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1.
Artigo em Inglês | MEDLINE | ID: mdl-39356954

RESUMO

Flexible electronics can seamlessly adhere to human skin or internal tissues, enabling the collection of physiological data and real-time vital sign monitoring in home settings, which give it the potential to revolutionize chronic disease management and mitigate mortality rates associated with sudden illnesses, thereby transforming current medical practices. However, the development of flexible electronic devices still faces several challenges, including issues pertaining to material selection, limited functionality, and performance instability. Among these challenges, the choice of appropriate materials, as well as their methods for film formation and patterning, lays the groundwork for versatile device development. Establishing stable interfaces, both internally within the device and in human-machine interactions, is essential for ensuring efficient, accurate, and long-term monitoring in health electronics. This review aims to provide an overview of critical fabrication steps and interface optimization strategies in the realm of flexible health electronics. Specifically, we discuss common thin film processing methods, patterning techniques for functional layers, interface challenges, and potential adjustment strategies. The objective is to synthesize recent advancements and serve as a reference for the development of innovative flexible health monitoring devices.

2.
Adv Mater ; : e2409564, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39374000

RESUMO

Perovskite nanocrystals (PNCs) are promising luminescent materials for electronic color displays due to their high luminescence efficiency, widely-tunable emission wavelengths, and narrow emission linewidth. Their application in emerging display technologies necessitates precise micron-scale patterning while maintaining good optical performance. Although photolithography is a well-established micro-patterning technique in the industry, conventional processes are incompatible with PNCs as the use of polar solvents can damage the ionic PNCs, causing severe luminescence quenching. Here, we report the rational design and synthesis of a new bidentate photo-crosslinkable ligand for the direct photo-patterning of PNCs. Each ligand contains two photosensitive acrylate groups and two carboxylate groups, and is introduced to the PNCs via an entropy-driven ligand exchange process. In a close-packed thin film, the acrylate ligands photo-polymerize and crosslink under ultraviolet light, rendering the PNCs insoluble in developing solvents. A high-density crosslinked PNC film with an optical density of 1.1 is attained at 1.4 µm thickness, surpassing industry requirements on the absorption coefficient. Micron-scale patterning is further demonstrated using direct laser writing, producing well-defined 20 µm features. This study thus offers an effective and versatile approach for micro-patterning PNCs, and may also be broadly applicable to other nanomaterial systems.

3.
J Surg Res ; 302: 925-935, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39276425

RESUMO

INTRODUCTION: A common treatment for large deep-to-full-thickness burns is excision and grafting with a widely meshed split-thickness skin graft (mSTSG). Due to the differential healing of the interstices and adhered split-thickness skin graft, wound patterning and delayed wound healing are common outcomes of this treatment. Delayed healing may increase infection rates and wound care requirements, while wound patterning may be psychologically and aesthetically consequential for patients. Autologous skin cell suspension (ASCS) can be used to "over spray" a meshed autograft. It was hypothesized that the use of ASCS combined with mSTSG would increase the rate of wound healing and decrease patterning in healed burn wounds. METHODS: Full-thickness burns or excisional wounds (n = 8 each) were created in red Duroc pigs and received 4:1 mSTSGs after wound bed preparation. Half of the wounds received ASCS and half did not at the time of grafting. Percent re-epithelialization, patterning, rete ridge ratio, cellularity, dermal and epidermal thickness, immunofluorescent S100ß staining, and melanin index were assessed for each scar. RESULTS: Wounds that received ASCS exhibited increased rates of re-epithelialization (burn +ACSC versus burn-ASCS; day 3 (53.9 ± 3.1 versus 34.3 ± 3.3, P = 0.009): day 5 (68.1 ± 1.6 versus 40.8 ± 3.2, P < 0.001)). Excision +ASCS versus excision-ASCS; day 7 (98.1 ± 1.2 versus 86.4 ± 2.0, day 7 P = 0.022) compared to wounds not treated with ASCS. There was no difference in rete ridge ratio, cellularity, dermal thickness, epidermal thickness, S100ß staining, melanin index, or patterning was measured between wounds that received ASCS and those that did not. CONCLUSIONS: The addition of ASCS to 4:1 mSTSGs leads to increased rate of wound healing but does not impact the degree of patterning in this model, suggesting that ASCS application likely robustly transfers keratinocytes but not functioning melanocytes at acute timepoints.

