Ligand-Induced Red-Emitting Copper Nanoclusters for Selective Fluorescence Determination of Aluminum Ions.

Monitoring levels of excessive aluminum ions (Al3+) is crucial as it can harm the immune system, reduce enzyme activity, cause cell death, and damage environmental and biological systems. Developing a fast and efficient Al3+ ion determination method is the key to addressing this issue. In this work, red-emitting fluorescent copper nanoclusters (CuNCs) were synthesized using N-acetyl-l-cysteine (NAC) as a ligand and CuCl2·2H2O through a facile procedure. The NAC-CuNCs exhibited a large Stokes shift and displayed remarkable luminescence properties. A method for detecting Al3+ through a fluorescence probe was proposed. Its fluorescence mechanism was also explored. The probe showed rapid responsiveness (within 1 min) to Al3+ ion determination. The detection limit for Al3+ was found to be 19.7 nM, which is significantly lower than the WHO's value and most reports, with a linear range of 0-52.9 µM. The determination of Al3+ concentrations in actual water using the fluorescence probe yielded satisfactory outcomes. Moreover, the visual detection of Al3+ ions was also achieved through a smartphone, which can enhance its fast and practical detection.

Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice.

The melanocortin-3 receptor (MC3R) regulates GABA release from agouti-related protein (AgRP) nerve terminals and thus tonically suppresses multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of the MC3R and the melanocortin system in regulating the response to various anorexigenic agents. The genetic deletion or pharmacological inhibition of the MC3R, or subthreshold doses of an MC4R agonist, improved the dose responsiveness to glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor leptin demonstrated that increased sensitivity to anorectic agents was a generalized result of MC3R antagonism. We observed enhanced neuronal activation in multiple hypothalamic nuclei using Fos IHC following low-dose liraglutide in MC3R-KO mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits that control multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r-/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R agonists may have value in enhancing the dose-response range of obesity therapeutics.

Construction and validation of a risk prediction model for postoperative ICU admission in patients with colorectal cancer: clinical prediction model study.

BACKGROUND: Transfer to the ICU is common following non-cardiac surgeries, including radical colorectal cancer (CRC) resection. Understanding the judicious utilization of costly ICU medical resources and supportive postoperative care is crucial. This study aimed to construct and validate a nomogram for predicting the need for mandatory ICU admission immediately following radical CRC resection. METHODS: Retrospective analysis was conducted on data from 1003 patients who underwent radical or palliative surgery for CRC at Ningxia Medical University General Hospital from August 2020 to April 2022. Patients were randomly assigned to training and validation cohorts in a 7:3 ratio. Independent predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression in the training cohort to construct the nomogram. An online prediction tool was developed for clinical use. The nomogram's calibration and discriminative performance were assessed in both cohorts, and its clinical utility was evaluated through decision curve analysis (DCA). RESULTS: The final predictive model comprised age (P = 0.003, odds ratio [OR] 3.623, 95% confidence interval [CI] 1.535-8.551); nutritional risk screening 2002 (NRS2002) (P = 0.000, OR 6.129, 95% CI 2.920-12.863); serum albumin (ALB) (P = 0.013, OR 0.921, 95% CI 0.863-0.982); atrial fibrillation (P = 0.000, OR 20.017, 95% CI 4.191-95.609); chronic obstructive pulmonary disease (COPD) (P = 0.009, OR 8.151, 95% CI 1.674-39.676); forced expiratory volume in 1 s / Forced vital capacity (FEV1/FVC) (P = 0.040, OR 0.966, 95% CI 0.935-0.998); and surgical method (P = 0.024, OR 0.425, 95% CI 0.202-0.891). The area under the curve was 0.865, and the consistency index was 0.367. The Hosmer-Lemeshow test indicated excellent model fit (P = 0.367). The calibration curve closely approximated the ideal diagonal line. DCA showed a significant net benefit of the predictive model for postoperative ICU admission. CONCLUSION: Predictors of ICU admission following radical CRC resection include age, preoperative serum albumin level, nutritional risk screening, atrial fibrillation, COPD, FEV1/FVC, and surgical route. The predictive nomogram and online tool support clinical decision-making for postoperative ICU admission in patients undergoing radical CRC surgery. TRIAL REGISTRATION: Despite the retrospective nature of this study, we have proactively registered it with the Chinese Clinical Trial Registry. The registration number is ChiCTR2200062210, and the date of registration is 29/07/2022.

