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1.
J Mol Cell Cardiol ; 195: 55-67, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089571

RESUMO

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.

2.
Anal Chem ; 96(5): 2264-2272, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38266388

RESUMO

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.


Assuntos
Boratos , Metabolismo dos Lipídeos , Hepatopatias , Piranos , Animais , Camundongos , Imagem Óptica/métodos , Corantes Fluorescentes , Lipídeos
3.
Small ; 20(13): e2309131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37967324

RESUMO

Sustainable long-lived room temperature phosphorescence (RTP) materials with color-tunable afterglows are attractive but rarely reported. Here, cellulose is reconstructed by directed redox to afford ample active hydroxyl groups and water-solubility; arylboronic acids with various π conjugations can be facilely anchored to reconstructed cellulose via click chemistry within 1 min in pure water, resulting in full-color tunable RTP cellulose. The rigid environment provided by the B─O covalent bonds and hydrogen bonds can stabilize the triplet excitons, thus the target cellulose displays outstanding RTP performances with the lifetime of 2.67 s, phosphorescence quantum yield of 9.37%, and absolute afterglow luminance of 348 mcd m-2. Furthermore, due to the formation of various emissive species, the smart RTP cellulose shows excitation- and time-dependent afterglows. Taking advantages of sustainability, ultralong lifetime, and full-color tunable afterglows, et al, the environmentally friendly RTP cellulose is successfully used for nontoxic afterglow inks, delay lighting, and afterglow display.

4.
Nat Methods ; 18(6): 688-693, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34059828

RESUMO

Understanding cellular organization demands the best possible spatial resolution in all three dimensions. In fluorescence microscopy, this is achieved by 4Pi nanoscopy methods that combine the concepts of using two opposing objectives for optimal diffraction-limited 3D resolution with switching fluorescent molecules between bright and dark states to break the diffraction limit. However, optical aberrations have limited these nanoscopes to thin samples and prevented their application in thick specimens. Here we have developed an improved iso-stimulated emission depletion nanoscope, which uses an advanced adaptive optics strategy to achieve sub-50-nm isotropic resolution of structures such as neuronal synapses and ring canals previously inaccessible in tissue. The adaptive optics scheme presented in this work is generally applicable to any microscope with a similar beam path geometry involving two opposing objectives to optimize resolution when imaging deep in aberrating specimens.


Assuntos
Microscopia de Fluorescência/métodos , Nanotecnologia/métodos , Óptica e Fotônica/métodos , Imageamento Tridimensional , Razão Sinal-Ruído
5.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535795

RESUMO

Whether risk genes of severe coronavirus disease 2019 (COVID-19) from genome-wide association study could play their regulatory roles by interacting with host genes that were interacted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins was worthy of exploration. In this study, we implemented a network-based approach by developing a user-friendly software Network Calculator (https://github.com/Haoxiang-Qi/Network-Calculator.git). By using Network Calculator, we identified a network composed of 13 risk genes and 28 SARS-CoV-2 interacted host genes that had the highest network proximity with each other, with a hub gene HNRNPK identified. Among these genes, 14 of them were identified to be differentially expressed in RNA-seq data from severe COVID-19 cases. Besides, by expression enrichment analysis in single-cell RNA-seq data, compared with mild COVID-19, these genes were significantly enriched in macrophage, T cell and epithelial cell for severe COVID-19. Meanwhile, 74 pathways were significantly enriched. Our analysis provided insights for the underlying genetic etiology of severe COVID-19 from the perspective of network biology.


Assuntos
COVID-19 , RNA-Seq , SARS-CoV-2 , Proteínas Virais , COVID-19/genética , COVID-19/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Gravidade do Paciente , Fatores de Risco , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
6.
J Transl Med ; 22(1): 6, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167440

RESUMO

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.


