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1.
J Robot Surg ; 18(1): 285, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012421

ABSTRACT

OBJECTIVE: To investigate whether the panoramic view offered by robot-assisted laparoscopic pyeloplasty (RALP) reduces the likelihood of missing a crossing vessel compared to open pyeloplasty in cases where initial pyeloplasty fails. METHODS: A single institution redo-pyeloplasty database was reviewed for children treated between January 2012 to July 2023. Clinical history, imaging and operative details were reviewed to identify the etiology for the redo procedure. RESULTS: Cohort consisted of 45 patients undergoing a redo RALP during the study period. 29 of 45 patients had an initial open surgical approach, whereas 16 had an initial RALP. 10 patients were noted to have a missed crossing vessel on redo pyeloplasty - 9 had an initial open approach whereas 1 had an initial RALP (p<0.0001). CONCLUSIONS: RALP may reduce the risk of missing a crossing vessel due to the panoramic view of the surgical field intrinsic to an intraperitoneal RALP approach.


Subject(s)
Kidney Pelvis , Laparoscopy , Robotic Surgical Procedures , Ureteral Obstruction , Humans , Robotic Surgical Procedures/methods , Child , Kidney Pelvis/surgery , Laparoscopy/methods , Female , Male , Ureteral Obstruction/surgery , Child, Preschool , Reoperation/methods , Urologic Surgical Procedures/methods , Adolescent , Infant , Retrospective Studies
2.
Neurooncol Pract ; 11(4): 421-431, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39006522

ABSTRACT

Background: This Danish cohort study aims to (1) compare patterns of care (POC) and survival of patients with multifocal glioblastoma (mGBM) to those with unifocal glioblastoma (uGBM), and (2) explore the association of patient-related factors with treatment assignment and prognosis, respectively, in the subgroup of mGBM patients. Methods: Data on all adults with newly diagnosed, pathology-confirmed GBM between 2015 and 2019 were extracted from the Danish Neuro-Oncology Registry. To compare POC and survival of mGBM to uGBM, we applied multivariable logistic and Cox regression analysis, respectively. To analyze the association of patient-related factors with treatment assignment and prognosis, we established multivariable logistic and Cox regression models, respectively. Results: In this cohort of 1343 patients, 231 had mGBM. Of those, 42% underwent tumor resection and 41% were assigned to long-course chemoradiotherapy. Compared to uGBM, mGBM patients less often underwent a partial (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.6), near-total (OR 0.1, 95% CI 0.07-0.2), and complete resection (OR 0.1, 95% CI 0.07-0.2) versus biopsy. mGBM patients were furthermore less often assigned to long-course chemoradiotherapy (OR 0.6, 95% CI 0.4-0.97). Median overall survival was 7.0 (95% CI 5.7-8.3) months for mGBM patients, and multifocality was an independent poor prognostic factor for survival (hazard ratio 1.3, 95% CI 1.1-1.5). In mGBM patients, initial performance, O[6]-methylguanine-DNA methyltransferase promotor methylation status, and extent of resection were significantly associated with survival. Conclusions: Patients with mGBM were treated with an overall less intensive approach. Multifocality was a poor prognostic factor for survival with a moderate effect. Prognostic factors for patients with mGBM were identified.

3.
Sensors (Basel) ; 24(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38894176

ABSTRACT

We aimed to evaluate the intra-session relative and absolute reliability of obstacle-crossing parameters during overground walking in young adults, and to determine the number of trials required to ensure reliable assessment. We analysed data from 43 young male adults who were instructed to walk at a self-selected velocity on a pathway and to step over an obstacle (height = 15 cm; width = 80 cm, thickness = 2 cm) three times. Spatial-temporal gait parameters of the approaching and crossing phases (i.e., before and after the obstacle) and obstacle clearance parameters (i.e., vertical and horizontal distance between the foot and the obstacle during crossing) were computed using a three-dimensional motion analysis system. Intraclass correlation coefficients were used to compute the relative reliability, while standard error of measurement and minimal detectable change were used to assess the absolute reliability for all possible combinations between trials. Results showed that most spatial-temporal gait parameters and obstacle clearance parameters are reliable using the average of three trials. However, the mean of the second and third trials ensures the best relative and absolute reliabilities of most obstacle-crossing parameters. Further works are needed to generalize these results in more realistic conditions and in other populations.


