Search Results (2,464)

A key obstacle to the efficacy of cancer drugs is the safe delivery of the drugs to the target site of the disease. Recent advances in nanomedicine have introduced smart hydrogel nanoparticles as promising, efficient, secure, and stimulus-responsive drug carriers. Herein, a bio-safe pH-sensitive nanohydrogel (NG) made of polyaminoethyl methacrylamide (AEMA)-grafted dextran was used as a carrier for liver-targeted doxorubicin (DOX) delivery. Lactobionate (SL) residue was conjugated to the prepared NG as a targeting agent, and DOX was also conjugated via Schiff base linkage. The synthesized structure was analyzed using ¹HNMR, FT-IR, and size exclusion chromatography. DOX release was confirmed through UV-Vis spectroscopy. A pH-responsive manner in the DOX release profile was observed in a simulated medium with pH changes. In vitro toxicity assessment was performed in HepG2 and L929 cell lines, which have demonstrated the biosafety of the prepared hydrogel and its high effectiveness as an anticancer drug delivery system. Full article

This paper provides a systematic review of the latest advancements in metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) for electrocatalytic carbon dioxide reduction. Both materials exhibit high specific surface areas, tunable pore structures, and abundant active sites. MOFs enhance CO₂ conversion efficiency through improved conductivity, optimized stability, and selective regulation—including bimetallic synergy, pulse potential strategies, and tandem catalysis. COFs achieve efficient catalysis through precise design of single or multi-metal active sites, optimization of framework conjugation, and photo/electro-synergistic systems. Both types of materials demonstrate excellent selectivity toward high-value-added products (CO, formic acid, C₂⁺ hydrocarbons), but they still face challenges such as insufficient stability, short operational lifespan, high scaling-up costs, and poor electrolyte compatibility. Future research should integrate in situ characterization with machine learning to deepen mechanistic understanding and advance practical applications. Full article

We present three dimensional particle-in-cell simulations of current-voltage characteristics of the hemispherical Langmuir probe (LAP), onboard the China Seismo-Electromagnetic Satellite (CSES). Using realistic plasma parameters and background magnetic fields obtained from the International Reference Ionosphere (IRI) and International Geomagnetic Reference Field (IGRF) models, we simulate probe–plasma interactions at three locations: the equatorial region and two magnetically conjugate mid-latitude sites: Millstone Hill (Northern Hemisphere) and Rothera (Southern Hemisphere). The simulations, performed using the PTetra PIC code, incorporate realistic LAP geometry and spacecraft motion in the ionospheric plasma. Simulated current voltage characteristics or I–V curves are compared against in-situ LAP measurements from CSES Orbit-026610, with Pearson’s correlation coefficients used to assess agreement. Our findings indicate how plasma temperature, density, and magnetization affect sheath structure and probe floating potential. The study highlights the significance of kinetic modeling in enhancing diagnostic accuracy, particularly in variable sheath regimes where classic analytical models such as the Orbital-Motion-Limited (OML) theory may be inadequate. Full article

Evidence of possible cerebellar involvement in spatial processing, place learning and other types of higher order functions comes mainly from clinical observations, as well as from mutant mice and lesion studies. The latter, in particular, have reported deficits in spatial learning and memory following surgical or neurotoxic cerebellar ablation. However, the low specificity of such manipulations has often made it difficult to precisely dissect the cognitive components of the observed behaviors. Likewise, due to conflicting data coming from lesion studies, it has not been possible so far to conclusively address whether a cerebellar dysfunction is sufficient per se to induce learning deficits, or whether concurrent damage to other regulatory structure(s) is necessary to significantly interfere with cognitive processing. In the present study, the immunotoxin 192 IgG-saporin, selectively targeting cholinergic neurons in the basal forebrain and a subpopulation of cerebellar Purkinje cells, was administered to adult rats bilaterally into the basal forebrain nuclei, the cerebellar cortices or both areas combined. Additional animals underwent injections of the toxin into the lateral ventricles. Starting from two–three weeks post-lesion, the animals were tested on paradigms of motor ability as well as spatial learning and memory and then sacrificed for post-mortem morphological analyses. All lesioned rats showed no signs of ataxia and no motor deficits that could impair their performance in the water maze task. The rats with discrete cerebellar lesions exhibited fairly normal performance and did not differ from controls in any aspect of the task. By contrast, animals with double lesions, as well as those with 192 IgG-saporin given intraventricularly did manifest severe impairments in both reference and working memory. Histo- and immunohistochemical analyses confirmed the effects of the toxin conjugate on target neurons and fairly similar patterns of Purkinje cell loss in the animals with cerebellar lesion only, basal forebrain-cerebellar double lesions and bilateral intraventricular injections of the toxin. No such loss was by contrast seen in the basal forebrain-lesioned animals, whose Purkinje cells were largely spared and exhibited a normal distribution pattern. The results suggest important functional interactions between the ascending regulatory inputs from the cerebellum and those arising in the basal forebrain nuclei that would act together to modulate the complex sensory–motor and cognitive processes required to control whole body movement in space. Full article

