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1.
J Transl Med ; 21(1): 278, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098551

RESUMO

BACKGROUND: Nonkeratinizing nasopharyngeal carcinoma (NK-NPC) has a strong association with Epstein-Barr virus (EBV) infection. The role of NK cells and the tumor cell evolutionary trajectory in NK-NPC remain unclear. In this study, we aim to investigate the function of NK cell and the evolutionary trajectory of tumor cells in NK-NPC by single-cell transcriptomic analysis, proteomics and immunohistochemistry. METHODS: NK-NPC (n = 3) and normal nasopharyngeal mucosa cases (n = 3) were collected for proteomic analysis. Single-cell transcriptomic data of NK-NPC (n = 10) and nasopharyngeal lymphatic hyperplasia (NLH, n = 3) were obtained from Gene Expression Omnibus (GSE162025 and GSE150825). Quality control, dimension reduction and clustering were based on Seurat software (v4.0.2) process and batch effects were removed by harmony (v0.1.1) software. Normal cells of nasopharyngeal mucosa and tumor cells of NK-NPC were identified using copykat software (v1.0.8). Cell-cell interactions were explored using CellChat software (v1.4.0). Tumor cell evolutionary trajectory analysis was performed using SCORPIUS software (v1.0.8). Protein and gene function enrichment analyses were performed using clusterProfiler software (v4.2.2). RESULTS: A total of 161 differentially expressed proteins were obtained between NK-NPC (n = 3) and normal nasopharyngeal mucosa (n = 3) by proteomics (log2 fold change > 0.5 and P value < 0.05). Most of proteins associated with the nature killer cell mediated cytotoxicity pathway were downregulated in the NK-NPC group. In single cell transcriptomics, we identified three NK cell subsets (NK1-3), among which NK cell exhaustion was identified in the NK3 subset with high ZNF683 expression (a signature of tissue-resident NK cell) in NK-NPC. We demonstrated the presence of this ZNF683 + NK cell subset in NK-NPC but not in NLH. We also performed immunohistochemical experiments with TIGIT and LAG3 to confirm NK cell exhaustion in NK-NPC. Moreover, the trajectory analysis revealed that the evolutionary trajectory of NK-NPC tumor cells was associated with the status of EBV infection (active or latent). The analysis of cell-cell interactions uncovered a complex network of cellular interactions in NK-NPC. CONCLUSIONS: This study revealed that the NK cell exhaustion might be induced by upregulation of inhibitory receptors on the surface of NK cells in NK-NPC. Treatments for the reversal of NK cell exhaustion may be a promising strategy for NK-NPC. Meanwhile, we identified a unique evolutionary trajectory of tumor cells with active status of EBV-infection in NK-NPC for the first time. Our study may provide new immunotherapeutic targets and new sight of evolutionary trajectory involving tumor genesis, development and metastasis in NK-NPC.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Nasofaríngeas/genética , Transcriptoma/genética , Proteômica , Herpesvirus Humano 4/fisiologia , Células Matadoras Naturais/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço
2.
Opt Express ; 31(10): 15682-15696, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157663

RESUMO

Mueller matrix microscopy is capable of polarization characterization of pathological samples and polarization imaging based digital pathology. In recent years, hospitals are replacing glass coverslips with plastic coverslips for automatic preparations of dry and clean pathological slides with less slide-sticking and air bubbles. However, plastic coverslips are usually birefringent and introduce polarization artifacts in Mueller matrix imaging. In this study, a spatial frequency based calibration method (SFCM) is used to remove such polarization artifacts. The polarization information of the plastic coverslips and the pathological tissues are separated by the spatial frequency analysis, then the Mueller matrix images of pathological tissues are restored by matrix inversions. By cutting two adjacent lung cancer tissue slides, we prepare paired samples of very similar pathological structures but one with a glass coverslip and the other with a plastic coverslip. Comparisons between Mueller matrix images of the paired samples show that SFCM can effectively remove the artifacts due to plastic coverslip.