Assuntos
Neoplasias da Mama , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/patologia , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Ácidos Graxos , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
7.
Opt Express ; 32(1): 857-870, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175105

RESUMO

Charge migration initiated by the coherent superposition of several electronic states is a basic process in intense laser-matter interactions. Observing this process on its intrinsic timescale is one of the central goals of attosecond science. Here, using forward-scattering photoelectron holography we theoretically demonstrate a scheme to probe the charge migration in molecules. In our scheme, by solving the time-dependent Schrödinger equation, the photoelectron momentum distributions (PEMDs) for strong-field tunneling ionization of the molecule are obtained. For a superposition state, it is shown that an intriguing shift of the holographic interference appears in the PEMDs, when the molecule is aligned perpendicularly to the linearly polarized laser field. With the quantum-orbit analysis, we demonstrate that this shift of the interference fringes is caused by the time evolution of the non-stationary superposition state. By analyzing the dependence of the shift on the final parallel momentum of the electrons, the relative phase and the expansion coefficient ratio of the two electronic states involved in the superposition state are determined accurately. Our study provides an efficient method for probing the charge migration in molecules. It will facilitate the application of the forward-scattering photoelectron holography to survey the electronic dynamics in more complex molecules.

8.
Chemistry ; 30(45): e202401929, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-38818768

RESUMO

Direct structural modification of small-molecule fluorophores represents a straightforward and appealing strategy for accessing new fluorescent dyes with desired functionalities. We report herein a general and efficient visible-light-mediated method for the direct C-H functionalization of BODIPY, an important fluorescent chromophore, using readily accessible and bench-stable aryl and alkenylthianthrenium salts. This practical approach operates at room temperature with extraordinary site-selectivity, providing a step-economical means to construct various valuable aryl- and alkenyl-substituted BODIPY dyes. Remarkably, this protocol encompasses a broad substrate scope and excellent functional-group tolerance, and allows for the modular synthesis of sophisticated symmetrical and asymmetrical disubstituted BODIPYs by simply employing different combinations of thianthrenium salts. Moreover, the late-stage BODIPY modification of complex drug molecules further highlights the potential of this novel methodology in the synthesis of fluorophore-drug conjugates.

9.
Nano Lett ; 23(3): 1030-1035, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36715359

RESUMO

Advances in the development of aggregation-induced emission luminogens (AIEgens) depend on understanding how the molecular packing affects their luminescent properties and on making nanoparticles (NPs) with desired sizes. Although reported strategies have advanced the field, rational control of molecular packing and efficient fabrication of AIEgen NPs sub-5.5 nm in diameter remain pressing issues. Here we report a "freeze assembly" strategy, in which the diameter of AIEgen NPs can be precisely tuned from ∼3 nm to hundreds of nanometers, and a molecular packing in kinetically trapped states that are not easily captured by conventional assembly methods can be obtained, leading to tunable fluorescence emissions. Therefore, this study provides a significant tool to fabricate organic luminescent nanomaterials with diameters smaller than 5 nm, which is of critical importance for biomedical applications; meanwhile, tuning molecular packing in nanoparticles displaying different fluorescence may help to shed new light on the mechanism of AIEgens.

10.
Molecules ; 29(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39064980

RESUMO

A new hydrazone Schiff base bridging ligand (H2LSchiff (E)-N'-((1-hydroxynaphthalen-2-yl)methylene)pyrazine-2-carbohydrazide) and L/D-proline were used to construct a pair of homochiral Dy6 cluster complexes, [Dy6(CO3)(L-Pro)6(LSchiff)4(HLSchiff)2]·5DMA·2H2O (L-1, L-HPro = L-proline; DMA = N,N-dimethylacetamide) and [Dy6(CO3)(D-Pro)6(LSchiff)4(HLSchiff)2]·5DMA·2H2O (D-1, D-HPro = D-proline), which show a novel triangular Dy6 topology. Notably, the fixation of CO2 in the air formed a carbonato central bridge, playing a key role in assembling L-1/D-1. Magnetic measurements revealed that L-1/D-1 displays intramolecular ferromagnetic coupling and magnetic relaxation behaviours. Furthermore, L-1/D-1 shows a distinct magneto-optical Faraday effect and has a second harmonic generation (SHG) response (1.0 × KDP) at room temperature. The results show that the immobilization of CO2 provides a novel pathway for homochiral multifunctional 4f cluster complexes.