4.
Ann Bot ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240138

RESUMO

BACKGROUND AND AIMS: A hierarchical micro-topography of ridges and steps renders the trap rim of carnivorous Nepenthes pitcher plants unusually wettable, and slippery for insects when wet. This complex three-dimensional epidermis structure forms, hidden from plain sight, inside the still-closed developing pitcher bud. Here, we reveal the sequence of epidermal patterning events that shape the trap rim. By linking this sequence to externally visible markers of bud development, we provide a framework for targeting individual stages of surface development in future studies. METHODS: We used cryo-scanning electron microscopy to investigate the detailed morphogenesis and epidermal patterning of the Nepenthes x hookeriana pitcher rim. In addition, we collected morphometric and qualitative data from developing pitcher traps including those sampled for microscopy. KEY RESULTS: We identified three consecutive patterning events. First, strictly oriented cell divisions resulted in radially aligned rows of cells and established a macroscopic ridge-and-groove pattern. Next, conical papillate cells formed, and papillae elongated towards the trap interior, increasingly overlapping adjacent cells and eventually forming continuous microscopic ridges. In between these ridges, the flattened papillae formed acutely angled arched steps. Finally, the cells elongated radially, thereby establishing the convex collar shape of the rim. This general sequence of surface development also showed a spatial progression from the outer to the inner trap rim edge, with several consecutive developmental stages co-occurring at any given time. CONCLUSIONS: We demonstrate that the complex surface microtopography of the Nepenthes pitcher rim develops by sequentially combining widespread, evolutionarily conserved epidermal patterning processes in a new way. This makes the Nepenthes trap rim an excellent model for studying epidermal patterning mechanisms in leaves.

5.
Front Cell Dev Biol ; 12: 1429782, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239564

RESUMO

Cdon and boc are members of the cell adhesion molecule subfamily III Ig/fibronectin. Although they have been reported to be involved in muscle and neural development at late developmental stage, their early roles in embryonic development remain unknown. Here, we discovered that in zebrafish, cdon, but not boc, is expressed in dorsal forerunner cells (DFCs) and the epithelium of Kupffer's vesicle (KV), suggesting a potential role for cdon in organ left-right (LR) patterning. Further data showed that liver and heart LR patterning were disrupted in cdon morphants and cdon mutants. Mechanistically, we found that loss of cdon function led to defect in DFCs clustering, reduced KV lumen, and defective cilia, resulting in randomized Nodal/spaw signaling and subsequent organ LR patterning defects. Additionally, predominant distribution of a cdon morpholino (MO) in DFCs caused defects in DFC clustering, KV morphogenesis, cilia number/length, Nodal/spaw signaling, and organ LR asymmetry, similar to those observed in cdon morphants and cdon -/- embryos, indicating a cell-autonomous role for cdon in regulating KV formation during LR patterning. In conclusion, our data demonstrate that during gastrulation and early somitogenesis, cdon is essential for proper DFC clustering, KV formation, and normal cilia, thereby playing a critical role in establishing organ LR asymmetry.

6.
Adv Mater ; : e2408770, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39252650

RESUMO

Patterning Metal-Organic Frameworks (MOFs) is essential for their use in sensing, electronics, photonics, and encryption technologies. However, current lithography methods are limited in their ability to pattern more than two MOFs, hindering the potential for creating advanced multifunctional surfaces. Additionally, balancing design flexibility, simplicity, and cost often results in compromises. This study addresses these challenges by combining Digital-Light Processing (DLP) with a capillary-assisted stop-flow system to enable multimaterial MOF patterning. It demonstrates the desktop fabrication of multiplexed arbitrary micropatterns across cm-scale areas while preserving the MOF's pore accessibility. The ink, consisting of a MOF crystal suspension in a low volatile solvent, a mixture of high molecular weight oligomers, and a photoinitiator, is confined by capillarity in the DLP projection area and quickly exchanged using syringe pumps. The versatility of this method is demonstrated by the direct printing of a ZIF-8-based luminescent oxygen sensor, a 5-component dynamic information concealment method, and a PCN-224-based colorimetric sensor for amines, covering disparate pore and analyte sizes. The multi-MOF capabilities, simplicity, and accessibility of this strategy pave the way for the facile exploration of MOF materials across a wide range of applications, with the potential to significantly accelerate the design-to-application cycle of MOF-based devices.