Assuntos
Microscopia , Birrefringência , Calibragem
3.
Inorg Chem ; 62(17): 6560-6564, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37083359

RESUMO

Herein, a deuteration strategy is proposed to enhance the photoluminescence quantum yield (PLQY) of a Dy(III) complex. The perdeuterated Dy(III) complex Dy(D-DPPOP)3 (D-DPPOP = 6-[bis(phenyl-d5)phosphoryl]picolinate-d3) exhibits a high PLQY of up to 72% in deuterated chloroform, which is 4.8 times higher than that of the nondeuterated Dy(III) complex Dy(DPPOP)3. Then the corresponding ultraviolet-excited light-emitting diode is fabricated, showing a warm-white light with a Commission Internationale de l'Eclairage (CIE) of (0.36, 0.41) and a color temperature of around 4800 K. The deuteration strategy to improve the PLQY of the Dy(III) complex is proved in this work, and it will inspire the further design of white-emission Dy(III) complexes with high efficiency.

4.
Rheumatol Int ; 43(6): 1183-1193, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36912940

RESUMO

IgG4-related disease (IgG4-RD), a rare immune-mediated chronic fibro-inflammatory condition, has various initial symptoms, thus posing diagnostic and therapeutic challenges. Here, we report a case of IgG4-RD in a 35-year-old man with initial clinical symptoms of facial edema and recent onset of proteinuria. It took more than 1 year from the onset of clinical symptoms to diagnosis. Pathological examination of renal biopsy revealed significant renal interstitial lymphoid tissue hyperplasia simulating growth pattern of lymphoma. Immunohistochemical (IHC) staining results showed that CD4 + T lymphocyte hyperplasia was dominant. There was no significant deletion of CD2/CD3/CD5/CD7. No monoclone was detected in TCR gene rearrangement. IHC staining showed that the number of IgG4-positive cells was greater than 100/HPF. The ratio of IgG4/IgG was greater than 40%. Combined with clinically examinations, IgG4-related tubulointerstitial nephritis was considered. Further cervical lymph node biopsy results suggested IgG4-related lymphadenopathy. He received methylprednisolone 40 mg/day intravenously for 10 days, leading to normal results of laboratory tests and clinical manifestations. The patient had a good prognosis without recurrence during 14 months of follow-up. This case report can be used as a reference for early diagnosis and treatment of such patients in the future.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Linfadenopatia , Nefrite Intersticial , Masculino , Humanos , Adulto , Doença Relacionada a Imunoglobulina G4/patologia , Hiperplasia/patologia , Rim/patologia , Nefrite Intersticial/diagnóstico , Linfonodos/patologia , Linfadenopatia/patologia , Imunoglobulina G/uso terapêutico
5.
Int Arch Occup Environ Health ; 96(1): 179-190, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35989361

RESUMO

PURPOSE: Occupational harmful factors, such as shift work, are attracting increasing attention as a potential cause of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to identify the association between shift work and NAFLD incidence in Chinese rail population. METHODS: A cohort study was conducted among 14,112 rail workers for 4-year follow-up. Shift work frequency and other potential variables were recorded by questionnaires, including demographic, lifestyle, and occupation information. Besides, body mass index, blood pressure, fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase were measured by anthropometric measurement and blood test. Diagnosis of new NAFLD case was based on abdominal ultrasonography. Cox proportional hazards regression model was used to determine whether shift work has effect on occurrence of NAFLD. RESULTS: The incidence of NAFLD was 30.43% in total subjects. After adjustment for possible confounders, the RRs of NAFLD were 1.069 (95% CI 0.998-1.146) and 1.179 (95% CI 1.059-1.312) in occasionally shift work group and frequently shift work group respectively, compared to the seldom shift work group. In stratified analyses, the RRs of NAFLD incidence linked to shift work exposure seems increase among female and elder. The results of three sensitivity analyses were similar with main analysis. CONCLUSIONS: This research provided further evidence of positive harmful effect of shift work on NAFLD incidence in Chinese rail workers, particularly in frequently shift work population. The risk estimate of shift work on NAFLD was higher in female and elder.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Jornada de Trabalho em Turnos , Humanos , Feminino , Idoso , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos de Coortes , Estudos Longitudinais , Incidência , População do Leste Asiático , Fatores de Risco
6.
Angew Chem Int Ed Engl ; 62(15): e202300224, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36757154

