conventional abutment to evaluate and compare their seismic performance. The experimental results, including failure mechanism, hysteretic behavior, backbone curve, stiffness, and damping ratio, were analyzed. The findings indicate that the inclusion of anchor plates and steel bundles effectively restricts abutment rotation and significantly enhances its ultimate bearing capacity, with an observed increase of up to 96%. The secant stiffness of the novel shallow foundation abutment is consistently greater than that of a conventional abutment, being on average 20.9% higher before a loading displacement of 20 mm. Moreover, its energy dissipation capacity surpasses that of the common abutment after a loading displacement of 8 mm. Overall, the participation of anchor plates and steel bundles substantially improves the seismic resistance of the soil–abutment interaction system. The conclusions of this study provide valuable guidance for the design, promotion, and practical application of shallow foundation abutments with anchor plates and steel bundles in seismically active areas. Full article

Metalloporphyrin-based covalent organic frameworks (MPor-COFs) are emerging porous crystalline materials that combine the optoelectronic properties of metalloporphyrins with the highly ordered structure of COFs. Such a combination not only extends the light absorption spectrum of COFs by incorporating porphyrins but also improves the separation and transport capabilities of photo-generated electrons and holes by leveraging the structural advantages of organic frameworks. At the same time, the metal ions embedded in the porphyrin ring provide abundant active sites and optimize charge transfer channels, showing particular advantages in photocatalysis. The molecular design, construction, and photocatalytic application of MPor-COFs were reviewed in this paper. The intrinsic relationship among the structure, optoelectronic properties, and specific photocatalytic application received special attention. First, the role of the metal center in regulating the electronic structure and photophysical property of porphyrin monomers was introduced, as well as the impact of bond type on framework stability and charge transport efficiency. Then, the synthesis strategies for MPor-COFs were summarized. Finally, the applications of these materials in photocatalysis were critically reviewed, and their prospects and challenges in energy conversion and environmental remediation were also discussed. Full article

Background: Thymol, a natural phenol with antimicrobial and antioxidant activities, and its derivatives offer promising scaffolds for antimalarial drug development, potentially helping overcome resistance. Materials and Methods: In this study, thymol derivatives were synthesized and assessed as antiplasmodial agents against both resistant and sensitive strains of P. falciparum, as well as Plasmodium knowlesi. The ligand molecules were assessed with Plasmodium falciparum chloroquine resistance transporter (PfCRT)’s potential using in silico molecular docking and ADMET analysis. The parent compound, thymol, was chemically modified through esterification and conjugation with hydroxybenzoic acid and cinnamic acid derivatives to generate analogs with varied substitution patterns. Results: The findings showed that among seven successfully synthesized thymol derivatives, compounds 4 and 6 exhibited notable potency against Plasmodium falciparum 3D7 (EC₅₀ = 6.01 ± 1.7 µM and 6.8 ± 1.1 µM, respectively) with high SI values (16.5 and 14.6, respectively), indicating improved selectivity relative to thymol. The cytotoxicity evaluation against HCF mammalian cells revealed that most thymol derivatives were non-toxic, with CC₅₀ values greater than 99 µM, except for compound 3 (CC₅₀ = 71.4 ± 4.5 µM) and compound 1 (CC₅₀ = 58.4 ± 2.3 µM), which exhibited moderate cytotoxic effects. The molecular docking results showed that compounds 3 (−8.4 kcal/mol), 4 (−8.3 kcal/mol), and 6 (−8.3 kcal/mol) exhibited strong binding affinities toward the PfCRT protein. Conclusions: Therefore, thymol derivative compounds 4 and 6 exhibited stronger antiplasmodial activity in vitro against P. falciparum and P. knowlesi with safety profiles against mammalian cells, targeting PfCRT, highlighting their potential as lead antimalarial candidates. Full article

