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Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic-pituitary-gonadal axis in mammals to trigger the juvenile-adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.
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Proteínas de Drosophila , Drosophila melanogaster , Hormônios de Inseto , Neurônios , Receptores de Esteroides , Comportamento Sexual Animal , Animais , Drosophila melanogaster/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Comportamento Sexual Animal/fisiologia , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Neurônios/fisiologia , Neurônios/metabolismo , Hormônios de Inseto/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Ecdisona/metabolismo , Metamorfose Biológica/fisiologia , Masculino , Larva/crescimento & desenvolvimento , Larva/fisiologia , Proteínas de InsetosRESUMO
Alcohol abuse, also known as Alcohol Use Disorder (AUD), is a substance dependency psychiatric disorder. We aimed to establish a causal relationship between specific gut microbiota and alcohol abuse using Mendelian Randomisation (MR) and bioinformatics methods. We acquired summary data of genome-wide association studies (GWAS) for gut microbiota and alcohol abuse from the Mibiogen and Finngen databases, respectively. We conducted MR analyses using various methodologies and mapped the single nucleotide polymorphisms (SNPs) to genes via the FUMA GWAS platform. We further performed multiple enrichment analyses and a Multi-variable Mendelian Randomisation (MVMR) approach to examine whether gut microbiota influences alcohol abuse by modulating neurotransmitter-related amino acids. The MR analysis revealed an inverse relationship between the genus Eubacterium ventriosum group and the Porphyromonadaceae family with alcohol abuse. Gene enrichment analysis showed that these genes are expressed in brain tissue and are involved in addictive disorders, psychiatric conditions, immunological processes, neurotransmitter synthesis and synaptic regulation. MVMR analysis suggested that the Porphyromonadaceae family as well as genus Eubacterium ventriosum group may suppress alcohol abuse through the metabolism of neurotransmitter-related amino acids, especially Tryptophan. The MR analysis and bioinformatics investigations indicate that the genus Eubacterium ventriosum group and Porphyromonadaceae family confer a protective effect against alcohol abuse, potentially through the modulation of synaptic function.
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Alcoolismo , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Alcoolismo/genética , Alcoolismo/microbiologia , Humanos , Polimorfismo de Nucleotídeo Único , Biologia Computacional/métodos , Estudo de Associação Genômica AmplaRESUMO
Mopeds are a popular mode of transportation in Taiwan, yet collision accidents often lead to abrasion requiring medical attention. While hydrofiber foam dressing (HFD) have proven to help control exudates, reduce the frequency of dressing changes, and preserve more viable tissue, there is currently no established clinical guideline for the treatment of abrasion wounds with dressings. Therefore, the aim of this study was to investigate the clinical outcomes of abrasions treated with hydrofiber foam dressings. A total of 127 patients treated with HFDs between June 2018 and January 2021 were included in this study. Abrasions were categorized into 3 grades: grade I (nâ =â 0) involving the epidermal layer, grade II (nâ =â 89) involving the dermal layer, and grade III (nâ =â 38) involving subcutaneous layer, bone or tendon. Statistical analysis showed that there was a significant difference in healing time (Pâ <â 0.001) and the number of outpatient department (OPD) visits (Pâ =â 0.013) between grade II and grade III. However, there was no significant difference in the number of dressing pieces used. This study offers a clinical reference for the use of hydrofiber foam dressings in treating different grades of abrasion wounds caused by moped accidents.