Subject(s)
Gait , Walking , Humans , Male , Walking/physiology , Young Adult , Gait/physiology , Adult , Reproducibility of Results , Biomechanical Phenomena/physiology
4.
Sensors (Basel) ; 24(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38894458

ABSTRACT

The need to establish safe, accessible, and inclusive pedestrian routes is considered one of the European Union's main priorities. We have developed a method of assessing pedestrian mobility in the surroundings of urban public buildings to evaluate the level of accessibility and inclusion, especially for people with reduced mobility. In the first stage of assessment, artificial intelligence algorithms were used to identify pedestrian crossings and the precise geographical location was determined by deep learning-based object detection with satellite or aerial orthoimagery. In the second stage, Geographic Information System techniques were used to create network models. This approach enabled the verification of the level of accessibility for wheelchair users in the selected study area and the identification of the most suitable route for wheelchair transit between two points of interest. The data obtained were verified using inertial sensors to corroborate the horizontal continuity of the routes. The study findings are of direct benefit to the users of these routes and are also valuable for the entities responsible for ensuring and maintaining the accessibility of pedestrian routes.

5.
Angew Chem Int Ed Engl ; : e202409670, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38943493

ABSTRACT

In thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes (OLEDs), acceleration of reverse intersystem crossing (RISC) and suppression of intersystem crossing (ISC) are demanded to shorten a lifetime of triplet excitons. As a system realizing RISC faster than ISC, inverted singlet-triplet excited states (iST) with a negative energy difference (ΔEST) between the lowest excited singlet and the lowest triplet states have been gathering much attention recently. Here, we have focused on an asymmetric hexa-azaphenalene (A6AP) core to obtain a new insight into iST. Based on A6AP, we have newly designed A6AP-Cz with the calculated ΔEST of -44 meV. The experimental studies of a synthesized A6AP-Cz revealed that the lifetime of delayed fluorescence (τDF) was only 54 ns, which was the shortest among all organic materials. The rate constant of RISC (kRISC = 1.9×107 s-1) was greater than that of ISC (kISC = 1.0×107 s-1). The negative ΔEST of A6AP-Cz was experimentally confirmed from 1) the kRISC and kISC (-45 meV) and 2) the temperature-dependent τDF. 3) The onsets of fluorescence and phosphorescence spectra at 77 K also supported the evidence of negative ΔEST (-73 meV). This study demonstrated the potential of A6AP as an iST core for the first time.

6.
Proc Natl Acad Sci U S A ; 121(25): e2320995121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38865271

ABSTRACT

Meiosis, a reductional cell division, relies on precise initiation, maturation, and resolution of crossovers (COs) during prophase I to ensure the accurate segregation of homologous chromosomes during metaphase I. This process is regulated by the interplay of RING-E3 ligases such as RNF212 and HEI10 in mammals. In this study, we functionally characterized a recently identified RING-E3 ligase, RNF212B. RNF212B colocalizes and interacts with RNF212, forming foci along chromosomes from zygonema onward in a synapsis-dependent and DSB-independent manner. These consolidate into larger foci at maturing COs, colocalizing with HEI10, CNTD1, and MLH1 by late pachynema. Genetically, RNF212B foci formation depends on Rnf212 but not on Msh4, Hei10, and Cntd1, while the unloading of RNF212B at the end of pachynema is dependent on Hei10 and Cntd1. Mice lacking RNF212B, or expressing an inactive RNF212B protein, exhibit modest synapsis defects, a reduction in the localization of pro-CO factors (MSH4, TEX11, RPA, MZIP2) and absence of late CO-intermediates (MLH1). This loss of most COs by diakinesis results in mostly univalent chromosomes. Double mutants for Rnf212b and Rnf212 exhibit an identical phenotype to that of Rnf212b single mutants, while double heterozygous demonstrate a dosage-dependent reduction in CO number, indicating a functional interplay between paralogs. SUMOylome analysis of testes from Rnf212b mutants and pull-down analysis of Sumo- and Ubiquitin-tagged HeLa cells, suggest that RNF212B is an E3-ligase with Ubiquitin activity, serving as a crucial factor for CO maturation. Thus, RNF212 and RNF212B play vital, yet overlapping roles, in ensuring CO homeostasis through their distinct E3 ligase activities.