Simultaneous reconstruction of 3D fluorescence distribution and object surface using structured light illumination and dual-camera detection.

Fluorescence molecular tomography (FMT) serves as a noninvasive modality for visualizing volumetric fluorescence distribution within biological tissues, thereby proving to be an invaluable imaging tool for preclinical animal studies. The conventional FMT relies upon a point-by-point raster scan strategy, enhancing the dataset for subsequent reconstruction but concurrently elongating the data acquisition process. The resultant diminished temporal resolution has persistently posed a bottleneck, constraining its utility in dynamic imaging studies. We introduce a novel system capable of simultaneous FMT and surface extraction, which is attributed to the implementation of a rapid line scanning approach and dual-camera detection. The system performance was characterized through phantom experiments, while the influence of scanning line density on reconstruction outcomes has been systematically investigated via both simulation and experiments. In a proof-of-concept study, our approach successfully captures a moving fluorescence bolus in three dimensions with an elevated frame rate of approximately 2.5 seconds per frame, employing an optimized scan interval of 5 mm. The notable enhancement in the spatio-temporal resolution of FMT holds the potential to broaden its applications in dynamic imaging tasks, such as surgical navigation.

Digital economy's role in shaping carbon emissions in the construction field: Insights from Chinese cities.

Achieving net-zero greenhouse gas emissions in the construction sector is essential to sustainable development policy. Previous studies have ignored the impact of the digital economy on carbon emissions in the construction industry. Using relevant city-level data from China from 2011 to 2021 and employing ArcGIS and Stata software, this study examines the current status of carbon emissions from the construction industry and investigates the impact of the digital economy on these emissions. The findings reveal that (1) from 2011 to 2021, carbon emissions of the construction industry have a pattern of decreasing-increasing-decreasing-increasing across the country. There is an increasing concentration of areas with high and relatively high carbon discharges in Heilongjiang, Jilin, Ningxia, Inner Mongolia, Shanxi, Guangxi, and Guizhou. (2) The standard deviation ellipse indicates the core area of carbon emissions in China's construction industry is moving northeast and becoming more decentralized. (3) Through a series of robustness tests, the digital economy has been proven to effectively reduce carbon emissions from the construction sector in municipal areas. (4) In severely cold regions, mild regions, and high-population-density cities, the digital economy reduces building sector's carbon output. However, it stimulates carbon emissions in the hot summer and cold winter regions. (5) Mechanism tests show that the digital economy reduces China's urban construction carbon emissions by fostering technological progress and green innovation. Urban resilience further strengthens the contribution of the digital economy to reducing carbon discharges in the urban construction sector of China. This article presents empirical evidence demonstrating how the digital economy empowers the construction industry to curtail emissions.

First-Principles Study on Janus-Structured Sc2CX2/Sc2CY2 (X, Y = F, Cl, Br) Heterostructures for Solar Energy Conversion.

Two-dimensional van der Waals heterostructures have good application prospects in solar energy conversion due to their excellent optoelectronic performance. In this work, the electronic structures of Sc2CF2/Sc2CCl2, Sc2CF2/Sc2CBr2, and Sc2CCl2/Sc2CBr2 heterostructures, as well as their properties in photocatalysis and photovoltaics, have been comprehensively studied using the first-principles method. Firstly, both of the three thermodynamically and dynamically stable heterostructures are found to have type-II band alignment with band gap values of 0.58 eV, 0.78 eV, and 1.35 eV. Meanwhile, the photogenerated carriers in Sc2CF2/Sc2CCl2 and Sc2CF2/Sc2CBr2 heterostructures are predicated to follow the direct Z-scheme path, enabling their abilities for water splitting. As for the Sc2CCl2/Sc2CBr2 heterostructure, its photovoltaic conversion efficiency is estimated to be 20.78%. Significantly, the light absorption coefficients of Sc2CF2/Sc2CCl2, Sc2CF2/Sc2CBr2, and Sc2CCl2/Sc2CBr2 heterostructures are enhanced more than those of the corresponding monolayers. Moreover, biaxial strains have been observed to considerably tune the aforementioned properties of heterostructures. All the theoretical results presented in this work demonstrate the application potential of Sc2CX2/Sc2CY2 (X, Y = F, Cl, Br) heterostructures in photocatalysis and photovoltaics.

