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RSC Advances Jun 2024Photodynamic therapy (PDT) is an alternative, minimally invasive treatment for human diseases such as cancer. PDT uses a photosensitizer to transfer photon energy...
Photodynamic therapy (PDT) is an alternative, minimally invasive treatment for human diseases such as cancer. PDT uses a photosensitizer to transfer photon energy directly to cellular O to generate O (Type II), the toxicity of which leads to cancer cell death. In this work, the photoluminescence mechanisms of a BF-formazanate dye sensitizer (BF-FORM) and its iodinated derivative (BF-FORM-D) were studied using complementary theoretical approaches; the photoluminescence pathways in the S and T states were studied using density functional theory (DFT) and time-dependent (TD)-DFT methods, the kinetic and thermodynamic properties of the pathways using the transition state theory (TST), and the time evolution and dynamics of key processes using non-adiabatic microcanonical molecular dynamics simulations with surface-hopping dynamics (NVE-MDSH). Evaluation of the potential energy surfaces (PESs) in terms of the rotations of the phenyl rings suggested a pathway for the S → S transition for the perpendicular structure, whereas two pathways were anticipated for the T → S transition, namely, [T → S] occurring immediately after the S/T intersystem crossing (ISC) and [T → S] occurring after the S/T ISC and T equilibrium structure relaxation, with the T → S energy gap being comparable to the energy required for O → O. The PESs also showed that because of the heavy-atom effect, BF-FORM-D possessed a significantly smaller S/T energy gap than BF-FORM. The TST results revealed that at room temperature, BF-FORM-D was thermodynamically more favorable than the parent molecule. Analysis of the NVE-MDSH results suggested that the librational motions of the phenyl rings play an important role in the internal conversion (IC) and ISC, and the S/T ISC and T → S transitions could be enhanced by varying the irradiation wavelength and controlling the temperature. These findings can be used as guidelines to improve and/or design photosensitizers for PDT.
PubMed: 38915335
DOI: 10.1039/d4ra02240h -
RSC Advances Jun 2024A process employing extrusion was used to produce multicore microcapsules composed of multiple beads. The inner beads were made from κ-carrageenan (κ-c), a...
A process employing extrusion was used to produce multicore microcapsules composed of multiple beads. The inner beads were made from κ-carrageenan (κ-c), a thermo-responsive linear sulphated polymer whose gelling temperature ranges at 40-60 °C, depending on the concentration of κ-c polymer and the amount of potassium chloride used for gelation. The resulting beads were then enveloped by chitosan through gelation with sodium triphosphate. The pesticide ammonium glufosinate was encapsulated in the κ-c/chitosan multicore microcapsules for demonstration of controlled release of the encapsulant. It was found that in response to an external stimulus, such as elevated temperature or solar simulation, the microcapsules exhibit the gradual release of encapsulated pesticide molecules from multicore microcapsules, compared with beads only. This process of making multicore microcapsules can be extended to other polymer pairs based on applications. This work is relevant to agriculture, where the controlled-release of the pesticides or fertilizers could be triggered by the sun and/or temperature changes, thus extending the residual period of the chemicals as well as decreasing the extent of pollution by leaching of abundant chemicals.
PubMed: 38915334
DOI: 10.1039/d4ra03131h -
RSC Advances Jun 2024Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently...
Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently needed to develop new antibacterial drugs with unique mechanisms of action. As a versatile moiety, morpholine has been widely employed to enhance the potency of numerous bioactive molecules. In this study, a series of ruthenium-based antibacterial agents modified with the morpholine moiety were designed and characterized, aiming to obtain a promising metalloantibiotic with a multitarget mechanism. Antibacterial activity screening demonstrated that the most active complex Ru(ii)-3 exhibited the strongest potency against () with an MIC value of only 0.78 μg mL, which is better than most clinically used antibiotics. Notably, Ru(ii)-3 not only possessed excellent bactericidal efficacy, but could also overcome bacterial resistance. Importantly, Ru(ii)-3 very efficiently removed biofilms produced by bacteria, inhibited the secretion of bacterial exotoxins, and enhanced the activity of many existing antibiotics. The results of mechanism studies confirmed that Ru(ii)-3 could destroy the bacterial membrane and induce ROS production in bacteria. Furthermore, animal infection models confirmed that Ru(ii)-3 showed significant anti-infective activity . Overall, this work demonstrated that a morpholine-modified ruthenium-based agent is a promising antibiotic candidate in tackling the crisis of drug-resistant bacteria.
PubMed: 38915333
DOI: 10.1039/d4ra02667e -
RSC Advances Jun 2024In this work, we describe a facile method for generating monodisperse Au@Ag core-shell nanocubes with well-controlled size and fine-tuned Ag shell thicknesses. In this...