Subject(s)
Chromosome Pairing , Crossing Over, Genetic , Meiosis , Ubiquitin-Protein Ligases , Animals , Mice , Male , Female , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , Poly-ADP-Ribose Binding Proteins/genetics , Mice, Knockout , Humans , Ligases
7.
Yi Chuan ; 46(6): 502-508, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38886153

ABSTRACT

Ssu72 is a component of the yeast cleavage/polyadenylation factor (CPF) complex, which catalyzes the dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II at S5-P and S7-P. It has been shown that Ssu72 phosphatase is involved in regulating chromosome cohesion during mitosis. To further clarify whether Ssu72 phosphatase affects chromosome separation during meiotic division in Schizosaccharomyces pombe, we utilized green fluorescent protein (GFP) to label centromeres and red fluorescent protein to label microtubule protein Atb2. The entire meiotic chromosome separation process of ssu72∆ cells was observed in real-time under fluorescence microscope. It was found that two spindles of ssu72∆ cells crossed during the metaphase and anaphase of the second meiotic division, and this spindle crossing led to a new type of spore defect distribution pattern. The results of this study can provide important reference significance for studying the roles of phosphatase Ssu72 in higher organisms.


Subject(s)
Meiosis , Schizosaccharomyces pombe Proteins , Schizosaccharomyces , Spindle Apparatus , Schizosaccharomyces/genetics , Schizosaccharomyces/enzymology , Spindle Apparatus/genetics , Spindle Apparatus/metabolism , Schizosaccharomyces pombe Proteins/genetics , Schizosaccharomyces pombe Proteins/metabolism , Chromosome Segregation
8.
Adv Mater ; : e2403584, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38897229

ABSTRACT

Despite multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitters with small full-width at half maximum are attractive for wide color-gamut display and eye-protection lighting applications, their inefficient reverse intersystem crossing (RISC) process and long exciton lifetime induce serious efficiency roll-off, which significantly limits their development. Herein, a novel device concept of building highly efficient tricomponent exciplex with multiple RISC channels is proposed to realize reduced exciton quenching and enhanced upconversion of nonradiative triplet excitons, and subsequently used as a host for high-performance MR-TADF organic light-emitting diodes (OLEDs). Compared with traditional binary exciplex, the tricomponent exciplex exhibits obviously improved photoluminescence quantum yield, emitting dipole orientation and RISC rate constant, and a record-breaking external quantum efficiency (EQE) of 30.4% is achieved for tricomponent exciplex p-PhBCzPh: PO-T2T: DspiroAc-TRZ (50: 20: 30) based OLED. Remarkably, maximum EQEs of 36.2% and 40.3% and ultralow efficiency roll-off with EQEs of 26.1% and 30.0% at 1000 cd m-2 are respectively achieved for its sky-blue and pure-green MR-TADF doped OLEDs. Additionally, the blue emission unit hosted by tricomponent exciplex is combined with an orange-red TADF emission unit to achieve a double-emission-layer blue-hazard-free warm white OLED with an EQEmax of 30.3% and stable electroluminescence spectra over a wide brightness range.

9.
Math Phys Anal Geom ; 27(3): 10, 2024.
Article in English | MEDLINE | ID: mdl-38911699

ABSTRACT

We compute the deterministic approximation for mixed fluctuation moments of products of deterministic matrices and general Sobolev functions of Wigner matrices. Restricting to polynomials, our formulas reproduce recent results of Male et al. (Random Matrices Theory Appl. 11(2):2250015, 2022), showing that the underlying combinatorics of non-crossing partitions and annular non-crossing permutations continue to stay valid beyond the setting of second-order free probability theory. The formulas obtained further characterize the variance in the functional central limit theorem given in the recent companion paper (Reker in Preprint, arXiv:2204.03419, 2023). and thus allow identifying the fluctuation around the thermal value in certain thermalization problems.