Advances in 2,3-Dimethylmaleic Anhydride (DMMA)-Modified Nanocarriers in Drug Delivery Systems.

Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

Duck pan-genome reveals two transposon insertions caused bodyweight enlarging and white plumage phenotype formation during evolution.

Structural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan-genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan-genome together with high-depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE-derived SVs anchoring in a gene body or regulatory region are linked to duck's domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan-genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.

Distance-related functional reorganization predicts motor outcome in stroke patients.

BACKGROUND: Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. METHODS: In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. RESULTS: Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. CONCLUSIONS: The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. TRIAL REGISTRATION: All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

Learning and depicting lobe-based radiomics feature for COPD Severity staging in low-dose CT images.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning. METHODS: The retrospective study included 530 hospital patients. A lobe-based radiomics method was proposed to classify COPD severity using computed tomography (CT) images. First, we segmented the lung lobes with a convolutional neural network model. Secondly, the radiomic features of each lung lobe are extracted from CT images, the features of the five lung lobes are merged, and the selection of features is accomplished through the utilization of a variance threshold, t-Test, least absolute shrinkage and selection operator (LASSO). Finally, the COPD severity was classified by a support vector machine (SVM) classifier. RESULTS: 104 features were selected for staging COPD according to the Global initiative for chronic Obstructive Lung Disease (GOLD). The SVM classifier showed remarkable performance with an accuracy of 0.63. Moreover, an additional set of 132 features were selected to distinguish between milder (GOLD I + GOLD II) and more severe instances (GOLD III + GOLD IV) of COPD. The accuracy for SVM stood at 0.87. CONCLUSIONS: The proposed method proved that the novel lobe-based radiomics method can significantly contribute to the refinement of COPD severity staging. By combining radiomic features from each lung lobe, it can obtain a more comprehensive and rich set of features and better capture the CT radiomic features of the lung than simply observing the lung as a whole.

Advancing vaccine development: Evaluation of a mannose-modified lipid nanoparticle-based candidate for African swine fever p30 mRNA vaccine eliciting robust immune response in mice.

The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4+ and CD8+ T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).

The pyrexia channel remodels egg-laying of Liriomyza huidobrensis in response to temperature change.

BACKGROUND: The pea leafminer, Liriomyza huidobrensis, is one of the most important insect pests on vegetables and ornamentals. The survival and egg-laying behavior of leafminers are markedly affected by the environment temperature. However, the mechanisms underlying the relationship between egg-laying and temperature are still largely unknown. RESULTS: Here, we find that leafminers have evolved an adaptive strategy to overcome the stress from high or low temperature by regulating oviposition-punching plasticity. We further show that this oviposition-punching plasticity is mediated by the expression of pyx in the ovipositor when subjected to disadvantageous temperature. Specifically, down-regulation of pyx expression in leafminers under low temperature stress led to a significant decrease in the swing numbers of ovipositor and puncture area of the egg spot, and consequently the lower amount of egg-laying compared to leafminers at ambient temperature. Conversely, activation of pyx expression under high temperature stress increased the swing numbers and puncture area, still resulting in a reduction of egg-laying amount. CONCLUSION: Thereby, leafminers are able to coordinate pyx channel expression level and accordingly depress the oviposition. Our study uncovers a molecular mechanism underlying the adaptive strategy in insects that can avoid disadvantageous temperature for reproducing offspring. © 2024 Society of Chemical Industry.