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Cicatrização , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Resultado do Tratamento , Taiwan , Bandagens , Adulto Jovem , Acidentes de Trânsito , Idoso de 80 Anos ou mais , AdolescenteRESUMO
The trend in neutron sciences is toward integrating compact, high-brightness moderators into new or upgraded facilities. Transporting neutrons from the source to the sample position with a phase-space distribution tailored to specific requirements is crucial to leverage high source brilliance. We have investigated four guide concepts using Monte Carlo ray tracing simulations: Montel beamline with nested Kirkpatrick-Baez mirrors, curved-tapered beamline with a bender and straight sections, straight-elliptical beamline, and curved-elliptical beamline. The straight-elliptical (curved-elliptical) beamline features two half-ellipse guides connected by a straight (non-straight) guide section. The neutron transport efficiency and phase space homogeneity have been quantitatively compared. Our results show that the straight-elliptical beamline performs best because of few neutron bounces on the guide surface with small reflection angles, minimizing flux loss. The Montel beamline provides the best spatial confinement of neutrons within the desired region; however, there is a high thermal-neutron loss due to large reflection angles. The curved-tapered beamline suffers from significant flux loss due to high bounces, and it shows a non-uniform angular distribution related to broad ranges of bounces and reflection angles. The non-straight guide section of the curved-elliptical beamline increases the phase space inhomogeneity, leading to a spatially non-uniform beam profile. The results apply to general neutron instruments that require transporting thermal and cold neutrons from a compact, high-brilliance moderator to the sample location with a moderate phase-space volume.
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Enhancement of image resolution for scenes captured under extremely dim conditions represents a practical yet challenging problem that has received little attention. In such low-light scenarios, the limited lighting and minimal signal clarity tend to intensify issues such as diminished detail visibility and altered color accuracy, which are often more severe during the image enhancement process than in scenarios with adequate lighting. Consequently, standard methods for enhancing low-light images or improving their resolution, whether implemented independently or through a combined approach, generally face challenges in effectively restoring luminance, preserving color integrity, and detailing intricate features. To conquer these issues, this article introduces an innovative dual-stream (DS) modulated learning framework designed to tackle the real-world coupled degradation issues in super-resolution (SR) under low-light conditions. Leveraging natural image color characteristics, we introduce a self-regularized luminance constraint to specifically target uneven illumination. We develop illumination-semantic dual modulator (ISDM), a refinement middleware embedded in the decoding stage to bridge illumination and semantic features concurrently, aimed at safeguarding the integrity of lighting and color details at the feature level. Our approach replaces simple upsampling methods with the resolution-sensitive merging upsampler (RSMU) module, which integrates diverse sampling techniques to effectively reduce artifacts and halo effects. Comprehensive experiments on three benchmarks showcase the applicability and generalizability of our approach to diverse and challenging ultra-poorly lit settings, outperforming state-of-the-art methods with a notable improvement. The code and benchmark are publicly available at https://github.com/moriyaya/UltraIS.
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The CCN family is a group of matricellular proteins associated with the extracellular matrix. This study aims to explore the role of the CCN family in glioma development and its implications in the tumor microenvironment. Through analysis of bulk RNA-seq cohorts, correlations between CCN family expression and glioma subtypes, patient survival, and bioactive pathway enrichment were investigated. Additionally, single-cell datasets were employed to identify novel cell subgroups, followed by analyses of cell communication and transcription factors. Spatial transcriptomic analysis was utilized to validate the CCN family's involvement in glioma. Results indicate overexpression of CYR61,CTGF, and WISP1 in glioma, associated with unfavorable subtypes and reduced survival. Enrichment analyses revealed associations with oncogenic pathways, while CTGF and WISP1 expression correlated with increased infiltration of regulatory T cells and M2 macrophages. Single-cell analysis identified MES-like cells as the highest CCN expression. Moreover, intercellular signal transduction analysis demonstrated active pathways, including SPP1-CD44, in cell subgroups with elevated CYR61 and CTGF expression. Spatial transcriptomic analysis confirmed co-localization of CYR61,CTGF and SPP1-CD44 with high oncogenic pathway activity. These findings suggest that CCN family members may serve as potential prognostic biomarkers and therapeutic targets for glioma.