7.
Adv Healthc Mater ; : e2402199, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300854

RESUMO

Recently, it has been recognized that natural extracellular matrix (ECM) and tissues are viscoelastic, while only elastic properties have been investigated in the past. How the viscoelastic matrix regulates stem cell patterning is critical for cell-ECM mechano-transduction. Here, this study fabricated different methacrylated hyaluronic acid (HA) hydrogels using covalent cross-linking, consisting of two gels with similar elasticity (stiffness) but different viscoelasticity, and two gels with similar viscoelasticity but different elasticity (stiffness). Meanwhile, a second set of dual network hydrogels are fabricated containing both covalent and coordinated cross-links. Human spinal cord organoid (hSCO) patterning in HA hydrogels and co-culture with isogenic human blood vessel organoids (hBVOs) are investigated. The viscoelastic hydrogels promote regional hSCO patterning compared to the elastic hydrogels. More viscoelastic hydrogels can promote dorsal marker expression, while softer hydrogels result in higher interneuron marker expression. The effects of viscoelastic properties of the hydrogels become more dominant than the stiffness effects in the co-culture of hSCOs and hBVOs. In addition, more viscoelastic hydrogels can lead to more Yes-associated protein nuclear translocation, revealing the mechanism of cell-ECM mechano-transduction. This research provides insights into viscoelastic behaviors of the hydrogels during human organoid patterning with ECM-mimicking in vitro microenvironments for applications in regenerative medicine.

8.
Small ; : e2402759, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39301993

RESUMO

The advent of organic-inorganic hybrid metal halide perovskites has revolutionized photovoltaics, with polycrystalline thin films reaching over 26% efficiency and single-crystal perovskite solar cells (IC-PSCs) demonstrating ≈24%. However, research on single-crystal perovskites remains limited, leaving a crucial gap in optimizing solar energy conversion. Unlike polycrystalline films, which suffer from high defect densities and instability, single-crystal perovskites offer minimal defects, extended carrier lifetimes, and longer diffusion lengths, making them ideal for high-performance optoelectronics and essential for understanding perovskite material behavior. This review explores the advancements and potential of IC-PSCs, focusing on their superior efficiency, stability, and role in overcoming the limitations of polycrystalline counterparts. It covers device architecture, material composition, preparation methodologies, and recent breakthroughs, emphasizing the importance of further research to propel IC-PSCs toward commercial viability and future dominance in photovoltaic technology.

9.
Gut Microbes ; 16(1): 2398126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39254265

RESUMO

The intestine exhibits distinct characteristics along its length, with a substantial immune cell reservoir and diverse microbiota crucial for maintaining health. This study investigates how anatomical location and regional microbiota influence intestinal immune cell abundance. Using conventionally colonized and germ-free mice, segment-specific immune cell composition and microbial communities were assessed. Metagenomic sequencing analyzed microbiome variations, while flow cytometry and immunofluorescence examined immune cell composition. Microbiome composition varied significantly along the intestine, with diversity and abundance increasing from upper to lower segments. Immune cells showed distinct segment-specific patterning influenced by microbial colonization and localization. T cell subsets displayed varied dependence on microbiome presence and anatomical location. This study highlights locoregional differences in intestinal immune cell and microbiome composition, identifying immune subsets susceptible to microbiota presence. The findings provide context for understanding immune cell alterations in disease models.


Assuntos
Bactérias , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Animais , Camundongos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/imunologia , Intestinos/microbiologia , Intestinos/imunologia , Intestinos/citologia , Metagenômica , Vida Livre de Germes , Feminino , Subpopulações de Linfócitos T/imunologia , Masculino , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/citologia
10.
Curr Res Insect Sci ; 6: 100094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262636

RESUMO

The calcium dependent Calpain proteases are modulatory enzymes with important roles in cell cycle control, development and immunity. In the fly model Drosophila melanogaster Calpain A cleaves Cactus/IkappaB and consequently modifies Toll signals during embryonic dorsal-ventral (DV) patterning. Here we explore the role of Calpains in the hemiptera Rhodnius prolixus, an intermediate germband insect where the Bone Morphogenetic Protein (BMP) instead of the Toll pathway plays a major role in DV patterning. Phylogenetic analysis of Calpains in species ranging from Isoptera to Diptera indicates an increase of Calpain sequences in the R. prolixus genome and other hemimetabolous species. One locus encoding each of the CalpC, CalpD and Calp7 families, and seven Calpain A/B loci are present in the R. prolixus genome. Several predicted R. prolixus Calpains display a unique architecture, such as loss of Calcium-binding EF-hand domains and loss of catalytic residues in the active site CysPc domain, yielding catalytically dead Calpains A/B. Knockdown for one of these inactive Calpains results in embryonic DV patterning defects, with expansion of ventral and lateral gene expression domains and consequent failure of germ band elongation. In conclusion, our results reveal that Calpains may exert a conserved function in insect DV patterning, despite the changing role of the Toll and BMP pathways in defining gene expression territories along the insect DV axis.