Poly(carboxybetaine methacrylate)s (PCBMA) belongs to a class of zwitterionic polymers that offer promising alternatives to polyethylene glycol (PEG) in biomedical applications. This review highlights how the unique zwitterionic structure of PCBMA dictates its strong antifouling behavior, low immunogenicity, and sensitivity to environmental stimuli such as pH and ionic strength. These features make PCBMA promising for designing advanced systems suited for complex biological environments. This review describes PCBMA-based materials—ranging from hydrogels, nanogels, and surface coatings to drug carriers and protein conjugates—and critically evaluates their performance in drug delivery, tissue engineering, diagnostics, and implantable devices. Comparative studies demonstrated that PCBMA consistently outperformed other zwitterionic polymers and PEG in resisting protein adsorption, maintaining bioactivity of conjugated molecules, and ensuring long circulation times in vivo. Molecular dynamics simulations provide additional information into the hydration shells and conformational behaviors of PCBMA in aqueous dispersions. These insights underscore PCBMA’s broad potential as a promising high-performance material for next generation healthcare technologies. Full article

Background/Objectives: Covalent conjugation of an antibiotic vancomycin (VCM) moiety and a photosensitizing mesochlorin (mChl_Pd) unit into one molecular entity may present the potential to produce the combinatorial effect of both antibacterial photodynamic therapeutic (aPDT) and antibiotic activities. Our recent study indicated that a short linkage of <4 (C−C/or C−N) bond distances between these two moieties resulted in significant steric hindrance due to the bulky VCM, which greatly reduces the accessibility of the agent to the cell surface of methicillin-resistant Staphylococcus aureus (MRSA). The observed aPDT efficacy was found to be minimal. Here, we report that the revision of this linkage, via an EG₁₀ unit using identical synthetic procedures, was able to resolve the issue. Methods: Accordingly, the corresponding combinatorial aPDT−antibiotic compound, consisting of two covalently bonded quaternary ammonium pentacationic arms on the mesochlorin chromophore core, designated as VCMe-mChl_Pd-N₁₀⁺ (LC40e⁺), was prepared for applications in antibacterial photodynamic inactivation (aPDI) activity. It was selected to investigate its enhanced binding and targeting ability to the surface of Gram-positive MRSA cells. Subsequent antibacterial photodynamic therapeutic (aPDT) activity to inactivate MRSA was investigated to substantiate the corresponding cell-surface binding effect on the efficacy of aPDT. Results: We found that the covalent combination of 10 positive charges and an MRSA-targeting vancomycin (VCM) moiety in a conjugated structure, functioning as an antibiotic–decacationic photosensitizing agent (Abx-dcPS), was capable of largely improving the MRSA cell-targeting efficiency. Importantly, variation in the chain length of the oligo(ethylene glycol) linker of VCMe-mChl_Pd-N₁₀⁺, which was sufficiently long enough to properly separate the photoactive mesochlorin ring moiety from the VCM moiety within the molecular structure, resulted in significantly enhanced aPDT activity. The new conjugate provided nearly complete eradication (>6.5-log₁₀ colony-forming units (CFU) reduction) of MRSA cells in vitro. The aPDT efficacy followed the order Abx-dcPS (combinatorial decacationic) > dcPS (decacationic) >> nPS (nonionic). This order was also verified by the relative physical binding trend of these PSs using either nPS-, dcPS-, or Abx-dcPS-pretreated and pre-fixed MRSA cells in investigations of fluorescent confocal microscopy, UV–vis fluorescence spectroscopy, and transmission electron microscopy (TEM). Conclusions: Furthermore, the molecular conjugate of Abx-dcPS may provide covalent co-delivery of two drug components concurrently, which might also serve as an effective antibiotic agent after aPDT and potentially prevent the reoccurrence of MRSA-induced infection. Full article