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Low-grade glioma (LGG), a common primary tumor, mainly originates from astrocytes and oligodendrocytes. Increasing evidence has shown that peroxisomes function in the regulation of tumorigenesis and development of cancer. However, the prognostic value of peroxisome-related genes (PRGs) in LGG has not been reported. Therefore, it is necessary to construct a prognostic risk model for LGG patients based on the expression profiles of peroxisome-related genes. Our study mainly concentrated on developing a peroxisome-related gene signature for overall survival (OS) prediction in LGG patients. First, according to these peroxisome-related genes, all LGG patients from The Cancer Genome Atlas (TCGA) database could be divided into two subtypes. Univariate Cox regression analysis was used to find prognostic peroxisome-related genes in TCGA_LGG dataset, and least absolute shrinkage and selection operator Cox regression analysis was employed to establish a 14-gene signature. The risk score based on the signature was positively associated with unfavorable prognosis. Then, multivariate Cox regression incorporating additional clinical characteristics showed that the 14-gene signature was an independent predictor of LGG. Time-dependent ROC curves revealed good performance of this prognostic signature in LGG patients. The performance about predicting OS of LGG was validated using the GSE107850 dataset derived from the Gene Expression Omnibus (GEO) database. Furethermore, we constructed a nomogram model based on the gene signature and age, which showed a better prognostic power. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses showed that neuroactive ligand-receptor interaction and phagosome were enriched and that the immune status was decreased in the high-risk group. Finally, cell counting kit-8 (CCK8) were used to detect cell proliferation of U251 and A172 cells. Inhibition of ATAD1 (ATPase family AAA domain-containing 1) and ACBD5 (Acyl-CoA binding-domain-containing-5) expression led to significant inhibition of U251 and A172 cell proliferation. Flow cytometry detection showed that ATAD1 and ACBD5 could induce apoptosis of U251 and A172 cells. Therefore, through bioinformatics methods and cell experiments, our study developed a new peroxisome-related gene signature that migh t help improve personalized OS prediction in LGG patients.
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Glioma , Peroxissomos , Humanos , Peroxissomos/genética , Glioma/genética , Domínio AAA , Adenosina Trifosfatases , Apoptose , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Carbohydrate antigen (CA) 19-9 and histological grade can serve as indicators of the biological characteristics of pancreatic ductal adenocarcinoma (PDAC). AIMS: The aim of this study was to investigate the combined impact of preoperative CA19-9 levels and histological grade on prognosis and classification accuracy in PDAC patients. METHODS AND RESULTS: A retrospective cohort study was conducted on 612 patients with PDAC who underwent curative pancreatectomy, and a biological risk model based on preoperative CA19-9 levels and histology grade was established. The prognostic importance of the biological risk model was evaluated, and its validity was confirmed through a validation cohort of 218 patients. The survival of patients with PDAC was independently associated with preoperative CA19-9 levels and histology grade, indicating a biological risk. This biological risk was incorporated into the eighth edition of the TNM staging system, leading to the development of a modified TNM (mTNM) staging system. Receiver operating characteristic (ROC) curves demonstrated that the mTNM staging system had a significantly larger area under the curve (AUC) than the TNM staging system. The discriminatory capacity of the mTNM staging system was further validated in an independent cohort. CONCLUSION: Biological risk based on preoperative CA19-9 and histological grade could predict the survival of patients with PDAC. The incorporation of biological risk into the TNM staging system has the potential to enhance the accuracy of patient classification in PDAC, predicting patient survival and enabling the development of individualized treatment plans.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/cirurgia , PrognósticoRESUMO
Aim: To compare the efficacy of arthroscopic debridement and olecranon fossa augmentation plasty in patients with elbow osteoarthritis. Methods: Eighty-four patients with elbow osteoarthritis admitted to our hospital were randomly divided into two groups with 42 cases in each group. Patients in the control group received expanded olecranon fossa plasty, while those in the observation group underwent arthroscopic debridement. Then the elbow joint function, VAS score, stress level, and incidence of complications were compared between the two groups. Results: The MEPS score, ROM level, and VAS score, as well as the expression of TNF-α, IL-6, and ACTH between the two groups, were significantly different before and after surgery (P < .05). Moreover, compared to patients in the control group, the MEPS score and ROM level of patients in the observation group were higher than those in the control group after six months since surgery, while VAS score, the levels of TNF-α, IL-6, and ACTH were lower on the second day after surgery (P < .05). Conclusion: Arthroscopic cleaning is more helpful in improving elbow joint function and alleviating pain in patients with osteoarthritis of the elbow compared to olecranon fossa augmentation and reconstruction surgery.