11.
Molecules ; 29(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38893469

RESUMO

Hepatocellular carcinoma (HCC) results in the abnormal regulation of cellular metabolic pathways. Constraint-based modeling approaches can be utilized to dissect metabolic reprogramming, enabling the identification of biomarkers and anticancer targets for diagnosis and treatment. In this study, two genome-scale metabolic models (GSMMs) were reconstructed by employing RNA sequencing expression patterns of hepatocellular carcinoma (HCC) and their healthy counterparts. An anticancer target discovery (ACTD) framework was integrated with the two models to identify HCC targets for anticancer treatment. The ACTD framework encompassed four fuzzy objectives to assess both the suppression of cancer cell growth and the minimization of side effects during treatment. The composition of a nutrient may significantly affect target identification. Within the ACTD framework, ten distinct nutrient media were utilized to assess nutrient uptake for identifying potential anticancer enzymes. The findings revealed the successful identification of target enzymes within the cholesterol biosynthetic pathway using a cholesterol-free cell culture medium. Conversely, target enzymes in the cholesterol biosynthetic pathway were not identified when the nutrient uptake included a cholesterol component. Moreover, the enzymes PGS1 and CRL1 were detected in all ten nutrient media. Additionally, the ACTD framework comprises dual-group representations of target combinations, pairing a single-target enzyme with an additional nutrient uptake reaction. Additionally, the enzymes PGS1 and CRL1 were identified across the ten-nutrient media. Furthermore, the ACTD framework encompasses two-group representations of target combinations involving the pairing of a single-target enzyme with an additional nutrient uptake reaction. Computational analysis unveiled that cell viability for all dual-target combinations exceeded that of their respective single-target enzymes. Consequently, integrating a target enzyme while adjusting an additional exchange reaction could efficiently mitigate cell proliferation rates and ATP production in the treated cancer cells. Nevertheless, most dual-target combinations led to lower side effects in contrast to their single-target counterparts. Additionally, differential expression of metabolites between cancer cells and their healthy counterparts were assessed via parsimonious flux variability analysis employing the GSMMs to pinpoint potential biomarkers. The variabilities of the fluxes and metabolite flow rates in cancer and healthy cells were classified into seven categories. Accordingly, two secretions and thirteen uptakes (including eight essential amino acids and two conditionally essential amino acids) were identified as potential biomarkers. The findings of this study indicated that cancer cells exhibit a higher uptake of amino acids compared with their healthy counterparts.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Humanos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Modelos Biológicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos/farmacologia , Redes e Vias Metabólicas , Proliferação de Células/efeitos dos fármacos
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 193-203, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38686715

RESUMO

Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.


Assuntos
População Rural , População Urbana , Humanos , Idoso , China , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Serviços de Saúde para Idosos/estatística & dados numéricos , Idoso de 80 Anos ou mais , Necessidades e Demandas de Serviços de Saúde
13.
Lab Invest ; 103(12): 100260, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37839635

RESUMO

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancer worldwide, has an exceedingly poor prognosis. Tandem C2 domain nuclear protein (TC2N) has been implicated in tumorigenesis and serves as an oncogene or tumor suppressor in different types of cancer. Here, we explore the possible regulatory activities and molecular mechanisms of TC2N in HCC progression. However, TC2N expression was significantly upregulated in HCC tissues and hepatoma cell lines, and this upregulation was positively correlated with tumor progression in HCC patients. The ectopic overexpression of TC2N accelerated the proliferation, migration, and invasion of HCC cells, whereas its knockdown showed the opposite effects. Bioinformatics analysis showed that TC2N participates in the regulation of the Wnt/ß-catenin signaling pathway. Mechanistically, TC2N activated the Wnt/ß-catenin signaling pathway by regulating the expression levels of ß-catenin and its downstream targets CyclinD1, MMP7, c-Myc, c-Jun, AXIN2, and glutamine synthase. Furthermore, the deletion of ß-catenin effectively neutralized the regulation of TC2N in HCC proliferation and metastasis. Overall, this study showed that TC2N promotes HCC proliferation and metastasis by activating the Wnt/ß-catenin signaling pathway, indicating that TC2N might be a potential molecular target for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , beta Catenina/metabolismo , Via de Sinalização Wnt/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
14.
Anal Chem ; 95(39): 14616-14623, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37725051