In this work, we describe a facile method for generating monodisperse Au@Ag core-shell nanocubes with well-controlled size and fine-tuned Ag shell thicknesses. In this synthesis method, Au nanocubes were prepared the seed-mediated growth method. Then, Au@Ag nanocubes with the core-shell structure were prepared separately by reducing AgNO with AA using as-prepared Au nanocubes as seeds. The thickness of Ag shells could be finely tuned from 3.6 nm to 10.0 nm by varying the concentration of the AgNO precursor. By investigating the localized surface plasmon resonance (LSPR) properties of Au@Ag nanocubes in relation to the thickness of the Ag shell, we found that the intensity of the characteristic peak of Ag gradually increases and that of Au gradually decreases as the thickness of the Ag shell increases. Additionally, surface-enhanced Raman scattering (SERS) properties of Au@Ag core-shell nanocubes were evaluated using rhodamine 6G (R6G) as the probe molecule. Interestingly, Au@Ag nanocubes exhibit efficient SERS intensities compared to the Au nanocubes, and Ag shell with a thickness of about 8.4 nm exhibits the optimal SERS activity. In addition, our results also demonstrated that Au@Ag nanocubes with an Ag shell thickness of 8.4 nm exhibited high SERS sensitivity and are capable of probing the analyte down to 10 M. The results obtained here suggest that Au@Ag core-shell nanocubes might serve as a nanoprobe for SERS-based analytical and biosensing applications.
PubMed: 38915331
DOI: 10.1039/d4ra03135k -
Clinical Chemistry and Laboratory... Jun 2024Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to...
OBJECTIVES
Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation.
METHODS
A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries. Participants provided insights into their experience levels, knowledge, and usage of metabolomics approaches, along with detailing the applications and methodologies employed.
RESULTS
Findings revealed a varying level of experience among respondents, with varying degrees of familiarity and utilization of metabolomics techniques. Targeted approaches dominated the field, particularly liquid chromatography coupled to a triple quadrupole mass spectrometer, with untargeted methods also receiving significant usage. Applications spanned clinical research, epidemiological studies, clinical diagnostics, patient monitoring, and prognostics across various medical domains, including metabolic diseases, endocrinology, oncology, cardiometabolic risk, neurodegeneration and clinical toxicology.
CONCLUSIONS
Despite optimism for the future of clinical metabolomics, challenges such as technical complexity, standardization issues, and financial constraints remain significant hurdles. The study underscores the promising yet intricate landscape of metabolomics in clinical practice, emphasizing the need for continued efforts to overcome barriers and realize its full potential in patient care and precision medicine.
PubMed: 38915248
DOI: 10.1515/cclm-2024-0550 -
Clinical and Molecular Hepatology Jun 2024Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for...
BACKGROUND/AIMS
Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
METHODS
Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth.
RESULTS
Based on 1423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy.
CONCLUSIONS
UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.
PubMed: 38915206
DOI: 10.3350/cmh.2024.0236 -
Scientific Reports Jun 2024Investigating surfactant effects on the floatability of Wiser bituminous coal holds significant importance in improving coal cleanliness and utilization value. Using...
Investigating surfactant effects on the floatability of Wiser bituminous coal holds significant importance in improving coal cleanliness and utilization value. Using density functional theory and molecular dynamics simulation methods, this study constructed models of Wiser bituminous coal and examined the impact of different surfactants, including the anionic surfactant sodium dodecyl benzene sulfonate, the cationic surfactant hexadecyl trimethyl ammonium bromide (CTAB), and the non-ionic surfactant fatty alcohol ethoxylated ether. The focus was on investigating the charge distribution characteristics of these molecules and the modifying effect of binary surfactants on the hydrophobicity of bituminous coal. Results revealed that the maximum electrostatic potential was concentrated near oxygen/nitrogen/sulfur-containing functional groups like sulfonic acid groups, quaternary ammonium cations, ethylene oxide, hydroxyl groups, carboxyl groups, and sulfur bonds. These functional groups exhibited a propensity for accepting/delivering electrons to form hydrogen bonds. Among the surfactants tested, CTAB revealed the slightest difference in frontier orbital energy, measuring 3.187 eV, thereby demonstrating a superior trapping ability compared with the other two surfactants. Adsorption reactions within the system were determined to be spontaneous, with over 60% of the interaction force attributed to electrostatic forces. Moreover, the repulsive force magnitude with water molecules followed the trend: sulfonate group (2.20 Å) < ethylene oxide (2.43 Å) < quaternary ammonium cation (2.57 Å), indicating more excellent water repellency of CTAB. Findings showed that CTAE binary surfactants proved most effective in modifying the hydrophobicity of bituminous coal. This study offers valuable insights into reducing waste, pollution, and resource wastage.
PubMed: 38914729
DOI: 10.1038/s41598-024-65466-7 -
Communications Biology Jun 2024Transporters are targeted by endogenous metabolites and exogenous molecules to reach cellular destinations, but it is generally not understood how different substrate...