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Cotovelo , Osteoartrite , Humanos , Hormônio Adrenocorticotrópico , Artroscopia , Desbridamento , Úmero , Interleucina-6 , Osteoartrite/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfaRESUMO
Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.
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Infarto do Miocárdio , NAD , Camundongos , Animais , Nicotinamida Fosforribosiltransferase/genética , Arritmias Cardíacas/etiologia , Morte Súbita Cardíaca/etiologiaRESUMO
Presacral venous bleeding (PSVB) is an intractable situation during rectal mobilization. Till now, various methods for PSVB are introduced, but each of them has limitations. This article aims to introduce an effective approach for PSVB, which is created by Professor Xiaogang Bi. In the case of PSVB, a purse-string suture which highlighted each stitch penetrates periosteum of sacrum was performed around the bleeding site. After that, the branches of presacral venous plexus around the bleeding site were compressed to the sacrum when the stitches were tightened, the blood flow of the venous branches was blocked by the thread across them, the bleeding was controlled, and then, the knot was tied. From April 24th 2017 to November 6th 2022, ten patients who suffered PSVB during surgery accepted Bi's suture. With Bi's suture, all of the ten cases of PSVB were controlled effectively. Nine of ten cases were controlled immediately only by Bi's suture, one case which accompanied with blood oozing of sacrum wound was controlled by Bi's suture, bone wax, and pelvic gauze packing. Bi's suture is an effective approach for PSVB. It could be easily performed without the need of special materials.
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A ternary deep eutectic solvent (DES) consisting of choline chloride, lactic acid, and urea in a molar ratio of 1:2:2 was used to pretreat chamomile residue, followed by carbon dots (CDs) preparation using a one-pot solvothermal method. The CDs prepared under the suitable conditions had a high quantum yield of 47.34% and could be used as a bifunctional fluorescent probe for the detection of tartrazine and Fe(III). The concentration of tartrazine or Fe(III) had a good linear relationship with the fluorescence intensity of CDs that the determination coefficient (R2) was 0.9957 and 0.9943, and the limit of detection (LOD) was 40 nM and 119 nM, respectively. After verifying the different fluorescence quenching mechanisms of CDs by these two substances, a quantitative analysis was performed on real samples with recoveries of 90.70%â¼104.29%. Overall, this study provided a promising technology for chemical conversion from low-cost chamomile residue to attractive bifunctional fluorescent probe.
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Pontos Quânticos , Tartrazina , Tartrazina/análise , Compostos Férricos , Pontos Quânticos/química , Carbono/química , Corantes Fluorescentes/química , Camomila , Espectrometria de Fluorescência/métodosRESUMO
Possessing dual-targeted agents toward the lysosome and cancer cells, a ternary supramolecular assembly was constructed by a morpholine-modified permethyl ß-cyclodextrin, sulfonated porphyrin, and folic acid-modified chitosan via multivalent interactions. As compared with free porphyrin, the obtained ternary supramolecular assembly showed promoted photodynamic effect and achieved dual-targeted precise imaging in cancer cells.
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Antineoplásicos , Nanopartículas , Porfirinas , beta-Ciclodextrinas , Antineoplásicos/farmacologia , Porfirinas/farmacologia , Morfolinas/farmacologiaRESUMO
BACKGROUND: Percutaneous trigeminal rhizotomy (PTR) is a widely used procedure for trigeminal neuralgia. However, comprehensive analyses that combine anatomic, radiological, and surgical considerations are rare. OBJECTIVE: To present high-quality anatomic dissections and radiological studies that highlight the technical nuances of this procedure. METHODS: Six silicon-injected postmortem heads underwent PTR. The surgical corridors were dissected, and the neurovascular relationships were studied. In addition, 20 dried human skulls and 50 computed tomography angiography and MRI scans were collected to study the anatomic relationships for a customized puncture corridor. RESULTS: The PTR corridor was divided into 3 segments: the buccal segment (length, 34.76 ± 7.20 mm), the inferior temporal fossa segment (length, 42.06 ± 6.92 mm), and the Meckel cave segment (length, 24.75 ± 3.34 mm). The puncture sagittal (α) and axial (ß) angles measured in this study were 38.32° ± 4.62° and 19.13° ± 2.82°, respectively. The precondylar reference line coincided with the foramen ovale in 75% of the computed tomography angiography scans, and the postcondylar line coincided with the carotid canal in 70% of the computed tomography angiography scans; these lines serve as the intraoperative landmarks for PTR. The ovale-carotid-pterygoid triangle, delineated by drawing a line from the foramen ovale to the carotid canal and the lateral pterygoid plate, is a distinguished landmark to use for avoiding neurovascular injury during fluoroscopy. CONCLUSION: Knowledge of the anatomic and radiological features of PTR is essential for a successful surgery, and a customized technical flow is a safe and effective way to access the foramen ovale.