10.
Front Microbiol ; 15: 1410368, 2024.
Article in English | MEDLINE | ID: mdl-38873146

ABSTRACT

Ganoderic acids (GAs) are major functional components of Ganoderma lucidum. The study aimed to breed a new G. lucidum strain with increased contents of individual GAs. Two mating-compatible monokaryotic strains, G. 260125 and G. 260124, were successfully isolated from the dikaryotic G. lucidum CGMCC 5.0026 via protoplast formation and regeneration. The Vitreoscilla hemoglobin gene (vgb) and squalene synthase gene (sqs) were overexpressed in the monokaryotic G. 260124 and G. 260125 strain, respectively. Mating between the G. 260124 strain overexpressing vgb and the G. 260125 strain overexpressing sqs resulted in the formation of the new hybrid dikaryotic G. lucidum strain sqs-vgb. The maximum contents of ganoderic acid (GA)-T, GA-Me, and GA-P in the fruiting body of the mated sqs-vgb strain were 23.1, 15.3, and 39.8 µg/g dry weight (DW), respectively, 2.23-, 1.75-, and 2.69-fold greater than those in G. lucidum 5.0026. The squalene and lanosterol contents increased 2.35- and 1.75-fold, respectively, in the fruiting body of the mated sqs-vgb strain compared with those in the G. lucidum 5.0026. In addition, the maximum expression levels of the sqs and lanosterol synthase gene (ls) were increased 3.23- and 2.13-fold, respectively, in the mated sqs-vgb strain. In summary, we developed a new G. lucidum strain with higher contents of individual GAs in the fruiting body by integrating genetic engineering and mono-mono crossing.

11.
Traffic Inj Prev ; : 1-7, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833267

ABSTRACT

OBJECTIVE: Child pedestrian injuries are a significant public health problem, largely because children have underdeveloped cognitive-perceptual capacity to judge traffic unsupervised. This study used a virtual reality (VR) environment to examine the impact of children's age, as well as sex and sensation-seeking personality, on pedestrian behavior in different risk contexts. METHODS: 405 Norwegian children (7-10-year-olds) engaged in street-crossing scenarios within a VR environment. Children crossed a bicycle path and urban roadway six times, each with increasing density and complexity of traffic. Hits and near hits were recorded. Self-reported sensation-seeking personality was assessed. RESULTS: Children were more likely to experience crashes in the tasks that offered higher probability risk. Overall, 106 children crossed safely in all tasks. Dangerous crossings were associated with male sex, higher thrill and intensity seeking personality, and denser traffic. Age was not related to any traffic safety outcomes. CONCLUSION: As expected, children were struck by vehicles more often in complex traffic contexts than in less complex ones. The results support previous findings and suggest that boys and sensation seekers have elevated risk of pedestrian injury, and that individual differences in children, rather than age alone, must be considered when determining if children are capable of safely negotiating traffic unsupervised.

12.
Chromosoma ; 133(2): 93-115, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38730132

ABSTRACT

Meiosis is the specialized cellular program that underlies gamete formation for sexual reproduction. It is therefore not only interesting but also a fundamentally important subject for investigation. An especially attractive feature of this program is that many of the processes of special interest involve organized chromosomes, thus providing the possibility to see chromosomes "in action". Analysis of meiosis has also proven to be useful in discovering and understanding processes that are universal to all chromosomal programs. Here we provide an overview of the different historical moments when the gap between observation and understanding of mechanisms and/or roles for the new discovered molecules was bridged. This review reflects also the synergy of thinking and discussion among our three laboratories during the past several decades.


Subject(s)
Meiosis , Humans , Animals , History, 20th Century , History, 21st Century , History, 19th Century , Chromosomes/genetics
13.
Hum Mov Sci ; 95: 103223, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692198

