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1.
Nat Commun ; 15(1): 6084, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030160

RESUMO

Tuning the properties of a pair of entangled electron and hole in a light-induced exciton is a fundamentally intriguing inquiry for quantum science. Here, using semiconducting hybrid perovskite as an exploratory platform, we discover that Nd2+-doped CH3NH3PbI3 (MAPbI3) perovskite exhibits a Kondo-like exciton-spin interaction under cryogenic and photoexcitation conditions. The feedback to such interaction between excitons in perovskite and the localized spins in Nd2+ is observed as notably prolonged carrier lifetimes measured by time-resolved photoluminescence, ~10 times to that of pristine MAPbI3 without Nd2+ dopant. From a mechanistic standpoint, such extended charge separation states are the consequence of the trap state enabled by the antiferromagnetic exchange interaction between the light-induced exciton and the localized 4 f spins of the Nd2+ in the proximity. Importantly, this Kondo-like exciton-spin interaction can be modulated by either increasing Nd2+ doping concentration that enhances the coupling between the exciton and Nd2+ 4 f spins as evidenced by elongated carrier lifetime, or by using an external magnetic field that can nullify the spin-dependent exchange interaction therein due to the unified orientations of Nd2+ spin angular momentum, thereby leading to exciton recombination at the dynamics comparable to pristine MAPbI3.

2.
Sci Rep ; 14(1): 16687, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030390

RESUMO

This study compared the safety of general anesthesia (GA) and intravenous sedation (IVS) in patients who underwent extraction of one or more third molars. Data from 1260 patients (GA group, n = 1043; IVS group, n = 217) were retrospectively analyzed, including demographics, preoperative data, intraoperative hemodynamic parameters (blood pressure, heart rate, and oxygen saturation level), and medications administered intraoperatively and postoperatively. The incidence of intraoperative circulatory variations, surgery and anesthesia durations, postoperative complications, and medication use were assessed and compared. The GA group had longer anesthesia and surgery durations, a higher incidence of hypotension, and a higher frequency of postoperative analgesic use than the IVS group. Dexmedetomidine was the most frequently used sedative agent. The IVS group had a lower incidence of intraoperative hypotension but they had a higher need for vasopressors in the recovery room. Both anesthesia methods maintained satisfactory oxygen saturation levels and sufficient anesthesia throughout the procedure, but they showed different characteristics regarding the duration of surgery and anesthesia duration, hemodynamic stability, and postoperative analgesic needs. IVS may be preferable for patients at risk of cardiovascular complications such as hypotension or tachycardia during surgery.


Assuntos
Anestesia Geral , Dente Serotino , Extração Dentária , Humanos , Anestesia Geral/métodos , Feminino , Masculino , Extração Dentária/efeitos adversos , Extração Dentária/métodos , Dente Serotino/cirurgia , Adulto , Estudos Retrospectivos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Adulto Jovem , Hemodinâmica/efeitos dos fármacos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Pessoa de Meia-Idade
3.
Oncology ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39053443

RESUMO

INTRODUCTION: Reactive oxygen species modulator 1 (Romo1) is a novel protein that is critically involved in intracellular production of reactive oxygen species. Evidence revealed that Romo1 is related with treatment outcomes of various human malignancies including lung cancer. However, clinical implication of this protein in surgically-resected lung cancer harboring the epidermal growth factor receptor (EGFR) mutation has not been investigated. METHODS: Data were collected from the patients who underwent curative resection for EGFR-mutant lung adenocarcinoma. Romo1 protein expression level was measured in the resected tumor tissue using immunohitochemical staining and evaluated semiquantatively using histochemical score (H score). Univariate and multivariate analyses were performed to identify clinicopathological parameters that may be associated with clinical outcomes. RESULTS: A total of 98 samples were analyzed. Using the cutoff H score 150, the population was classified into low (n=73) and high (n=25) Romo1 groups. Romo1 expression was significantly higher in smokers, patients with stage III disease, and patient who experienced recurrence after surgery (all p<0.05). In the multivariate analyses, advanced stage and poorly differentiated cancer were associated with shorter disease-free survival (DFS). In addition, high Romo1 expression was independently associated with poor DFS (hazard ratio [HR] = 2.20, 95% confidence interval [CI]:1.10-5.42, p = 0.0324). CONCLUSIONS: Our data showed that Romo1 overexpression was significantly associated with early recurrence in patients with resected, EGFR-mutant lung adenocarcinoma. Although large-scaled data are needed, Romo1 may have prognostic role for this patient population.