RESUMO

Cell spheroids offer alternative in vitro cell models to monolayer cultured cells because they express complexities similar to those of in vivo tissues, such as cellular responses to drugs and chemicals. Raman spectroscopy emerged as a powerful analytical tool for detecting chemical changes in living cells because it nondestructively provides vibrational information regarding a target. Although multiple iterations are required in drug screening to determine drugs to treat cell spheroids and assess the inter-spheroid heterogeneity, current Raman applications used in spheroids analysis allow the observation of only a few spheroids owing to the low throughput of Raman spectroscopy. In this study, we developed a multifocal Raman spectrophotometer that enables simultaneous analysis of multiple spheroids in separate wells of a regular 96-well plate. By utilizing 96 focal spots excitation and parallel signal collection, our system can improve the throughput by approximately 2 orders of magnitude compared to a conventional single-focus Raman microscope. The Raman spectra of HeLa cell spheroids treated with anticancer drugs and HepG2 cell spheroids treated with free fatty acids were measured simultaneously, and concentration-dependent cellular responses were observed in both studies. Using the multifocal Raman spectrophotometer, we rapidly observed chemical changes in spheroids, and thus, this system can facilitate the application of Raman spectroscopy in analyzing the cellular responses of spheroids.

15.
Opt Lett ; 48(7): 1726-1729, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221751

RESUMO

Precise control of irradiance distribution is a complicated problem for freeform lens design, especially when the target is non-uniform. Realistic sources are often simplified as zero-etendue ones in cases designed for content-rich irradiance fields while the surfaces are usually assumed smooth everywhere. These practices can limit the performance of the designs. We developed an efficient proxy for Monte Carlo (MC) ray tracing under extended sources, with the linear property of our triangle mesh (TM) freeform surface. Our designs show finer irradiance control compared to their counterparts from the LightTools design feature. One of the lenses is fabricated and evaluated in an experiment, and performed as expected.

16.
Opt Lett ; 48(10): 2535-2538, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37186701

RESUMO

Structured illumination microscopy (SIM) allows non-invasive visualization of nanoscale subcellular structures. However, image acquisition and reconstruction become the bottleneck to further improve the imaging speed. Here, we propose a method to accelerate SIM imaging by combining the spatial re-modulation principle with Fourier domain filtering and using measured illumination patterns. This approach enables high-speed, high-quality imaging of dense subcellular structures using a conventional nine-frame SIM modality without phase estimation of the patterns. In addition, seven-frame SIM reconstruction and additional hardware acceleration further improve the imaging speed using our method. Furthermore, our method is also applicable to other spatially uncorrelated illumination patterns, such as distorted sinusoidal, multifocal, and speckle patterns.

17.
Opt Lett ; 48(21): 5547-5550, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910699

RESUMO

Fluorescence lifetime microscopy has been widely used in quantifying cellular interaction or histopathological identification of different stained tissues. A novel, to the best of our knowledge, approach for high-throughput multiplexed fluorescence lifetime imaging is presented. To establish a high-throughput fluorescence lifetime acquisition system, a uniformed illumination optical focus array was generated by a novel computer-generated hologram algorithm based on matrix triple product. This, in conjunction with an array detector and multichannel time-correlated single-photon counting, enables the full use of the acquisition ability of each detector. By utilizing interval segmentation of photon time detection, a high-throughput multiplexed fluorescence lifetime imaging is achieved. Experimental results demonstrate that this method achieves a fivefold increase in the collection throughput of fluorescence lifetime and is capable of simultaneous dual-target fluorescence lifetime measurement.

18.
Bipolar Disord ; 25(5): 410-421, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36633396

RESUMO

OBJECTIVE: Due to the phenotypic heterogeneity and etiological complexity of bipolar disorder (BD), many patients do not respond well to the current medications, and developing novel effective treatment is necessary. Whether any BD genome-wide association study (GWAS) risk genes were targets of existing drugs or novel drugs that can be repurposed in the clinical treatment of BD is a hot topic in the GWAS era of BD. METHODS: A list of 425 protein-coding BD risk genes was distilled through the BD GWAS, and 4479 protein-coding druggable targets were retrieved from the druggable genome. The overlapped genes/targets were subjected to further analyses in DrugBank, Pharos, and DGIdb datasets in terms of their FDA status, mechanism of action and primary indication, to identify their potential for repurposing. RESULTS: We identified 58 BD GWAS risk genes grouped as the druggable targets, and several genes were given higher priority. These BD risk genes were targets of antipsychotics, antidepressants, antiepileptics, calcium channel antagonists, as well as anxiolytics and analgesics, either existing clinically-approved drugs for BD or the drugs than can be repurposed for treatment of BD in the future. Those genes were also likely relevant to BD pathophysiology, as many of them encode ion channel, ion transporter or neurotransmitter receptor, or the mice manipulating those genes are likely to mimic the phenotypes manifest in BD patients. CONCLUSIONS: This study identifies several targets that may facilitate the discovery of novel treatments in BD, and implies the value of conducting GWAS into clinical translation.