ABSTRACT

Older adults have a decreased trunk movement control which is linked to their higher fall risk. While motor/cognitive dual-tasking deteriorates balance and walking in older adults, there is limited understanding on how trunk kinematics and kinetics are affected by dual-tasking in scenarios where falls can occur. Therefore, the purpose of the study was to determine the impacts of a challenging motor dual-task, specifically obstacle avoidance during walking, on trunk and lower-body kinematics and kinetics of older adults compared to young adults. The study captured three-dimensional kinematic and kinetic data from 12 young adults and 10 older adults as they walked on a treadmill and stepped over an obstacle with both legs. The study analyzed trunk, hip, knee, and ankle angles and torques. Trunk torque was further broken down to trunk muscle torque, gravitational torque, and inertia torque. A linear mixed effects model was used to investigate the difference in each variable between the two groups. Older adults exhibited significantly increased trunk flexion angle and trunk extension muscle torque compared to young adults, with the trunk being the only segment/joint showing differences in both kinematics and kinetics. Trunk torque breakdown analysis revealed that larger trunk flexion led to a larger gravitational torque, which contributed to an increased compensatory trunk muscle torque. Moreover, older adults' less controlled trunk flexion during weight shifting from trail leg to the lead leg, necessitated a compensatory trunk deceleration during trail leg obstacle avoidance which was achieved by generating additional increase in trunk muscle torque. The study demonstrated that motor dual-tasking has the most negative effects on trunk control in older adults compared to young adults. This exposes older adults to a higher fall risk. Therefore, future work should focus on supporting trunk control during daily multi-tasking conditions where falls can occur.


Subject(s)
Postural Balance , Torso , Walking , Humans , Biomechanical Phenomena/physiology , Aged , Male , Female , Torso/physiology , Walking/physiology , Postural Balance/physiology , Adult , Young Adult , Torque , Accidental Falls , Psychomotor Performance/physiology , Movement/physiology , Muscle, Skeletal/physiology , Aging/physiology
14.
J Mol Model ; 30(6): 186, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801631

ABSTRACT

CONTEXT: Three donor (D)-acceptor (A)-type temperature-activated delayed fluorescent (TADF) molecules of 9-(2-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9H-3,9'-bicarbazole (o-TrzDCz), 9-(3-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9H-3,9'-bicarbazole (m-TrzDCz), and 9-(4-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9H-3,9'-bicarbazole (p-TrzDCz) were designed in this paper, and the photophysical properties, including the intersystem crossing rate, the reorganization energies (λ), and the intersystem crossing/reverse intersystem crossing (ISC/RISC) rate, were simulated to explore the effect of substitution sites on their TADF character. The values of the twist angle between the D and A moieties in ground state and the molecular root-mean-square deviation (RMSD) of the S1 and T1 states referenced to the S0 state indicate that o-TrzDCz possess bigger steric hindrance and stabler molecular configuration. The λ values of the ISC/RISC process should be 0.06/0.04 eV for o-TrzDCz, which are much smaller than those of m-TrzDCz (0.51/0.41 eV) and p-TrzDCz (1.93/1.06 eV). At the same time, o-TrzDCz possess the biggest kRISC (7.28 × 106 s-1) and kr (3.12 × 106 s-1) values and the smallest kp (0.10 s-1) value among the three titled molecules. These data indicate that o-TrzDCz should have more excellent TADF character than m-TrzDCz and p-TrzDCz. In a word, this research presents that adjusting the molecular linking manner should be a charming way to explore novel high-efficient TADF molecules. METHODS: Quantum chemical calculations were performed at PBE0/6-31G* level by Gaussian 09 and ORCA 4.1.0 software packages, and reorganization energies and Huang-Rhys were performed by the DUSHIN program and MOMAP 2019B software package based on the Gaussian 09 output files, while the phosphorescence rates were performed at B3LYP/6-31G* level by Dalton 2021.

15.
BMC Chem ; 18(1): 104, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807212

ABSTRACT

Ten novel spectrophotometric approaches were developed for the initial examination of the Hydroxychloroquine and Paracetamol medications. These procedures are straightforward, specific, easy to use, and provide exact and accurate results. The determination was conducted through the utilization of several approaches, including zero order (dual wavelength, zero crossing, advanced absorption subtraction and spectrum subtraction), derivative (first derivative of zero crossing), ratio (ratio difference, ratio derivative) and mathematical (bivariate, simultaneous equation, and Q-absorbance) techniques. After undergoing validation in accordance with ICH criteria, it was established that each of these methods achieved acceptable levels of precision, repeatability, robustness, and accuracy. The advantages and disadvantages of each method are demonstrated, and the proposed and reported methodologies were statistically compared.