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Rizotomia , Neuralgia do Trigêmeo , Humanos , Rizotomia/métodos , Radiografia , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/cirurgia , Osso Esfenoide , CadáverRESUMO
Introduction: We aim to explore the association between chronic kidney disease (CKD) and cataracts. Methods: A total of 121,380 participants with adequate information collected from 29 community-based recruitment centers since 2008 were analyzed. The association between CKD and self-reported diagnosed cataracts was examined in a cross-sectional cohort and was validated in a longitudinal cohort of 25,263 participants without cataracts at baseline. Results and discussion: Of all participants, cataracts occurred in 503/1,947 (26%) and 10,464/119,433 (9%) subjects in the CKD and non-CKD groups, respectively. Multivariate logistic regression showed that CKD was significantly associated with a higher prevalence of self-reported diagnosed cataracts. In the validation cohort, a higher incidence of cataracts was also noted in the CKD group (65/317, 21%) compared to the non-CKD group (1,964/24,252, 8%) during a mean 47-month follow-up. After adjusting for confounders, subjects with CKD had a 1.498-fold higher risk of incident cataracts than those without CKD (95% confidence interval = 1.114 to 2.013, p value = 0.007). We found that CKD was associated with a higher prevalence of cataracts as well as incident cataracts, which suggests CKD patients and their primary physicians should be aware of this disease and can provide a clue for further exploration of the possible mechanisms and treatments.
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Catarata , Insuficiência Renal Crônica , Humanos , Estudos Longitudinais , Estudos Transversais , Fatores de Risco , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , Catarata/epidemiologiaRESUMO
Competition among exchange interactions is able to induce novel spin correlations on a bipartite lattice without geometrical frustration. A prototype example is the spiral spin liquid, which is a correlated paramagnetic state characterized by subdimensional degenerate propagation vectors. Here, using spectral graph theory, we show that spiral spin liquids on a bipartite lattice can be approximated by a further-neighbor model on the corresponding line-graph lattice that is nonbipartite, thus broadening the space of candidate materials that may support the spiral spin liquid phases. As illustrations, we examine neutron scattering experiments performed on two spinel compounds, ZnCr_{2}Se_{4} and CuInCr_{4}Se_{8}, to demonstrate the feasibility of this new approach and expose its possible limitations in experimental realizations.
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M-STAR is a next generation polarized neutron reflectometer with advanced capabilities. A new focusing guide concept is optimized for samples with dimensions down to a millimeter range. A proposed hybrid pulse-skipping chopper will enable experiments at constant geometry at one incident angle in a broad range of wavevector transfer Q up to 0.3 A-1 for specular, off-specular, and GISANS measurements. M-STAR will empower nanoscience and spintronics studies routinely on small samples (â¼2 × 2 mm2) and of atomic-scale thickness using versatile experimental conditions of magnetic and/or electric fields, light, and temperature applied in situ to novel complex device-like nanosystems with multiple buried interfaces. M-STAR will enable improved grazing incidence diffraction measurements, as a surface-sensitive depth-resolved probe of, e.g., the out-of-plane component of atomic magnetic moments in ferromagnetic, antiferromagnetic, and more complex structures as well as in-plane atomic-scale structures inaccessible with contemporary diffractometry and reflectometry. New horizons will be opened by the development of an option to probe near-surface dynamics with inelastic grazing incidence scattering in the time-of-flight mode. These novel options in combination with ideally matched parameters of the second target station will place M-STAR in the world's leading position for high resolution polarized reflectometry.