4.
Sci Robot ; 9(91): eadk3925, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865475

RESUMO

Electrotactile stimulus is a form of sensory substitution in which an electrical signal is perceived as a mechanical sensation. The electrotactile effect could, in principle, recapitulate a range of tactile experience by selective activation of nerve endings. However, the method has been plagued by inconsistency, galvanic reactions, pain and desensitization, and unwanted stimulation of nontactile nerves. Here, we describe how a soft conductive block copolymer, a stretchable layout, and concentric electrodes, along with psychophysical thresholding, can circumvent these shortcomings. These purpose-designed materials, device layouts, and calibration techniques make it possible to generate accurate and reproducible sensations across a cohort of 10 human participants and to do so at ultralow currents (≥6 microamperes) without pain or desensitization. This material, form factor, and psychophysical approach could be useful for haptic devices and as a tool for activation of the peripheral nervous system.


Assuntos
Elastômeros , Condutividade Elétrica , Psicofísica , Tato , Humanos , Tato/fisiologia , Adulto , Feminino , Masculino , Desenho de Equipamento , Estimulação Elétrica , Adulto Jovem , Polímeros , Eletrodos , Calibragem , Percepção do Tato/fisiologia
6.
Ophthalmol Glaucoma ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705275

RESUMO

PURPOSE: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DESIGN: Retrospective, longitudinal, observational study. PARTICIPANTS: Ninety-five patients with unilateral NTG and 61 healthy controls. METHODS: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable retinal nerve fiber layer thickness (RNFLT) measurements were performed using OCT. Factors associated with the rate of thinning of the unaffected eyes of unilateral patients with NTG were identified using regression analysis. MAIN OUTCOME MEASURES: The rate of progressive RNFL thinning and the associated factors. RESULTS: Retinal nerve fiber layer thickness decreased significantly in both the unaffected eyes of unilateral patients with NTG and the healthy eyes (both P < 0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral patients with NTG than in the healthy eyes (P < 0.001), specifically in the temporal-inferior (TI) sector (P = 0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral patients with NTG were thicker baseline RNFL of the unaffected eyes (P = 0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P = 0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P = 0.007). CONCLUSIONS: The unaffected eyes of unilateral patients with NTG showed faster RNFL thinning than healthy control eyes, more obviously in the TI sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral patients with NTG, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

7.
HGG Adv ; 5(3): 100301, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38773773

RESUMO

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.


Assuntos
Gêmeos Dizigóticos , Sequenciamento Completo do Genoma , Zigoto , Humanos , Feminino , Gêmeos Dizigóticos/genética , Zigoto/metabolismo , Gravidez , Quimerismo , Placenta/metabolismo , Masculino , Quimera/genética , Gêmeos Monozigóticos/genética
8.
Eur J Med Chem ; 272: 116454, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704937

RESUMO

Increasing antibiotic resistance of bacterial pathogens poses a serious threat to human health worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most deleterious bacterial pathogens owing to its multidrug resistance, necessitating the development of new antibacterial agents against it. We previously identified a novel dioxonaphthoimidazolium agent, c5, with moderate antibacterial activity against MRSA from an anticancer clinical candidate, YM155. In this study, we aimed to design and synthesize several novel cationic amphiphilic N1,N3-dialkyldioxonaphthoimidazolium bromides with enhanced lipophilicity of the two side chains in the imidazolium scaffold and improved antibacterial activities compared to those of c5 against gram-positive bacteria in vitro and in vivo. Our new antibacterial lead, N1,N3-n-octylbenzyldioxonaphthoimidazolium bromide (11), exhibited highly potent antibacterial activities against various gram-positive bacterial strains (MICs: 0.19-0.39 µg/mL), including MRSA, methicillin-sensitive S. aureus, and Bacillus subtilis. Moreover, antibacterial mechanism of 11 against MRSA based on the generation of reactive oxygen species (ROS) was evaluated. Although compound 11 exhibited cytotoxic effects in vitro and lacked a therapeutic index against the HEK293 and HDFa mammalian cell lines, it exhibited low toxicity in the Drosophila animal model. Remarkably, 11 exhibited better in vivo antibacterial efficacy than c5 and the clinically used antibiotic, vancomycin, in SA3-infected Drosophila model. Moreover, the development of bacterial resistance to 11 was not observed after 16 consecutive passages. Therefore, rational design of antibacterial cationic amphiphiles based on ROS-generating pharmacophores with optimized lipophilicity can facilitate the identification of potent antibacterial agents against drug-resistant infections.