11.
R Soc Open Sci ; 11(9): 241012, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39263454

RESUMO

This work demonstrates that unetched substrates can be reliably used in perovskite solar cell (PSC) fabrication. Chemical etching and laser patterning of the bottom electrodes are time- and resource-consuming processes. In particular, when testing novel conductive substrate materials, such as metallic or bio-based substrates, etching or patterning could be entirely unfeasible or could require significant process optimization. Avoiding these steps could accelerate research on PSCs, yet the literature shows no attempts to override these steps. Here, PSCs were fabricated and characterized using three-dimensionally printed holders with spring-loaded pins. We show that devices made on unetched substrates have, on average, a similar performance to those made on etched substrates (16 ± 1% and 16.0 ± 0.7%, respectively). Our study provides a new strategy for fabricating PSCs, particularly when etching and laser patterning are impractical.

12.
Nano Lett ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269918

RESUMO

Solution-processable electrodes are promising for next-generation electronics due to their simplicity, cost-effectiveness, and potential for large-area fabrication. However, current solution-processable electrodes based on conductive polymers, carbon-based compounds, and metal nanowires face challenges related to stability, patterning, and production scalability. Here we introduce a novel approach using 3D tin halide perovskites (THPs) combined with a photolithography-free solution patterning technique to fabricate solution-processed electrodes. We demonstrate the preparation of highly conductive CsSnI3 films (234.9 S cm-1) and the fabrication of patterned 35 × 35 perovskite electrode arrays on a 4-in. silicon wafer. These electrodes, used as source/drain electrodes in organic transistors, resulted in devices showing high uniformity and stability. This electrode fabrication strategy is also applicable to other 3D THPs like FASnI3 and MASnI3, showcasing versatility for diverse applications. The results highlight the feasibility and advantages of using 3D THPs as solution-processable electrodes, providing a new material system for the advancement of solution-processed electronics.

13.
Development ; 151(18)2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39302048

RESUMO

Much of the striking diversity of life on Earth has arisen from variations in the way that the same molecules and networks operate during development to shape and pattern tissues and organs into different morphologies. However, we still understand very little about the potential for diversification exhibited by different, highly conserved mechanisms during evolution, or, conversely, the constraints that they place on evolution. With the aim of steering the field in new directions, we focus on morphogen-mediated patterning and growth as a case study to demonstrate how conserved developmental mechanisms can adapt during evolution to drive morphological diversification and optimise functionality, and to illustrate how evolution algorithms and computational tools can be used alongside experiments to provide insights into how these conserved mechanisms can evolve. We first introduce key conserved properties of morphogen-driven patterning mechanisms, before summarising comparative studies that exemplify how changes in the spatiotemporal expression and signalling levels of morphogens impact the diversification of organ size, shape and patterning in nature. Finally, we detail how theoretical frameworks can be used in conjunction with experiments to probe the role of morphogen-driven patterning mechanisms in evolution. We conclude that morphogen-mediated patterning is an excellent model system and offers a generally applicable framework to investigate the evolution of developmental mechanisms.


Assuntos
Evolução Biológica , Padronização Corporal , Morfogênese , Padronização Corporal/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Transdução de Sinais , Modelos Biológicos
14.
Cell Rep ; 43(10): 114722, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39302834

RESUMO

Fat and Dachsous are evolutionarily conserved atypical cadherins that regulate polarized cell behaviors. In the Drosophila wing, they interact heterophilically between neighboring cells, localize asymmetrically to opposite cell ends, and control wing shape by regulating oriented cell rearrangements and divisions. Fat and Dachsous have 34 and 27 cadherin repeats, respectively, and previous work has identified trans interactions between their first four cadherin repeats. Here, we identify a second heterophilic binding site in their C-terminal cadherin repeats and show the conservation of this binding site in human Fat4 and Dachsous1. We provide evidence that both N- and C-terminal binding sites regulate the stability of Fat-Dachsous binding interactions and show that the N-terminal binding sites are partly dispensable for Fat-Dachsous function in vivo. Finally, we provide in vivo confirmation that the N-terminal repeats interact in an anti-parallel manner. We propose that multiple binding sites promote the clustering of Fat and Dachsous into a lattice-like array.