Fractured tight sandstone reservoirs pose challenges for gas development due to low matrix porosity and permeability, complex pore structures, and pervasive fractures. This study focuses on the Bashijiqike Formation in the Keshen Gas Field, Kuqa Depression, aiming to clarify the geological controls on reservoir quality. Lithofacies, diagenetic facies, and fracture facies were systematically classified by core analyses, thin sections, scanning electron microscopy (SEM), cathodoluminescence (CL), X-ray diffraction (XRD), grain size analyses, mercury intrusion capillary pressure (MICP), well logs and resistivity imaging logging (FMI). Their impacts on porosity, permeability and gas productivity were quantitatively assessed. A ternary reservoir quality assessment model was established by coupling these three factors. Results show that five lithofacies, four diagenetic facies, and four fracture facies jointly control reservoir performance. The high-energy gravelly sandstone facies exhibit an average porosity of 6.0% and average permeability of 0.066 mD, while the fine-grained sandstone shows poor properties due to compaction and clay content. Unstable component dissolution facies enhance secondary porosity to 6.0% and permeability to 0.093 mD. Reticulate and conjugate fracture patterns correspond to gas production rates two to five times higher than those with single fractures. These findings support targeted reservoir classification and improved development strategies for ultra-deep tight gas reservoirs. Full article

This study introduces the Gyroid structure, a type of triply periodic minimal surface (TPMS), for enhanced effusion cooling performance. Conjugate heat transfer simulations are used to compare the flow behavior, pressure loss, and overall cooling effectiveness of single- and double-wall Gyroid configurations against a baseline film hole model at blowing ratios of 0.5–2.0. Results show that the Gyroid design eliminates jet lift-off and counter-rotating vortex pairs, ensuring full coolant coverage and a thicker coolant layer than the baseline. The double-wall configuration further improves cooling with jet impingement, yielding higher average Nusselt numbers than the single-wall design. At equal pressure loss, the impingement/Gyroid model outperforms the baseline by 102.7% in cooling effectiveness. To assess manufacturability, a high-resolution CT scan is used to validate a laser powder bed fusion-printed Gyroid sample at gas turbine blade scale, confirming feasibility for industrial application. These findings highlight the superior thermal performance and manufacturability of the 3D-printed Gyroid structure, offering a promising cooling solution for next-generation turbine blades. Full article

Indocyanine green (ICG) is a fluorescent agent which is characterized by a wide range of applications in the proper visualization of the operating field, differentiation of vital structures, and localization of lesions to be excised. An investigation and overview of novel approaches of indocyanine green in modern gynecological oncology was conducted, including ovarian cancer surgery with its compartmental approach and compartmental surgery in endometrial cancer. Ureteral visualization and perfusion, lymphography, lymph node transfers, or the localization of anastomotic leakage in bowel surgery are examples of applications aimed at reducing the risk of surgical complications and improving the patients’ quality of life. The general use of indocyanine green in lymph node detection, subcategorized and analyzed, is constantly improved and reviewed. A therapeutic approach with macromolecules is being tested in preclinical models. Early results could suggest the future application of indocyanine green not only in broad-sense imaging but also as a cytotoxic agent conjugated with macromolecules. Further studies on the application of indocyanine green in laparoscopy, open surgery, and finally as a curative cytotoxic agent are needed. Full article