RESUMO

Photocatalytic hydrogen (H2 ) evolution represents a promising and sustainable technology. Covalent organic frameworks (COFs)-based photocatalysts have received growing attention. A 2D fully conjugated ethylene-linked COF (BTT-BPy-COF) was fabricated with a dedicated designed active site. The introduced bipyridine sites enable a facile post-protonation strategy to fine-tune the actives sites, which results in a largely improved charge-separation efficiency and increased hydrophilicity in the pore channels synergically. After modulating the degree of protonation, the optimal BTT-BPy-PCOF exhibits a remarkable H2 evolution rate of 15.8 mmol g-1 h-1 under visible light, which surpasses the biphenyl-based COF 6 times. By using different types of acids, the post-protonation is proved to be a potential universal strategy for promoting photocatalytic H2 evolution. This strategy would provide important guidance for the design of highly efficient organic semiconductor photocatalysts.

7.
Angew Chem Int Ed Engl ; 62(24): e202302192, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37020235

RESUMO

Doublet emission from open-shell molecules has demonstrated its research and application value in recent years. However, understandings of the photoluminescence mechanism of open-shell molecules are far less than that of closed-shell molecules, leading to challenges in molecular design of efficient doublet emission systems. Here we report a cerium(III) 4-(9H-carbozol-9-yl)phenyl-tris(pyrazolyl)borate complex Ce(CzPhTp)3 with a new luminescence mechanism of delayed doublet emission, which also represents the first example with metal-centered delayed photoluminescence. The energy gap between the doublet and triplet excited states of Ce(CzPhTp)3 is reduced by the management of the inner and outer coordination spheres, thereby promoting efficient energy transfer between the two excited states and activating the delayed emission. The photoluminescence mechanism discovered may provide a new way for the design of efficient doublet emission and bring insights into rational molecular design and energy level regulation in open-shell molecules.

8.
Environ Res ; 215(Pt 1): 114251, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36063911

RESUMO

Evidence on the associations of prolonged ambient pollutants exposure with chronic non-communicable diseases among middle-aged and elderly residents is still limited. This prospective cohort study intends to investigate the long-term effects of ambient pollution on hypertension and diabetes incidence among relatively older residents in China. Individual particulate matter exposure levels were estimated by satellite-based model. Individual gaseous pollutants exposure levels were estimated by Inverse Distance Weighted model. A Cox regression model was employed to assess the risks of hypertension and diabetes morbidity linked to air pollutants exposures. The cross-product term of ambient pollutants exposure and covariates was further added into the regression model to test whether covariates would modify these air pollution-morbidity associations. During the period from 2014 to 2018, a total of 97,982 subjects completed follow-up. 12,371 incidents of hypertension and 2034 of diabetes occurred. In the multi-covariates model, the hazard ratios (HR) and 95% confidence interval (CI) were 1.49 (1.45-1.52), 1.28 (1.26-1.30), 1.17 (1.15-1.18), 1.21 (1.17-1.25) and 1.33 (1.31-1.35) for hypertension morbidity per 10 µg/m3 increment in PM1, PM2.5, PM10, NO2 and SO2, respectively. For diabetes onsets, the HR (95% CI) were 1.17 (1.11-1.23), 1.09 (1.04-1.13), 1.06 (1.02-1.09), 1.02 (0.95-1.10), and 1.24 (1.19-1.29), respectively. In addition, for hypertension analyses, the effect estimates were more pronounced in the participants with age <60 years old, BMI ≥24 kg/m2, and frequent alcohol drinking. These findings provided the evidence on elevated risks of morbidity of hypertension and diabetes associated with prolonged ambient pollutants exposure at relatively high levels.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hipertensão , Doenças não Transmissíveis , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Estudos de Coortes , Exposição Ambiental/análise , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Doenças não Transmissíveis/epidemiologia , Material Particulado/análise , Material Particulado/toxicidade , Estudos Prospectivos
9.
J Chem Phys ; 157(13): 134104, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36209000