15.
BMC Biol ; 22(1): 212, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300453

RESUMO

BACKGROUND: Wnt signaling pathways play crucial roles in animal development. They establish embryonic axes, specify cell fates, and regulate tissue morphogenesis from the early embryo to organogenesis. It is becoming increasingly recognized that these distinct developmental outcomes depend upon dynamic interactions between multiple ligands, receptors, antagonists, and other pathway modulators, consolidating the view that a combinatorial "code" controls the output of Wnt signaling. However, due to the lack of comprehensive analyses of Wnt components in several animal groups, it remains unclear if specific combinations always give rise to specific outcomes, and if these combinatorial patterns are conserved throughout evolution. RESULTS: In this work, we investigate the combinatorial expression of Wnt signaling components during the axial patterning of the brachiopod Terebratalia transversa. We find that T. transversa has a conserved repertoire of ligands, receptors, and antagonists. These genes are expressed throughout embryogenesis but undergo significant upregulation during axial elongation. At this stage, Frizzled domains occupy broad regions across the body while Wnt domains are narrower and distributed in partially overlapping patches; antagonists are mostly restricted to the anterior end. Based on their combinatorial expression, we identify a series of unique transcriptional subregions along the anteroposterior axis that coincide with the different morphological subdivisions of the brachiopod larval body. When comparing these data across the animal phylogeny, we find that the expression of Frizzled genes is relatively conserved, whereas the expression of Wnt genes is more variable. CONCLUSIONS: Our results suggest that the differential activation of Wnt signaling pathways may play a role in regionalizing the anteroposterior axis of brachiopod larvae. More generally, our analyses suggest that changes in the receptor context of Wnt ligands may act as a mechanism for the evolution and diversification of the metazoan body axis.


Assuntos
Padronização Corporal , Via de Sinalização Wnt , Animais , Padronização Corporal/genética , Invertebrados/embriologia , Invertebrados/genética , Invertebrados/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Wnt/metabolismo , Proteínas Wnt/genética
16.
bioRxiv ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39282430

RESUMO

The family Chamaeleonidae comprises 228 species, boasting an extensive geographic spread and an array of evolutionary novelties and adaptations, but a paucity of genetic and molecular analyses. Veiled chameleon (Chamaeleo calyptratus) has emerged as a tractable research organism for the study of squamate early development and evolution. Here we report a chromosomal-level assembly and annotation of the veiled chameleon genome. We note a remarkable chromosomal conservation across squamates, but comparisons to more distant genomes reveal GC peaks correlating with ancestral chromosome fusion events. We subsequently identified the XX/XY region on chromosome 5, confirming environmental-independent sex determination in veiled chameleons. Furthermore, our analysis of the Hox gene family indicates that veiled chameleons possess the most complete set of 41 Hox genes, retained from an amniote ancestor. Lastly, the veiled chameleon genome has retained both ancestral paralogs of the Nodal gene, but is missing Dand5 and several other genes, recently associated with the loss of motile cilia during the establishment of left-right patterning. Thus, a complete veiled chameleon genome provides opportunities for novel insights into the evolution of reptilian genomes and the molecular mechanisms driving phenotypic variation and ecological adaptation.

17.
bioRxiv ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39257760

RESUMO

The cardiac conduction system (CCS) orchestrates the electrical impulses that enable coordinated contraction of the cardiac chambers. The T-box transcription factors TBX3 and TBX5 are required for cardiac conduction system development and associated with overlapping and distinct human cardiac conduction system diseases. We evaluated the coordinated role of Tbx3 and Tbx5 in the murine ventricular conduction system (VCS). We engineered a compound Tbx3:Tbx5 conditional knockout allele for both genes located in cis on mouse chromosome 5. Conditional deletion of both T-box transcriptional factors in the ventricular conduction system, using the VCS-specific Mink:Cre, caused loss of VCS function and molecular identity. Combined Tbx3 and Tbx5 deficiency in the adult VCS led to conduction defects, including prolonged PR and QRS intervals and elevated susceptibility to ventricular tachycardia. These electrophysiologic defects occurred prior to detectable alterations in cardiac contractility or histologic morphology, indicative of a primary conduction system defect. Tbx3:Tbx5 double knockout VCS cardiomyocytes revealed a transcriptional shift towards non-CCS-specialized working myocardium, suggesting reprogramming of their cellular identity. Furthermore, optical mapping revealed a loss of VCS-specific conduction system propagation. Collectively, these findings indicate that Tbx3 and Tbx5 coordinate to control VCS molecular fate and function, with implications for understanding cardiac conduction disorders in humans.