Metal oxide nanomaterials have emerged as transformative materials in the quest to enhance the energy density and overall performance of lithium-ion batteries (LIBs) and solid-state batteries (SSBs). Their unique properties—including their large surface areas and short ion diffusion pathways—make them ideal for next-generation energy storage technologies. In LIBs, the high surface-to-volume ratio of metal oxide nanomaterials significantly enlarges the active interfacial area and shortens the lithium-ion diffusion paths, leading to an improved high-rate performance and enhanced energy density. Transition metal oxides (TMOs) such as nickel oxide (NiO), copper oxide (CuO), and zinc oxide (ZnO) have demonstrated significant theoretical capacities, while binary systems like NiCuO offer further improvements in cycling stability and energy output. Additionally, layered lithium-based TMOs, particularly those incorporating nickel, cobalt, and manganese, have shown remarkable promise in achieving high specific capacities and long-term stability. The synergistic integration of metal oxides with carbon-based nanostructures, such as carbon nanotubes (CNTs), enhances the electrical conductivity and structural durability further, leading to a superior electrochemical performance in LIBs. In SSBs, the use of oxide-based solid electrolytes like garnet-type Li₇La₃Zr₂O₁₂ (LLZO) and sulfide-based electrolytes has facilitated the development of high-energy-density systems with excellent ionic conductivity and chemical stability. However, challenges such as high interfacial resistance at the electrode–electrolyte interface persist. Strategies like the application of lithium niobate (LiNbO₃) coatings have been employed to enhance interfacial stability and maintain electrochemical integrity. Furthermore, two-dimensional (2D) metal oxide nanomaterials, owing to their high active surface areas and rapid ion transport, have demonstrated considerable potential to boost the performance of SSBs. Despite these advancements, several challenges remain. Morphological optimization of nanomaterials, improved interface engineering to reduce the interfacial resistance, and solutions to address dendrite formation and mechanical degradation are critical to achieving the full potential of these materials. Full article

Nucleated erythroid cells (NECs) have emerged as active participants in immune responses in addition to their canonical oxygen transport function. The subpopulations and immune heterogeneity of chick erythroid cells (ch-ECs) upon infection have not been fully characterized. Single-cell RNA sequencing (scRNA-seq) was used to profile ch-ECs in chicks infected with avian pathogenic Escherichia coli (APEC). Unsupervised clustering uncovered ten distinct ch-EC subpopulations (C1–C10), with significant compositional shifts between infected and control groups. Pseudotime analysis revealed a developmental continuum: C1, C3, C5, and C9 as early progenitors; C2, C4, C6, C7, and C10 as mature erythroid cells; and C8 as a naive population. We revealed 62 immune-related genes, including protein kinases and heat shock proteins, and subpopulation-specific differentially expressed genes (DEGs) linked to immune functions. SCENIC analysis revealed Fos, Srf, and Stat3 as key transcription factors with elevated regulon activity and specificity following infection. Subpopulations C2, C4, C6, and C7, which exhibited marked abundance changes, were scrutinized for immune relevance through integrated multi-omics analysis. Immune-related genes including FOS, AKAP9, HS6ST1, GAB3, TFRC, HSPA8, HSP90AA1, and DNAJB6 were identified. Enrichment analysis indicated activation of the MHC class I antigen presentation pathway, while pathways such as Mitogen-Activated Protein Kinase (MAPK) signaling, NOD-like receptor (NLR) signaling, and the heat shock response were found to be suppressed. In conclusion, this study delineates the immune gene repertoire and signaling networks of ch-ECs during APEC infection, offering new perspectives on NEC immunoregulatory functions. Full article

Metformin, a 60-year-old biguanide and cornerstone of type 2 diabetes therapy, continues to challenge and inspire modern pharmaceutical science. Despite its chemical simplicity, metformin displays highly complex pharmacokinetic and pharmacodynamic behavior driven by transporter dependence, luminal activity, and formulation-sensitive exposure. Originally regarded as limited by low permeability and incomplete absorption, metformin has emerged as a paradigm for gut-targeted therapy, controlled- and delayed-release systems, and personalized pharmaceutics. Growing evidence has repositioned the intestine, rather than systemic plasma exposure, as a major site of action, highlighting the central role of organic cation transporters and multidrug efflux systems in determining efficacy, variability, and gastrointestinal tolerability. Beyond metabolic control, insights into transporter regulation, pharmacogenetics, microbiome interactions, and manufacturing quality have expanded metformin’s relevance as a model compound for contemporary drug development. Advances in formulation design, quality-by-design manufacturing, and regulatory control have further reinforced its clinical robustness, while repurposing efforts in oncology, immunometabolism, and regenerative medicine underscore its translational potential. This review integrates mechanistic pharmacology, formulation science, and clinical translation to position metformin not merely as an antidiabetic agent, but as a didactic model illustrating the evolution of pharmaceutics from molecule-centered design to system-oriented, precision-driven therapy. Full article