16.
Microbiol Spectr ; 12(6): e0069024, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38752731

ABSTRACT

Enterovirus A71 (EV-A71) is associated with neurological conditions such as acute meningitis and encephalitis. The virus is detected in the bloodstream, and high blood viral loads are associated with central nervous system (CNS) manifestations. We used an in vitro blood-brain barrier (BBB) model made up of human brain-like endothelial cells (hBLECs) and brain pericytes grown in transwell systems to investigate whether three genetically distinct EV-A71 strains (subgenogroups C1, C1-like, and C4) can cross the human BBB. EV-A71 poorly replicated in hBLECs, which released moderate amounts of infectious viruses from their luminal side and trace amounts of infectious viruses from their basolateral side. The barrier properties of hBLECs were not impaired by EV-A71 infection. We investigated the passage through hBLECs of EV-A71-infected white blood cells. EV-A71 strains efficiently replicated in immune cells, including monocytes, neutrophils, and NK/T cells. Attachment to hBLECs of immune cells infected with the C1-like virus was higher than attachment of cells infected with C1-06. EV-A71 infection did not impair the transmigration of immune cells through hBLECs. Overall, EV-A71 targets different white blood cell populations that have the potential to be used as a Trojan horse to cross hBLECs more efficiently than cell-free EV-A71 particles.IMPORTANCEEnterovirus A71 (EV-A71) was first reported in the USA, and numerous outbreaks have since occurred in Asia and Europe. EV-A71 re-emerged as a new multirecombinant strain in 2015 in Europe and is now widespread. The virus causes hand-foot-and-mouth disease in young children and is involved in nervous system infections. How the virus spreads to the nervous system is unclear. We investigated whether white blood cells could be infected by EV-A71 and transmit it across human endothelial cells mimicking the blood-brain barrier protecting the brain from adverse effects. We found that endothelial cells provide a strong roadblock to prevent the passage of free virus particles but allow the migration of infected immune cells, including monocytes, neutrophils, and NK/T cells. Our data are consistent with the potential role of immune cells in the pathogenesis of EV-A71 infections by spreading the virus in the blood and across the human blood-brain barrier.


Subject(s)
Blood-Brain Barrier , Endothelial Cells , Enterovirus A, Human , Enterovirus Infections , Blood-Brain Barrier/virology , Humans , Enterovirus A, Human/genetics , Enterovirus A, Human/physiology , Enterovirus Infections/virology , Enterovirus Infections/immunology , Endothelial Cells/virology , Virus Replication , Monocytes/virology , Monocytes/immunology , Pericytes/virology , Leukocytes/virology , Leukocytes/immunology , Brain/virology , Killer Cells, Natural/immunology , Neutrophils/immunology , Neutrophils/virology
17.
Chemistry ; 30(39): e202400733, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38758636

ABSTRACT

The Psoralen (Pso) molecule finds extensive applications in photo-chemotherapy, courtesy of its triplet state forming ability. Sulfur and selenium replacement of exocyclic carbonyl oxygen of organic chromophores foster efficient triplet harvesting with near unity triplet quantum yield. These triplet-forming photosensitizers are useful in Photodynamic Therapy (PDT) applications for selective apoptosis of cancer cells. In this work, we have critically assessed the effect of the sulfur and selenium substitution at the exocyclic carbonyl (TPso and SePso, respectively) and endocyclic oxygen positions of Psoralen. It resulted in a significant redshifted absorption spectrum to access the PDT therapeutic window with increased oscillator strength. The reduction in singlet-triplet energy gap and enhancement in the spin-orbit coupling values increase the number of intersystem crossing (ISC) pathways to the triplet manifold, which shortens the ISC lifetime from 10-5 s for Pso to 10-8 s for TPso and 10-9 s for SePso. The intramolecular photo-induced electron transfer process, a competitive pathway to ISC, is also considerably curbed by exocyclic functionalizations. In addition, a maximum of 115 GM of two-photon absorption (2PA) with IR absorption (660-1050 nm) confirms that the Psoralen skeleton can be effectively tweaked via single chalcogen atom replacement to design a suitable PDT photosensitizer.