Are vacuolar dynamics crucial factors for plant cell division and differentiation?

Vacuoles are the largest membrane-bound organelles in plant cells, critical for development and environmental responses. Vacuolar dynamics indicate reversible changes of vacuoles in morphology, size, or numbers. In this review, we summarize current understandings of vacuolar dynamics in different types of plant cells, biological processes associated with vacuolar dynamics, and regulators controlling vacuolar dynamics. Specifically, we point out the possibility that vacuolar dynamics play key roles in cell division and differentiation, which are controlled by the nucleus. Finally, we propose three routes through which vacuolar dynamics actively participate in nucleus-controlled cellular activities.

Metabolic cross-feeding between the competent degrader Rhodococcus sp. strain p52 and an incompetent partner during catabolism of dibenzofuran: Understanding the leading and supporting roles.

Microbial interactions, particularly metabolic cross-feeding, play important roles in removing recalcitrant environmental pollutants; however, the underlying mechanisms involved in this process remain unclear. Thus, this study aimed to elucidate the mechanism by which metabolic cross-feeding occurs during synergistic dibenzofuran degradation between a highly efficient degrader, Rhodococcus sp. strain p52, and a partner incapable of utilizing dibenzofuran. A bottom-up approach combined with pairwise coculturing was used to examine metabolic cross-feeding between strain p52 and Arthrobacter sp. W06 or Achromobacter sp. D10. Pairwise coculture not only promoted bacterial pair growth but also facilitated dibenzofuran degradation. Specifically, strain p52, acting as a donor, released dibenzofuran metabolic intermediates, including salicylic acid and gentisic acid, for utilization and growth, respectively, by the partner strains W06 and D10. Both salicylic acid and gentisic acid exhibited biotoxicity, and their accumulation inhibited dibenzofuran degradation. The transcriptional activity of the genes responsible for the catabolism of dibenzofuran and its metabolic intermediates was coordinately regulated in strain p52 and its cocultivated partners, thus achieving synergistic dibenzofuran degradation. This study provides insights into microbial metabolic cross-feeding during recalcitrant environmental pollutant removal.

Lanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo.

Nanothermometers enable the detection of temperature changes at the microscopic scale, which is crucial for elucidating biological mechanisms and guiding treatment strategies. However, temperature monitoring of micron-scale structures in vivo using luminescent nanothermometers remains challenging, primarily due to the severe scattering effect of biological tissue that compromises the imaging resolution. Herein, a lanthanide luminescence nanothermometer with a working wavelength beyond 1500 nm is developed to achieve high-resolution temperature imaging in vivo. The energy transfer between lanthanide ions (Er3+ and Yb3+) and H2O molecules, called the environment quenching assisted downshifting process, is utilized to establish temperature-sensitive emissions at 1550 and 980 nm. Using an optimized thin active shell doped with Yb3+ ions, the nanothermometer's thermal sensitivity and the 1550 nm emission intensity are enhanced by modulating the environment quenching assisted downshifting process. Consequently, minimally invasive temperature imaging of the cerebrovascular system in mice with an imaging resolution of nearly 200 µm is achieved using the nanothermometer. This work points to a method for high-resolution temperature imaging of micron-level structures in vivo, potentially giving insights into research in temperature sensing, disease diagnosis, and treatment development.

Integrated transcriptomic analysis systematically reveals the heterogeneity and molecular characterization of cancer-associated fibroblasts in osteosarcoma.