Since the first paper published by Susan Cole in 1990 detailing multidrug resistance mediated by ABCC1/MRP1, research into the C-subfamily of ATP-binding cassette transporters has continued to uncover a wide range of functionally divergent proteins. However, several orphan transporters remain in the C-subfamily, and the physiological function and substrates of ABCC5, ABCC11, and ABCC12 remain elusive. This review explores the emerging understanding of human ABCC5. Unlike other ABC transporters with well-defined drug export functions, ABCC5’s physiological roles remain only partially understood. While it is known for its involvement in multidrug resistance in cancers, recent studies suggest broader implications in development, metabolism, neurobiology, and male fertility. ABCC5 exports various endogenous substrates, including cyclic nucleotides (cAMP and cGMP), glutamate conjugates like NAAG, and possibly haem. Knockout models in mice, zebrafish, and sea urchins reveal ABCC5’s role in gut formation, brain function, eye development, and iron metabolism. In mice, its deletion results in lower adipose tissue mass, enhanced insulin sensitivity, and neurobehavioral changes resembling schizophrenia, highlighting its role in glutamatergic signalling and circadian regulation. Functionally, ABCC5 appears to impact adipocyte differentiation and GLP-1 release, implicating it in type 2 diabetes susceptibility in humans. Structural studies using human ABCC5 revealed a novel autoinhibitory mechanism involving a peptide segment (C46–S64) that blocks substrate binding, offering new potential for selective inhibitor development. However, this review emphasises caution in targeting ABCC5 for cancer therapy due to its underappreciated physiological function(s), particularly in the brain and male reproductive system. Understanding ABCC5’s substrate specificity, regulatory mechanisms, and functional redundancy with its paralog ABCC12 remains critical for successful therapeutic strategies in humans. Full article

Under the complex geological structural stress of the Western Himalayan syntaxis, the widespread distribution of hard and brittle rocks (such as sandstone and limestone) makes them prone to the formation of conjugate joints, also known as X-joints. These joints create weak structural planes in the slope rock mass, and when combined with weak interlayers within the slope, they result in a complex dynamic response and hazard situation in this region, which is further exacerbated by frequent seismic activity. This poses a serious threat to the planning, construction, and safe operation of the Belt and Road Initiative. To study the slope vibration response and instability mechanisms under these conditions, we conducted a shaking table test using the Iymek avalanche as a case study and performed Hilbert–Huang Transform (HHT) analysis. We also compared the results of the shaking table test on slope models without X-joints but containing weak interlayers. The findings show that the presence of X-joints leads to an earlier onset of plastic failure in the slope. During the failure development, X-joints cause stress concentration and the diversification of stress redistribution paths, delaying energy release. Ultimately, the avalanche failure mode in the X-joint slopes is more dispersed compared to the landslide failure mode in the model without X-joints. At the toe of the slope beneath the weak interlayer, low-frequency seismic waves can cause a significant amplification of acceleration, and the weak interlayer is often the shear outlets of the slope. These findings provide new insights into the seismic failure evolution of jointed slopes with weak interlayers and offer practical references for seismic hazard mitigation in mountainous infrastructure. Full article

Streptococcus pneumoniae has been a PCV10 vaccine-preventable agent in Bulgaria since 2010. Our objective is to determine the phylogenetic structure of 170 invasive and non-invasive pneumococcal isolates, focusing on their serotypes and antimicrobial susceptibility. Serotyping was performed using latex agglutination, capsular swelling reaction, and serotype-specific PCRs. Antibiotic susceptibilities were assessed by broth microdilution. MLST was conducted to define the clonal composition. The non-PCV10 serotypes accounted for 88.2%. The predominant invasive pneumococcal disease (IPD) serotypes were 19A (39.3%), 19F (21.4%), 6C (10.7%), 7F (7.1%), and 3 (7.1%). The prevalent NIPD serotypes were 19A (18.3%), 6C (15.5%), 3 (10.6%), 15A (7.7%), and 6A (6.3%). The overall antimicrobial non-susceptibility rates were: benzylpenicillin (55.2%), ceftriaxone (15.2%), cefuroxime (35.8%), amoxicillin-clavulanic acid (38.8%), erythromycin (60.5%), clindamycin (57.0%), tetracycline (43.5%), trimethoprim-sulfamethoxazole (62.9%), and chloramphenicol (13.5%). The multidrug resistance (MDR) strains were 60.5%. The predominant clone CC320, represented 20.0% MDR 19A and 19F strains linked to Taiwan^19F-14 and GPSC1. CC273/Greece^6B-22 and CC386 accounted for 5.3% 6A and 6C isolates. Most serotype 3 isolates are associated with CC505, associated with Netherlands³-31 and GPSC12. Switching to a conjugate vaccine with broader serotype coverage could reduce the incidence of 19A, 6C, and 15A MDR S. pneumoniae clones in our country. Full article