RESUMO

Quantum simulation of chemical Hamiltonians enables the efficient calculation of chemical properties. Mapping is one of the essential steps in simulating fermionic systems on quantum computers. In this work, a unified framework of transformations mapping fermionic systems to qubit systems is presented and many existing transformations-such as Jordan-Wigner, Bravyi-Kitaev, and parity transformations-are included in this framework. Based on this framework, the Multilayer Segmented Parity (MSP) transformation is proposed. The MSP transformation is a general mapping with an adjustable parameter vector, which can be viewed as a generalization of the above-mentioned mappings. Furthermore, the MSP transformation can adjust flexibly when dealing with different systems. Applying these mappings to the electronic structure Hamiltonians of various molecules, the MSP transformation is found to perform better on a number of Pauli operators and gates needed in the circuit of Hamiltonian simulation. The MSP transformation will reduce the qubit gate requirement for Hamiltonian simulation on noisy intermediate-scale quantum devices, and it will provide a much wider choice of mappings for researchers.

10.
Entropy (Basel) ; 24(11)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36421493

RESUMO

When the Dempster-Shafer evidence theory is applied to the field of information fusion, how to reasonably transform the basic probability assignment (BPA) into probability to improve decision-making efficiency has been a key challenge. To address this challenge, this paper proposes an efficient probability transformation method based on neural network to achieve the transformation from the BPA to the probabilistic decision. First, a neural network is constructed based on the BPA of propositions in the mass function. Next, the average information content and the interval information content are used to quantify the information contained in each proposition subset and combined to construct the weighting function with parameter r. Then, the BPA of the input layer and the bias units are allocated to the proposition subset in each hidden layer according to the weight factors until the probability of each single-element proposition with the variable is output. Finally, the parameter r and the optimal transform results are obtained under the premise of maximizing the probabilistic information content. The proposed method satisfies the consistency of the upper and lower boundaries of each proposition. Extensive examples and a practical application show that, compared with the other methods, the proposed method not only has higher applicability, but also has lower uncertainty regarding the transformation result information.

11.
Allergol Immunopathol (Madr) ; 49(6): 16-30, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761652

RESUMO

BACKGROUND AND OBJECTIVE: Guizhi Jia Shaoyao decoction (GSD) is widely used in the clinical treatment of knee osteoarthritis (KOA). However, the underlying molecular mechanisms remain unclear. The aim of this study was to explore functional mechanisms of GSD in treating KOA by utilizing network pharmacology-based approaches. METHODS: Candidate components and targets of GSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. NCBI, Genecards, Drugbank, and Therapeutic Target Database (TTD) were used to establish a target database for KOA. Then, an interactive network diagram of "drugs-active components-targets" was plotted with Cytoscape open source bioinformatics software. A protein-protein interaction network was constructed and related protein interaction relationships were analyzed based on the STRING database. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analysis were conducted based on intersected targets. Molecular docking provided an assessment tool for verifying binding of components and targets. It was performed by AutoDock molecular modeling simulation software. RESULTS: In all, 103 active components were successfully identified, and corresponding 133 targets were searched for treating KOA. Functional enrichment analysis suggested that GSD exerts its pharmacological effect in treating KOA by regulating multiple pathways, such as PI3K-Akt, tumor necrosis factor, Toll-like receptor (TLR), and nuclear factor kappa B signaling pathways. Molecular docking analysis depicted that representative components bound firmly to key targets. CONCLUSION: This study revealed the synergistic effects of multiple components, targets, and pathways of GSD for treating KOA. This would enhance the understanding of potential molecular mechanisms of GSD for treating KOA and lay a foundation for further experimental research.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
13.
Chemphyschem ; 18(11): 1466-1469, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-27223875