Assuntos
Transtorno Bipolar , Humanos , Animais , Camundongos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Antidepressivos , Fenótipo
19.
Inorg Chem ; 62(49): 20184-20193, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37994798

RESUMO

Two pairs of homochiral Dy(III) tetranuclear cluster complexes derived from (+)/(-)-3-trifluoroacetyl camphor (D-Htfc/L-Htfc), [Dy4(OH)2(L1)4(D-tfc)2(DMF)2]·4DMF (D-1) [H2L1 = (E)-2-(2-hydroxy-3-methoxybenzylideneamino)phenol)]/[Dy4(OH)2(L1)4(L-tfc)2(DMF)2]·4DMF (L-1) and [Dy4(OH)2(L2)4(D-tfc)2(DMF)2]·2H2O·3MeCN (D-2) [H2L2 = (E)-3-(2-hydroxy-3-methoxybenzylideneamino)naphthalen-2-ol]/[Dy4(OH)2(L2)4(L-tfc)2(DMF)2]·2H2O·3MeCN (L-2), were synthesized at room temperature, which have a Dy4 parallelogram-like core. The magnetic studies revealed that D-1 exhibits single-molecule magnet (SMM) behavior under zero dc magnetic field, and its magnetic relaxation has a distinct Raman process in addition to the Orbach process, with the Ueff/k value of 57.5 K and the C value of 28.27 s-1K-2.14; while D-2 displays dual magnetic relaxation behavior at 0 Oe field, with the Ueff/k value 114.8 K for the slow relaxation process (SR) and the C value of 10.656 s-1K-5.80 for the fast relaxation process (FR), respectively. Theoretical calculations indicated that the conjugated groups (phenyl vs naphthyl) of the Schiff base bridging ligands (H2L1 and H2L2) significantly affect the intramolecular magnetic interactions between the Dy3+ ions and ultimately lead to different relaxations. Furthermore, magnetic circular dichroism (MCD) measurements showed that these two pairs of Dy4 enantiomers exhibit strong room temperature magneto-optical Faraday effects; notably, increasing the conjugated group on the Schiff base bridging ligand is beneficial to enhancing the magneto-optical Faraday effects.

20.
J Gastroenterol Hepatol ; 38(9): 1576-1586, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37403251

RESUMO

BACKGROUND AND AIM: Worldwide, colorectal cancer (CRC) is the third most common cancer and ranks second among the leading causes of cancer death. This study aims to devise and validate a scoring system based on metabolic parameters to predict the risk of advanced colorectal neoplasia (ACN) in a large Chinese population. METHODS: This was a cohort study of 495 584 symptomatic subjects aged 40 years or older who have received colonoscopy in Hong Kong from 1997 to 2017. The algorithm's discriminatory ability was evaluated as the area under the curve (AUC) of the mathematically constructed receiver operating characteristic curve. RESULTS: Age, male gender, inpatient setting, abnormal aspartate transaminase/alanine transaminase, white blood cell, plasma gamma-glutamyl transferase, high-density lipoprotein cholesterol, triglycerides, and hemoglobin A1c were significantly associated with ACN. A scoring of < 2.65 was designated as "low risk (LR)." Scores at 2.65 or above had prevalence higher than the overall prevalence and hence were assigned as "high risk (HR)." The prevalence of ACN was 32% and 11%, respectively, for HR and LR groups. The AUC for the risk score in the derivation and validation cohort was 70.12%. CONCLUSIONS: This study has validated a simple, accurate, and easy-to-use scoring algorithm, which has a high discriminatory capability to predict ACN in symptomatic patients. Future studies should examine its predictive performance in other population groups.


Assuntos
Neoplasias Colorretais , Humanos , Masculino , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Fatores de Risco , Previsões , Colonoscopia/efeitos adversos , Detecção Precoce de Câncer , Pacientes Internados
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