18.
HGG Adv ; 5(4): 100353, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39275801

RESUMO

Heterotaxy is a disorder characterized by severe congenital heart defects (CHDs) and abnormal left-right patterning in other thoracic or abdominal organs. Clinical and research-based genetic testing has previously focused on evaluation of coding variants to identify causes of CHDs, leaving non-coding causes of CHDs largely unknown. Variants in the transcription factor zinc finger of the cerebellum 3 (ZIC3) cause X-linked heterotaxy. We identified an X-linked heterotaxy pedigree without a coding variant in ZIC3. Whole-genome sequencing revealed a deep intronic variant (ZIC3 c.1224+3286A>G) predicted to alter RNA splicing. An in vitro minigene splicing assay confirmed the variant acts as a cryptic splice acceptor. CRISPR-Cas9 served to introduce the ZIC3 c.1224+3286A>G variant into human embryonic stem cells demonstrating pseudoexon inclusion caused by the variant. Surprisingly, Sanger sequencing of the resulting ZIC3 c.1224+3286A>G amplicons revealed several isoforms, many of which bypass the normal coding sequence of the third exon of ZIC3, causing a disruption of a DNA-binding domain and a nuclear localization signal. Short- and long-read mRNA sequencing confirmed these initial results and identified additional splicing patterns. Assessment of four isoforms determined abnormal functions in vitro and in vivo while treatment with a splice-blocking morpholino partially rescued ZIC3. These results demonstrate that pseudoexon inclusion in ZIC3 can cause heterotaxy and provide functional validation of non-coding disease causation. Our results suggest the importance of non-coding variants in heterotaxy and the need for improved methods to identify and classify non-coding variation that may contribute to CHDs.

19.
Front Genet ; 15: 1458953, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39315310

RESUMO

Objective: Copy number changes at Chromosomal 16p13.11 have been implicated in a variety of human diseases including congenital cardiac abnormalities. The clinical correlation of copy number variants (CNVs) in this region with developmental abnormalities remains controversial as most of the patients inherit the duplication from an unaffected parent. Methods: We performed CNV analysis on 164 patients with defective left-right (LR) patterning based on whole genome-exome sequencing (WG-ES) followed by multiplex ligation-dependent probe amplification (MLPA) validation. Most cases were accompanied with complex congenital heart disease (CHD). Results: CNVs at 16p13.11 were identified in a total of 21 cases, accounting for 12.80% (21/164) evaluated cases. We observed a marked overrepresentation of chromosome 16p13.11 duplications in cases when compared with healthy controls according to literature reports (15/164, 9.14% versus 0.09% in controls). Notably, in two independent family trios, de novo 16p13.11 micro-duplications were identified in two patients with laterality defects and CHD. Moreover, 16p13.11 micro-duplication was segregated with the disease in a family trio containing 2 affected individuals. Notably, five coding genes, NOMO1, PKD1P3, NPIPA1, PDXDC1, and NTAN1, were potentially affected by micro-CNV at 16p13.11 in these patients. Conclusion: Our study provides new family-trio based evidences to support 16p13.11 micro-duplications predispose individuals to defective cardiac left-right patterning and laterality disorder.

20.
Polymers (Basel) ; 16(18)2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39339077

RESUMO

The use of organic semiconductors in electronic devices, including transistors, sensors, and memories, unlocks innovative possibilities such as streamlined fabrication processes, enhanced mechanical flexibility, and potential new applications. Nevertheless, the increasing technical demand for patterning organic semiconductors requires greater integration and functional implementation. This paper overviews recent efforts to pattern organic semiconductors compatible with electronic devices. The review categorizes the contributions of organic semiconductor patterning approaches, such as surface-grafting polymers, capillary force lithography, wettability, evaporation, and diffusion in organic semiconductor-based transistors and sensors, offering a timely perspective on unconventional approaches to enable the patterning of organic semiconductors with a strong focus on the advantages of organic semiconductor utilization. In addition, this review explores the opportunities and challenges of organic semiconductor-based integration, emphasizing the issues related to patterning and interconnection.

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