RESUMO

Inspired by marine mussel adhesive systems, numerous 3,4-dihydroxyphenylalanine (DOPA)-containing surface coating materials have been recently designed. It is well known that DOPA has a strong adhesion ability to different kinds of wet surfaces. However, the molecular mechanism of DOPA adhesion remains elusive. Recent biophysical studies of DOPA adhesion by both surface force apparatus (SFA) and atomic force microscopy (AFM) suggest that DOPA can bind to a wide range of surfaces exhibiting diverse chemical properties through different binding mechanisms. Here, using AFM-based single-molecule force spectroscopy, we show that even for chemically well-defined crystal surfaces, DOPA can bind to them by multiple binding modes. The binding forces between DOPA and different rutile TiO2 surfaces can vary within a broad range from 40-800 pN at a pulling speed of 1000 nm s-1 and are largely dependent on the surface properties. Our findings indicate that the local chemical environment can greatly affect DOPA adhesion, and that single-molecule force spectroscopy is a unique tool to reveal the heterogeneity of DOPA adhesion to the same surface.


Assuntos
Di-Hidroxifenilalanina/química , Titânio/química , Sítios de Ligação , Microscopia de Força Atômica , Propriedades de Superfície
14.
Appl Microbiol Biotechnol ; 101(17): 6697-6703, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28710557

RESUMO

α-Toxin, one of the best known pore-forming proteins produced by Staphylococcus aureus (S. aureus), is a critical virulence factor in multiple infections. The necessity of α-toxin for S. aureus pathogenicity suggests that this toxin is an important target for the development of a potential treatment strategy. In this study, we showed that lysionotin, a natural compound, can inhibit the hemolytic activity of culture supernatants by S. aureus by reducing α-toxin expression. Using real-time PCR analysis, we showed that transcription of hla (the gene encoding α-toxin) and agr (the locus regulating hla) was significantly inhibited by lysionotin. Lactate dehydrogenase and live/dead assays indicated that lysionotin effectively protected human alveolar epithelial cells against S. aureus, and in vivo studies also demonstrated that lysionotin can protect mice from pneumonia caused by S. aureus. These findings suggest that lysionotin is an efficient inhibitor of α-toxin expression and shows significant protection against S. aureus in vitro and in vivo. This study supports a potential strategy for the treatment of S. aureus infection by inhibiting the expression of virulence factors and indicates that lysionotin may be a potential treatment for S. aureus pneumonia.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/genética , Flavonoides/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Animais , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Proteínas Hemolisinas/efeitos dos fármacos , Proteínas Hemolisinas/genética , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Reação em Cadeia da Polimerase em Tempo Real , Staphylococcus aureus/genética , Transativadores/efeitos dos fármacos , Transativadores/genética , Fatores de Virulência/genética
15.
J Transl Med ; 14: 79, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-27004414