Due to its conjugated structure, 1,4,6,8-tetrakis((E)-2-(thiophen-2-yl)vinyl)azulene (L) has a high potential for nonlinear optics and coloring. This compound was studied electrochemically using cyclic voltammetry, pulse differential voltammetry and rotating disk voltammetry in organic electrolytes. The main processes occurring during oxidation and reduction scans were highlighted and characterized. Density functional theory (DFT) calculations were conducted to assess the chemical reactivity of this compound. UV-Vis studies of L were performed in acetonitrile to establish the optical parameters in this solvent and its complexing power towards heavy metal (HM) ions. Chemically modified electrodes (CMEs) based on L were prepared by electrooxidation of L in organic electrolytes. To evaluate the electrochemical behavior of the CMEs, they were characterized with a ferrocene redox probe. They were also tested for the analysis of synthetic samples of heavy metal ions (HM): Cd(II), Pb(II), Cu(II) and Hg(II) by anodic stripping. Specific responses were obtained for Pb(II) and Cd(II) ions. The preparation conditions have an influence on the electrochemical responses. This study is relevant for the design and further development of advanced materials based on this azulene for the analysis of HMs in water samples. Electrochemical experiments and DFT calculations recommended L as a new ligand for modifying the electrode surface for the analysis of HMs. Full article

1,3-Butadiene and its analogues constitute an important raw material in the petrochemical industry. What is more, due to their specific structure, these compounds are attractive components in the synthesis of heterocyclic compounds. Modification of the 1,3-butadiene structure allows obtaining compounds characterized by different reactivity and possessing various biological properties. In order to thoroughly investigate this phenomenon, an analysis of 20 compounds, including 1,3-butadiene and its analogues, was carried out. For this purpose, a study based on MEDT, ADME, and PASS was performed. In this research, changes in electronic properties and basic physicochemical parameters under the presence of various substituents at various positions in the structure of 1,3-butadiene were studied. At the end, the influence of modifications on biological activities for the tested compounds was evaluated. Based on the presented results, it was found that substituent modifications cause significant changes in both electronic structures and in physicochemical properties of all the compounds. This fact is probably caused by the small size of the considered compounds. On the other hand, the main preferences for the most important active sites in the tested molecules remain the same due to the presence of a strongly conjugated system of double bonds. Full article

Fatty acid binding proteins FABP3 and FABP4 act as intracellular lipid chaperones that influence fatty acid transport and metabolism in mammary tissue, and genetic variation in these genes may affect milk composition. We examined the associations between FABP3 and FABP4 polymorphisms and milk composition and fatty acid profiles in 200 lactating Native Southern Yellow (NSY) cows. DNA from each cow was PCR-amplified and Sanger-sequenced for FABP3 and FABP4; genotypes were tested for their association with milk fatty acid concentrations and standard composition traits using linear models adjusted for relevant covariates. We detected a missense variant in FABP3 (c.3656G > A; p.Val45Met) and an intronic SNP in FABP4 (g.3509T > C). The FABP3 p.Val45Met AA genotype was associated with higher concentrations of butyric, palmitic, oleic, and α-linolenic acids. Cows with the FABP4 TC genotype exhibited elevated levels of myristoleic, γ-linolenic, conjugated linoleic, and arachidic acids, along with increased fat-free dry matter, protein, and lactose. In silico analyses provided mixed evidence for the structural effects of p.Val45Met, molecular docking suggested altered ligand affinity for several fatty acids, and splice site prediction implicated g.3509T > C in possible transcript processing changes. These variants constitute candidate markers for milk fatty acid composition in NSY cattle; replication in independent cohorts and functional validation are recommended to confirm their utility for milk quality improvement. Full article