BACKGROUND: Osteosarcoma (OS), with a peak incidence during the adolescent growth spurt, is correlated with poor prognosis for its high malignancy. The tumor microenvironment (TME) is highly complicated, with frequent interactions between tumor and stromal cells. The cancer-associated fibroblasts (CAFs) in the TME have been considered to actively involve in the progression, metastasis, and drug resistance of OS. This study aimed to characterize cellular heterogeneity and molecular characterization in CAFs subtypes and explore the potential targeting therapeutic strategies to improve the prognosis of OS patients. METHODS: The single-cell atlas of human OS tumor lesions were constructed from the GEO database. Then significant marker genes and potential biological functions for each CAFs subtype were identified and explored using the Seurat R package. Next, by performing the survival analyses and constructing the risk scores for CAFs subtypes, we aimed to identify and characterize the prognostic values of specific marker genes and different CAFs subtypes. Furthermore, we explored the therapeutic targets and innovative drugs targeting different CAFs subtypes based on the GDSC database. Finally, prognoses related CAFs subtypes were further validated through immunohistochemistry (IHC) on clinical OS specimens. RESULTS: Overall, nine main cell clusters and five subtypes of CAFs were identified. The differentially expressed marker genes for each CAFs clusters were then identified. Moreover, through Gene Ontology (GO) enrichment analysis, we defined the CAFs_2 (upregulated CXCL14 and C3), which was closely related to leukocyte migration and chemotaxis, as inflammatory CAFs (iCAFs). Likewise, we defined the CAFs_4 (upregulated CD74, HLA-DRA and HLA-DRB1), which was closely related to antigen process and presentation, as antigen-presenting CAFs (apCAFs). Furthermore, Kaplan-Meier analyses showed that CAFs_2 and CAFs_4 were correlated with poor clinical prognosis of OS patients. Meanwhile, therapeutic drugs targeting CAFs_2 and CAFs_4, such as 17-AAG/Docetaxel/Bleomycin and PHA-793887/NG-25/KIN001-102, were also explored, respectively. Finally, IHC assay confirmed the abundant CAFs_2 and CAFs_4 subtypes infiltration in the OS microenvironment compared with adjacent tissues. CONCLUSION: Our study revealed the diversity, complexity, and heterogeneity of CAFs in OS, and complemented the single-cell atlas in OS TME.

Pd-Catalyzed Cascade Cyclization/Thiocarbonylation with Thioformates: Synthesis of Thioester-Functionalized Oxindoles.

A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.

Single-pixel p-graded-n junction spectrometers.

Ultra-compact spectrometers are becoming increasingly popular for their promising applications in biomedical analysis, environmental monitoring, and food safety. In this work, we report a single-pixel-photodetector spectrometer with a spectral range from 480 nm to 820 nm, based on the AlGaAs/GaAs p-graded-n junction with a voltage-tunable optical response. To reconstruct the optical spectrum, we propose a tailored method called Neural Spectral Fields (NSF) that leverages the unique wavelength and bias-dependent responsivity matrix. Our spectrometer achieves a high spectral wavelength accuracy of up to 0.30 nm and a spectral resolution of up to 10 nm. Additionally, we demonstrate the high spectral imaging performance of the device. The compatibility of our demonstration with the standard III-V process greatly accelerates the commercialization of miniaturized spectrometers.

Identification of two novel large deletions in FBN1 gene by next-generation sequencing and multiplex ligation-dependent probe amplification.

BACKGROUND: Mutations in fibrillin-1 (FBN1) are known to be associated with Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Most FBN1 mutations are missense or nonsense mutations. Traditional molecular genetic testing for the FBN1 gene, like Sanger sequencing, may miss disease-causing mutations in the gene's regulatory regions or non-coding sequences, as well as partial or complete gene deletions and duplications. METHODS: Next-generation sequencing, multiplex ligation-dependent probe amplification and gap PCR were conducted on two MFS patients to screen for disease-causing mutations. RESULTS: We identified two large deletions in FBN1 from two MFS patients. One patient had a 0.23 Mb deletion (NC_000015.9:g.48550506_48779360del) including 5'UTR-exon6 of FBN1. The other patient harbored a 1416 bp deletion (NC_000015.9:g.48410869_48412284del) affecting the last exon, exon 66, of the FBN1 gene. CONCLUSION: Our results expanded the number of large FBN1 deletions and highlighted the importance of screening for large deletions in FBN1 in clinical genetic testing, especially for those with the classic MFS phenotype.