RESUMO

BACKGROUND: To explore whether plasma fatty acids and SNPs in the fatty acid desaturase (FADS) gene associated with type 2 diabetes (T2D) and coronary artery disease (CAD). METHODS: In this cross-sectional study, we utilized gas chromatography-mass spectrometric analysis and the high-resolution melting method to detect plasma fatty acids and SNPs respectively (rs174537G>T, rs174616C>T, rs174460T>C, and rs174450A>C) in 234 T2D, 200 CAD, 185 T2D&CAD patients, and 253 healthy controls. RESULTS: We found that T2D&CAD patients had the highest plasma arachidonic acid, dihomo-gamma-linolenic acid and delta-6 desaturase, and the lowest stearic acid, linolenic acid, and saturated fatty acids; plasma eicosapentaenoic acid and docosahexaenoic acid elevated in T2D patients, but significantly reduced in CAD patients. Moreover, T2D patients with rs174537 GG genotype were at risk of developing T2D&CAD (odds ratio (OR) 1.763; 95 % CI 1.143-2.718; p = 0.010), with elevated plasma LDL-cholesterol, arachidonic acid, and delta-6 desaturase. CONCLUSIONS: Our results show that SNPs in FADS gene (particularly rs174537) associate with plasma fatty acids and desaturase levels in patients with both T2D and CAD, which maybe increases the risk of CAD in diabetic patients.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos/sangue , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Doença da Artéria Coronariana/complicações , Dessaturase de Ácido Graxo Delta-5 , Diabetes Mellitus Tipo 2/complicações , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Fatores de Risco
16.
Front Plant Sci ; 15: 1413595, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974979

RESUMO

In response to the issue of harvesting machine failures affecting crop harvesting timing, this study develops an emergency scheduling model and proposes a hybrid optimization algorithm that combines a genetic algorithm and an ant colony algorithm. By enhancing the genetic algorithm's crossover and mutation methods and incorporating the ant colony algorithm, the proposed algorithm can prevent local optima, thus minimizing disruptions to the overall scheduling plan. Field data from Deyang, Sichuan Province, were utilized, and simulations on various harvesting machines experiencing random faults were conducted. Results indicated that the improved genetic algorithm reduced the optimal comprehensive scheduling cost during random fault occurrences by 47.49%, 19.60%, and 32.45% compared to the basic genetic algorithm and by 34.70%, 14.80%, and 24.40% compared to the ant colony algorithm. The improved algorithm showcases robust global optimization capabilities, high stability, and rapid convergence, offering effective emergency scheduling solutions in case of harvesting machine failures. Furthermore, a visual management system for agricultural machinery scheduling was developed to provide software support for optimizing agricultural machinery scheduling.

17.
Gene ; 896: 147994, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37977316

RESUMO

Craniosynostosis is one of the most common congenital craniofacial birth defects. The genetic etiology is complex, involving syndromic developmental diseases, chromosomal abnormalities, and monogenic non-syndromic diseases. Herein, we presented a proband of craniosynostosis, who firstly displayed structural abnormalities. This research conducted dynamic ultrasound monitoring a fetus with gradually developing intrauterine growth retardation (IUGR). A novel de novo variant c.41G > A: p.W14* in SMAD6 was identified by pedigree analysis and genetic examination approaches. Recombinant plasmid carrying wild-type sequence and mutant that carries c.41G > A in SMAD6 were constructed and transfected into HEK293T cells. mRNA and protein expression of SMAD6 were reduced in SMAD6 mutants compared to the wild type. Cycloheximide (CHX) treatment and si-UPF1 transfection rescued the SMAD6 mRNA expression in the mutant construct, indicating that c.41G > A: p.W14* in SMAD6 triggered nonsense-mediated mRNA degradation (NMD) process and thus led to haploinsufficiency of the protein product. Our study demonstrated that whole-exome sequencing (WES) was a powerful tool for further diagnosis and etiological identification once fetal malformation was detected by ultrasound. Novel de novo c.41G > A: p.W14* in SMAD6 is pathogenic and potentially leads to craniosynostosis via NMD process.


Assuntos
Craniossinostoses , Gravidez , Feminino , Humanos , Células HEK293 , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/genética , Feto , RNA Mensageiro/genética , China , Proteína Smad6/genética , Transativadores , RNA Helicases
18.
JAMA Ophthalmol ; 142(2): 133-139, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38236592