Assuntos
Antibacterianos , Desenho de Fármacos , Imidazóis , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Imidazóis/farmacologia , Imidazóis/química , Imidazóis/síntese química , Relação Estrutura-Atividade , Humanos , Estrutura Molecular , Relação Dose-Resposta a Droga , Peixe-Zebra , Espécies Reativas de Oxigênio/metabolismo
9.
Neurol Sci ; 45(7): 3513-3516, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38589770

RESUMO

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants. CASE PRESENTATION: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient's brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance. DISCUSSION AND PERSPECTIVE: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.


Assuntos
Telas Cirúrgicas , Titânio , Estimulação Transcraniana por Corrente Contínua , Humanos , Feminino , Estimulação Transcraniana por Corrente Contínua/métodos , Estado Vegetativo Persistente/etiologia , Estado Vegetativo Persistente/terapia , Pessoa de Meia-Idade , Transtornos da Consciência/etiologia , Transtornos da Consciência/terapia
10.
Environ Int ; 185: 108534, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38458115

RESUMO

Natural purification of pollutants is highly recognized as regulating ecosystem services; however, the purification capacity of tidal flats remains largely unknown and/or unquantified. A 60-day mesocosm transplant experiment was conducted in situ to assess the purification capacity of natural tidal flats. We adopted the advanced sediment quality triad approach, monitoring 10 endpoints, including chemical reduction, toxicity changes, and community recoveries. The results indicated that contaminated sediments rapidly recovered over time, particularly > 50% within a day, then slowly recovered up to âˆ¼ 70% in a given period (60 days). A significant early reduction of parent pollutants was evidenced across all treatments, primarily due to active bacterial decomposition. Notably, the presence of benthic fauna and vegetated halophytes in the treatments significantly enhanced the purification of pollutants in both efficacy and efficiency. A forecast linear modeling further suggested additive effects of biota on the natural purification of tidal flats, reducing a full recovery time from 500 to 300 days. Overall, the triad approach with machine learning practices successfully demonstrated quantitative insight into the integrated assessment of natural purification.


Assuntos
Poluentes Ambientais , Metais Pesados , Poluentes Químicos da Água , Ecossistema , Sedimentos Geológicos/química , Biota , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise
11.
J Clin Med ; 13(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38337500

RESUMO

BACKGROUND: The aim of this study was to compare the clinical effectiveness of robot-assisted therapy with that of conventional occupational therapy according to the onset and severity of stroke. METHODS: In this multicenter randomized controlled trial, stroke patients were randomized (1:1) to receive robot-assisted therapy or conventional occupational therapy. The robot-assisted training group received 30 min of robot-assisted therapy twice and 30 min of conventional occupational therapy daily, while the conventional therapy group received 90 min of occupational therapy. Therapy was conducted 5 days/week for 4 weeks. The primary outcome was the Wolf Motor Function Test (WMFT) score after 4 and 8 weeks of therapy. RESULTS: Overall, 113 and 115 patients received robot-assisted and conventional therapy, respectively. The WMFT score after robot-assisted therapy was not significantly better than that after conventional therapy, but there were significant improvements in the Motricity Index (trunk) and the Fugl-Meyer Assessment. After robot-assisted therapy, wrist strength significantly improved in the subacute or moderate-severity group of stroke patients. CONCLUSIONS: Robot-assisted therapy improved the upper-limb functions and activities of daily living (ADL) performance as much as conventional occupational therapy. In particular, it showed signs of more therapeutic effectiveness in the subacute stage or moderate-severity group.

12.
Cell Genom ; 4(2): 100499, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38359788

RESUMO

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.


Assuntos
Rearranjo Gênico , Translocação Genética , Humanos , Animais , Camundongos , Mutação , Genômica , Inversão Cromossômica , Mamíferos
13.
Am J Ophthalmol ; 263: 99-108, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38403100

RESUMO

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.


Assuntos
Lâmina Basilar da Corioide , Pressão Intraocular , Fibras Nervosas , Disco Óptico , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Lâmina Basilar da Corioide/patologia , Disco Óptico/patologia , Disco Óptico/diagnóstico por imagem , Disco Óptico/anatomia & histologia , Feminino , Masculino , Estudos Transversais , Estudos Prospectivos , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Fibras Nervosas/patologia , Adulto , Pressão Intraocular/fisiologia , Idoso , Comprimento Axial do Olho/patologia , Campos Visuais/fisiologia , Voluntários Saudáveis
14.
Sci Rep ; 14(1): 2850, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310134