Transporters are targeted by endogenous metabolites and exogenous molecules to reach cellular destinations, but it is generally not understood how different substrate classes exploit the same transporter's mechanism. Any disclosure of plasticity in transporter mechanism when treated with different substrates becomes critical for developing general selectivity principles in membrane transport catalysis. Using extensive molecular dynamics simulations with an enhanced sampling approach, we select the Arabidopsis sugar transporter AtSWEET13 as a model system to identify the basis for glucose versus sucrose molecular recognition and transport. Here we find that AtSWEET13 chemical selectivity originates from a conserved substrate facial selectivity demonstrated when committing alternate access, despite mono-/di-saccharides experiencing differing degrees of conformational and positional freedom throughout other stages of transport. However, substrate interactions with structural hallmarks associated with known functional annotations can help reinforce selective preferences in molecular transport.
Topics: Arabidopsis; Arabidopsis Proteins; Substrate Specificity; Molecular Dynamics Simulation; Glucose; Sucrose; Membrane Transport Proteins; Biological Transport; Sugars
PubMed: 38914639
DOI: 10.1038/s42003-024-06291-6 -
Scientific Reports Jun 2024Hydrogen peroxide is considered deleterious molecule that cause cellular damage integrity and function. Its key redox signaling molecule in oxidative stress and exerts...
Hydrogen peroxide is considered deleterious molecule that cause cellular damage integrity and function. Its key redox signaling molecule in oxidative stress and exerts toxicity on a wide range of organisms. Thus, to understand whether oxidative stress alters visual development, zebrafish embryos were exposed to HO at concentration of 0.02 to 62.5 mM for 7 days. Eye to body length ratio (EBR) and apoptosis in retina at 48 hpf, and optomotor response (OMR) at 7 dpf were all measured. To investigate whether hydrogen peroxide-induced effects were mediated by oxidative stress, embryos were co-incubated with the antioxidant, glutathione (GSH) at 50 μM. Results revealed that concentrations of HO at or above 0.1 mM induced developmental toxicity, leading to increased mortality and hatching delay. Furthermore, exposure to 0.1 mM HO decreased EBR at 48 hpf and impaired OMR visual behavior at 7 dpf. Additionally, exposure increased the area of apoptotic cells in the retina at 48 hpf. The addition of GSH reversed the effects of HO, suggesting the involvement of oxidative stress. HO decreased the expression of eye development-related genes, pax6α and pax6β. The expression of apoptosis-related genes, tp53, casp3 and bax, significantly increased, while bcl2α expression decreased. Antioxidant-related genes sod1, cat and gpx1a showed decreased expression. Expression levels of estrogen receptors (ERs) (esr1, esr2α, and esr2β) and ovarian and brain aromatase genes (cyp19a1a and cyp19a1b, respectively) were also significantly reduced. Interestingly, co-incubation of GSH effectivity reversed the impact of HO on most parameters. Overall, these results demonstrate that HO induces adverse effects on visual development via oxidative stress, which leads to alter apoptosis, diminished antioxidant defenses and reduced estrogen production.
Topics: Animals; Oxidative Stress; Apoptosis; Zebrafish; Hydrogen Peroxide; Antioxidants; Zebrafish Proteins; Glutathione; Retina; Estrogens; Gene Expression Regulation, Developmental; Embryo, Nonmammalian; Vision, Ocular
PubMed: 38914633
DOI: 10.1038/s41598-024-64933-5 -
Scientific Reports Jun 2024Circulating leukocytes enter tissue either through endothelial junctions (paracellular) or via a pore through the body of endothelial cells (transcellular). We have...
Circulating leukocytes enter tissue either through endothelial junctions (paracellular) or via a pore through the body of endothelial cells (transcellular). We have previously shown that genetically replacing VE-cadherin with a VE-cadherin-α-catenin (VEC-αC) fusion construct-which binds constitutively to actin-obstructs junctions, and blocks leukocyte extravasation in lung, skin and postcapillary venules of cremaster muscle. However, neutrophil recruitment into the inflamed peritoneal cavity was unimpaired. Investigating reasons for this, here, we visualized neutrophil diapedesis by 3D intravital video microscopy in the cremaster muscle and omentum, the major site of neutrophil recruitment into the peritoneal cavity. We found that 80% of neutrophil-extravasation occurred through HEVs in the omentum, which was unimpaired by VEC-αC. In addition, in larger venules (60-85 µm) of both tissues, less than 15% of neutrophils extravasated transcellularly in WT mice. However, in VEC-α-C mice, transcellular diapedesis increased severalfold in the omentum, but not in the cremaster. In line with this, omental venules expressed higher levels of ICAM-1 and atypical chemokine receptor 1. Furthermore, only in the omentum, VEC-αC expression caused reduced elongation of venular endothelium in flow-direction, suggesting different biomechanical properties. Collectively, VEC-αC does not inhibit paracellular transmigration in all types of venules and can modulate the diapedesis route.
Topics: Animals; Neutrophils; Mice; Transendothelial and Transepithelial Migration; Omentum; Cadherins; Venules; Intercellular Adhesion Molecule-1; Endothelial Cells; Antigens, CD; Neutrophil Infiltration; Mice, Inbred C57BL; Transcellular Cell Migration
PubMed: 38914623
DOI: 10.1038/s41598-024-65173-3