RESUMO

Importance: Anti-vascular endothelial growth factor (VEGF) treatment through intravitreal or subretinal administrations has been proven effective for VEGF-driven pediatric vitreoretinal diseases but are not feasible for advanced cases, such as shallow traction retinal detachments or peripheral circumferential retinal detachments which adhere to the lens. Intra-anterior chamber injection (IAcI) of anti-VEGF may be a viable alternative in such cases but needs evaluation. Objective: To investigate the effects and safety of IAcI of anti-VEGF to treat VEGF-driven pediatric vitreoretinal diseases. Design, Setting, and Participants: This was a retrospective observational case series study conducted at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine in China. The study included 14 eyes of 13 children diagnosed with vitreoretinal disease exhibiting elevated vascular activity between January and August 2023. Intervention: IAcI with ranibizumab. Main Outcomes and Measures: Retinal vascular abnormalities, vitreous hemorrhage resolution, and complications 1 month and 3 months after injection. Results: Of 13 patients included in this study, 12 were male. The mean age was 4.6 years (range, 1 month to 9 years). Six patients were diagnosed with familial exudative vitreoretinopathy, 4 with morning glory syndrome, 1 with retinopathy of prematurity, and 2 with chronic retinal detachments of unknown causes. At 1-month postoperative follow-up, vascular activity had decreased in 14 of 14 eyes. At 3-month follow-up, vascular activity had resolved in 7 of 14 eyes, persisted in 6 of 14 eyes, and reactivated in 1 of 14 eyes. On final observation, no complications were reported. Conclusions and Relevance: These findings support the possibility of treatment using IAcI with ranibizumab to decrease retinal vascular abnormalities in familial exudative vitreoretinopathy or retinopathy of prematurity or related conditions, but further studies are needed to understand more precise benefits and risks. This approach might be considered in cases where intravitreal or subretinal injection are not feasible, recognizing the limitations of these findings and that longer-term outcomes still need to be monitored.


Assuntos
Descolamento Retiniano , Retinopatia da Prematuridade , Recém-Nascido , Humanos , Masculino , Criança , Pré-Escolar , Feminino , Ranibizumab , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Descolamento Retiniano/etiologia , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/tratamento farmacológico , Vitreorretinopatias Exsudativas Familiares/complicações , Vitreorretinopatias Exsudativas Familiares/tratamento farmacológico , Injeção Intracameral , China , Estudos Retrospectivos , Injeções Intravítreas , Bevacizumab
19.
Rev Sci Instrum ; 94(5)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37166248

RESUMO

The difficulties in early fault diagnosis of bearings mainly include two aspects: first, the initial damage size of the bearing is small, and the abnormal vibration caused by slight damage to the bearing is very weak. Second, vibration signals collected in actual industrial environments always contain strong noise interference. Therefore, traditional diagnostic procedures are not satisfactory. To address these challenges, this work provides a hybrid model combining frequency-weighted energy operator (FWEO) with power spectrum fusion (PSF) to identify weak fault features of bearings and detect different fault types. Different from traditional time-domain signal filtering, PSF is first used to reduce the interference of noise components in the power spectrum, which will not weaken the fault signal components during denoising. Second, the filtered signal is transformed into the time domain and FWEO is employed to further enhance the cyclic fault signal caused by the weak defect of the bearing. Finally, the existence of a fault is identified by observing the squared envelope spectrum of the signal. The effectiveness of the proposed hybrid model is demonstrated through two simulated fault signals and three different experimental fault signals. The results show that the proposed model has high anti-noise performance and robustness and can extract the fault frequency well.

20.
Mater Horiz ; 10(2): 625-631, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36515011

RESUMO

A new heteronuclear EuII-MnII complex [Eu(N2O6)]MnBr4 (N2O6 = 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) is designed and synthesized, which shows an intense green emission from MnII with a near-unity photoluminescence quantum yield. Measurement of excited-state dynamics demonstrated the sensitization process from EuII to MnII, which represents the first example of f → d molecular sensitization. Due to the large optical absorption cross-section of the EuII center, [Eu(N2O6)]MnBr4 shows an emission intensity 7 to 2500 times stronger than that of the SrII-MnII control complex [Sr(N2O6)]MnBr4 upon the excitation of near ultraviolet to blue light.

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