RESUMO

Transcranial Direct Current Stimulation (tDCS) has benefits for motor rehabilitation in stroke patients, but its clinical application is limited due to inter-individual heterogeneous effects. Recently, optimized tDCS that considers individual brain structure has been proposed, but the utility thereof has not been studied in detail. We explored whether optimized tDCS provides unique electrode positions for each patient and creates a higher target electric field than the conventional approach. A comparative within-subject simulation study was conducted using data collected for a randomized controlled study evaluating the effect of optimized tDCS on upper extremity function in stroke patients. Using Neurophet tES LAB 3.0 software, individual brain models were created based on magnetic resonance images and tDCS simulations were performed for each of the conventional and optimized configurations. A comparison of electrode positions between conventional tDCS and optimized tDCS was quantified by calculation of Euclidean distances. A total of 21 stroke patients were studied. Optimized tDCS produced a higher electric field in the hand motor region than conventional tDCS, with an average improvement of 20% and a maximum of 52%. The electrode montage for optimized tDCS was unique to each patient and exhibited various configurations that differed from electrode placement of conventional tDCS. Optimized tDCS afforded a higher electric field in the target of a stroke patient compared to conventional tDCS, which was made possible by appropriately positioning the electrodes. Our findings may encourage further trials on optimized tDCS for motor rehabilitation after stroke.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Acidente Vascular Cerebral/terapia , Encéfalo/fisiologia , Simulação por Computador , Eletrodos
15.
ACS Appl Mater Interfaces ; 16(8): 10238-10250, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38372639

RESUMO

The electrochemical conversion of oxygen holds great promise in the development of sustainable energy for various applications, such as water electrolysis, regenerative fuel cells, and rechargeable metal-air batteries. Oxygen electrocatalysts are needed that are both highly efficient and affordable, since they can serve as alternatives to costly precious-metal-based catalysts. This aspect is particularly significant for their practical implementation on a large scale in the future. Herein, highly porous polyhedron-entrapped metal-organic framework (MOF)-assisted CoTe2/MnTe2 heterostructure one-dimensional nanorods were initially synthesized using a simple hydrothermal strategy and then transformed into ZIF-67 followed by tellurization which was used as a bifunctional electrocatalyst for both the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). The designed MOF CoTe2/MnTe2 nanorod electrocatalyst exhibited superior activity for both OER (η = 220 mV@ 10 mA cm-2) and ORR (E1/2 = 0.81 V vs RHE) and outstanding stability. The exceptional achievement could be primarily credited to the porous structure, interconnected designs, and deliberately created deficiencies that enhanced the electrocatalytic activity for the OER/ORR. This improvement was predominantly due to the enhanced electrochemical surface area and charge transfer inherent in the materials. Therefore, this simple and cost-effective method can be used to produce highly active bifunctional oxygen electrocatalysts.

16.
Uisahak ; 32(3): 1005-1041, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38273727

RESUMO

This paper analyzes the motivations of the British biochemist Joseph Needham for participating in 'the International Scientific Commission for the Investigation of the Facts Concerning Bacterial Warfare in Korea and China (ISC)' and his major roles within it during the Korean War. Needham stayed in China for four years starting in 1942 as a scientific counselor and director of the British Scientific Mission in China, which enabled him to interact with many Chinese scientists and politicians. Surprisingly, during this period (1944), Needham conducted an investigation into the Japanese military's use of bacterial warfare. Through his personal records, Needham repeatedly stated that his experience with bacterial warfare research in 1944 was one of the most important reasons for his participation in ISC activities. In addition, Needham secretly but very actively sought to recruit other investigators within Britain. Needham repeatedly tried to persuade fellow professors at Cambridge University, William Thorpe and Vincent Wigglesworth, to be included in the investigation team. Although Needham had doubts about his own expertise in investigative activities, he actively expressed his desire to become a member of the investigative team through various channels. Primary documents show that he actively and voluntarily led the investigation activities after joining the team in professional discussions, document analysis, and witness interrogations. Needham's passion and sincerity demonstrated in internal meeting minutes dispel some misunderstandings that the investigation team's activities were limited to passively approving Chinese data.


Assuntos
Guerra Biológica , Guerra da Coreia , Humanos , Masculino , Motivação , Coreia (Geográfico) , Emoções
18.
Bioorg Chem ; 144: 107109, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219480