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We aimed to investigate the association between habitual tea consumption and the risk of developing cataracts in a large community-based cohort study. We prospectively collected volunteers from 29 recruitment centers that were ⧠55 years old with no history of cataracts at the beginning of the study. There were 12,080 participants with available information in our study and were divided into two groups according to habitual tea consumption; non-tea-drinking and tea-drinking groups. The mean age was 59 years. Compared to the non-tea-drinking group, the tea-drinking group had a significantly lower incidence of developing cataracts (15.5% vs 12.1%) during follow-up of 46 months. In multivariate Cox proportional hazards regression analysis, the relative risk (RR) of incident cataracts was lower in the tea-drinking group than the non-tea-drinking group (RR = 0.848; 95% confidence interval [CI] = 0.751 to 0.957). Participants with ⧠2 cups per day were associated with almost 16% reduction in the risk of developing cataracts compared with the non-tea-drinking group (RR = 0.844; 95% CI = 0.741 to 0.961). Our study suggests that habitual tea consumption can reduce the incidence of cataracts and raises the possibility that the tea content may slow the progression of cataracts.
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Catarata , Catarata/epidemiologia , Catarata/etiologia , Catarata/prevenção & controle , Estudos de Coortes , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Risco , Fatores de RiscoRESUMO
The advent of macrocycle-based supramolecular chemistry can offer powerful strategies for regulating vital bioactivities in living systems and bring about emerging technology in biomedical science. Herein, we construct a supra-biomacromolecular nanosystem involving microtubules, cell-permeable porphyrins, and antimitotic peptide-decorated permethyl-ß-cyclodextrins for promoting cell apoptosis in a cooperative manner. Through specific polypeptide-tubulin recognition, cyclodextrin moieties are capable of anchoring to the tubulin surface and providing abundant hydrophobic microenvironments to accommodate the photosensitive porphyrins. Consequently, spherical tubulin aggregates are formed, and reactive oxygen species can be efficiently generated via the host-guest complexation. The combined usage of complexation-promoted photodynamic efficacy and tubulin aggregation gives more serious cell apoptosis under light irradiation in vitro and in vivo. To be envisioned, this supramolecularly enhanced photodynamic performance together with controlled aggregation of natural biomacromolecules may be developed as an innovative approach to improve the therapeutic potency against many diseases.
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Antimitóticos , Ciclodextrinas , Neoplasias , Porfirinas , beta-Ciclodextrinas , Ciclodextrinas/química , Humanos , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Medicina de Precisão , Espécies Reativas de Oxigênio , Tubulina (Proteína) , Microambiente Tumoral , beta-Ciclodextrinas/químicaRESUMO
Highly efficient discrimination between cancer cells and normal cells is full of challenges for precise diagnosis. Herein, we report an effective in situ-activated phosphorescence energy transfer supramolecular assembly constructed by a bromophenyl pyridine derivative (BPPY), cucurbit[8]uril (CB[8]), and rhodamine B-grafted hyaluronic acid (HAR) through noncovalent interaction. As compared with BPPY, CB[8] encapsulated two BPPY molecules, resulting in a biaxial pseudorotaxane supramolecular assembly showing purely organic room-temperature phosphorescence induced by macrocyclic confinement, which when further co-assembled with HAR, formed a multivalent supramolecular assembly with phosphorescence energy transfer. Benefitting from the targeting of hyaluronic acid and the cyclolactam ring ON-OFF reaction of HAR, such supramolecular assembly with an open ring presents red delayed fluorescence through phosphorescence energy transfer in cancer cells, while the assembly showed only green phosphorescence in normal cells, realizing highly efficient discrimination between cancer and normal cells. This supramolecular assembly is responsive to the physiological environment and provides a supramolecular platform for precise diagnosis.