Subject(s)
Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photochemotherapy/methods , Humans , Selenium/chemistry , Ficusin/chemistry , Ficusin/pharmacology , Sulfur/chemistry
18.
J Comput Chem ; 45(23): 2034-2041, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38733370

ABSTRACT

The outcomes of DFT-based calculations are here reported to assess the applicability of two synthesized polypyridyl Ru(II) complexes, bearing ethynyl nile red (NR) on a bpy ligand, and two analogues, bearing modified-NR, in photodynamic therapy. The absorption spectra, together with the non-radiative rate constants for the S1 - Tn intersystem crossing transitions, have been computed for this purpose. Calculations evidence that the structural modification on the chromophore destabilizes the HOMO of the complexes thus reducing the H-L gap and, consequently, red shifting the maximum absorption wavelength within the therapeutic window, up to 620 nm. Moreover, the favored ISC process from the bright state involves the triplet state closest in energy, which is also characterized by the highest SOC value and by the involvement of the whole bpy ligand bearing the chromophore in delocalising the unpaired electrons. These outcomes show that the photophysical behavior of the complexes is dominated by the chromophore.

19.
Chemistry ; : e202401084, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819870

ABSTRACT

The link of an antenna dye with an electron spin converter, in this case naphthalenediimide and C60, produces a system with a rich photophysics including the detection of more than one triplet state on the long timescale (tens of µs). Beside the use of optical spectroscopies in the ns and in the fs time scale, we used time-resolved Electron Paramagnetic Resonance (TREPR) to study the system evolution following photoexcitation. TREPR keeps track of the formation path of the triplet states through specific spin polarization patterns observed in the spectra. The flexibility of the linker and solvent polarity play a role in favouring either electron transfer or energy transfer processes.

20.
ACS Appl Mater Interfaces ; 16(22): 29324-29337, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38776974

ABSTRACT

Triplet-triplet annihilation upconversion (TTA-UC) implemented in nanoparticle assemblies is of emerging interest in biomedical applications, including in drug delivery and imaging. As it is a bimolecular process, ensuring sufficient mobility of the sensitizer and annihilator to facilitate effective collision in the nanoparticle is key. Liposomes can provide the benefits of two-dimensional confinement and condensed concentration of the sensitizer and annihilator along with superior fluidity compared to other nanoparticle assemblies. They are also biocompatible and widely applied across drug delivery modalities. However, there are relatively few liposomal TTA-UC systems reported to date, so systematic studies of the influence of the liposomal environment on TTA-UC are currently lacking. Here, we report the first example of a BODIPY-based sensitizer TTA-UC system within liposomes and use this system to study TTA-UC generation and compare the relative intensity of the anti-Stokes signal for this system as a function of liposome composition and membrane fluidity. We report for the first time on time-resolved spectroscopic studies of TTA-UC in membranes. Nanosecond transient absorption data reveal the BODIPY-perylene dyad sensitizer has a long triplet lifetime in liposome with contributions from three triplet excited states, whose lifetimes are reduced upon coinclusion of the annihilator due to triplet-triplet energy transfer, to a greater extent than in solution. This indicates triplet energy transfer between the sensitizer and the annihilator is enhanced in the membrane system. Molecular dynamics simulations of the sensitizer and annihilator TTA collision complex are modeled in the membrane and confirm the co-orientation of the pair within the membrane structure and that the persistence time of the bound complex exceeds the TTA kinetics. Modeling also reliably predicted the diffusion coefficient for the sensitizer which matches closely with the experimental values from fluorescence correlation spectroscopy. The relative intensity of the TTA-UC output across nine liposomal systems of different lipid compositions was explored to examine the influence of membrane viscosity on upconversion (UC). UC showed the highest relative intensity for the most fluidic membranes and the weakest intensity for highly viscous membrane compositions, including a phase separation membrane. Overall, our study reveals that the co-orientation of the UC pair within the membrane is crucial for effective TTA-UC within a biomembrane and that the intensity of the TTA-UC output can be tuned in liposomal nanoparticles by modifying the phase and fluidity of the liposome. These new insights will aid in the design of liposomal TTA-UC systems for biomedical applications.


Subject(s)
Boron Compounds , Liposomes , Liposomes/chemistry , Boron Compounds/chemistry , Nanoparticles/chemistry , Membrane Fluidity
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