RESUMO

Herein, (-)-galiellalactone 1 congeners responsible for the nuclear factor erythroid 2-related factor 2 (Nrf2)-activating neuroprotective effects were elucidated. Additionally, novel congener-based Nrf2 activators were identified using a drug repositioning strategy. (-)-Galiellalactone, which comprises a tricyclic lactone skeleton, significantly activates antioxidant response element (ARE)-mediated transcription in neuroblastoma SH-SY5Y cells. Interestingly, two cyclohexene-truncated [3.3] bicyclic lactone analogs, which possess an exocyclic α-methylene-γ-butyrolactone moiety, exhibited higher Nrf2/ARE transcriptional activities than the parent (-)-galiellalactone. We confirmed that the cyclohexene moiety embedding the [3.3] bicyclic lactone congener does not play the essential role of (-)-galiellalactone for Nrf2/ARE activation. Nrf2/ARE activation by novel analogs resulted in the upregulation of downstream antioxidative and phase II detoxifying enzymes, heme oxygenase-1, and NAD(P)H quinone oxidoreductase 1, which are closely related to the cytoprotective effects on neurodegenerative diseases. (-)-Galiellalactone and its [3.3] bicyclic variants 3l and 3p increased the expression of antioxidant genes and exhibited neuroprotective effects against 6-hydroxydopamine-mediated neurotoxicity in the neuroblastoma SH-SY5Y cell line.


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais , Neuroblastoma/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Lactonas/farmacologia , Lactonas/química , Cicloexenos/farmacologia , Estresse Oxidativo , Linhagem Celular Tumoral
19.
Br J Ophthalmol ; 108(3): 357-365, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36690420

RESUMO

BACKGROUND/AIMS: To compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary ß-zones and γ-zones. METHODS: 294 eyes with primary open-angle glaucoma (POAG) and parapapillary atrophy (PPA) underwent optical coherence tomography (OCT) to determine the type of PPA and OCT angiography scanning of the optic nerve head to determine the presence of cMvD. Eyes were classified based on the type of PPA (ß-zones and γ-zones), and their clinical characteristics were compared. Factors associated with the rate of rapid progressive RNFL thinning were determined in each group, including the presence of cMvD as an independent variable. RESULTS: Of the 294 eyes, 186 and 108 were classified as having ß-zones and γ-zones, respectively. The rate of RNFL thinning was slower (p<0.001), axial length was longer (p<0.001) and presence of cMvD was less frequent (57.4% vs 73.1%, p=0.006) in eyes with γ-zone than those with ß-zone. Multivariate analyses showed that greater lamina cribrosa curvature (p=0.047) and the presence of cMvD (p=0.010) were associated with a faster rate of RNFL thinning in eyes with ß-zone, whereas larger intraocular pressure fluctuation (p<0.001), shorter axial length (p=0.042) and greater baseline RNFL thickness (p<0.001) were associated with a faster rate of RNFL thinning in eyes with γ-zone. CONCLUSIONS: The presence of cMvD was significantly associated with a faster rate of RNFL thinning in POAG eyes with ß-zone, but not γ-zone. The pathogenic consequences of cMvD in POAG eyes may depend on accompanying peripapillary structures.


Assuntos
Glaucoma de Ângulo Aberto , Humanos , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/patologia , Campos Visuais , Células Ganglionares da Retina/patologia , Pressão Intraocular , Tomografia de Coerência Óptica/métodos , Atrofia , Microvasos/patologia , Fibras Nervosas/patologia
20.
J Cataract Refract Surg ; 50(4): 328-332, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37919836

RESUMO

PURPOSE: To compare the posterior capsule rupture (PCR) rates of cataract surgery using a traditional ophthalmic surgical microscope (OSM) and a 3D heads-up visualization system (HUVS). SETTING: Single tertiary referral center. DESIGN: Retrospective study. METHODS: This study included 10 101 eyes that underwent phacoemulsification cataract surgery. Surgeries were performed using either 3D HUVS (1964 eyes, performed by 2 surgeons, HUVS group) or traditional OSM (8137 eyes, performed by 6 surgeons, OSM group) from February 2018 to June 2022. Data were collected based on the diagnosis-related group system, and the rate of PCR requiring vitrectomy and the surgical time were evaluated. RESULTS: The PCR rates were not significantly different between the OSM (n = 63; 0.7%) and HUVS (n = 19; 0.9%, P = .392) groups. The mean surgical time was significantly longer in the HUVS group (14.7 ± 10.6 minutes) than in the OSM group (12.9 ± 9.9 minutes, P < .001). In the 3D HUVS group, there were no PCR cases among the initial 100 patients. In both groups, no significant difference was observed in the PCR rates over time. Although the difference was not statistically significant, the PCR rate decreased over time in the HUVS group. CONCLUSIONS: The results indicate that 3D HUVS-based cataract surgery performed by experienced cataract surgeons had a PCR rate similar to that of traditional OSM-based surgery during the 4-year study period. Although the surgical time was slightly longer with 3D HUVS, cataract surgery using 3D HUVS can be performed safely by experienced surgeons.


Assuntos
Extração de Catarata , Catarata , Facoemulsificação , Humanos , Facoemulsificação/métodos , Estudos Retrospectivos , Extração de Catarata/métodos , Vitrectomia
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