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1.
Nature ; 630(8018): 878-883, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38718837

RESUMEN

The properties of polycrystalline materials are often dominated by defects; two-dimensional (2D) crystals can even be divided and disrupted by a line defect1-3. However, 2D crystals are often required to be processed into films, which are inevitably polycrystalline and contain numerous grain boundaries, and therefore are brittle and fragile, hindering application in flexible electronics, optoelectronics and separation1-4. Moreover, similar to glass, wood and plastics, they suffer from trade-off effects between mechanical strength and toughness5,6. Here we report a method to produce highly strong, tough and elastic films of an emerging class of 2D crystals: 2D covalent organic frameworks (COFs) composed of single-crystal domains connected by an interwoven grain boundary on water surface using an aliphatic bi-amine as a sacrificial go-between. Films of two 2D COFs have been demonstrated, which show Young's moduli and breaking strengths of 56.7 ± 7.4 GPa and 73.4 ± 11.6 GPa, and 82.2 ± 9.1 N m-1 and 29.5 ± 7.2 N m-1, respectively. We predict that the sacrificial go-between guided synthesis method and the interwoven grain boundary will inspire grain boundary engineering of various polycrystalline materials, endowing them with new properties, enhancing their current applications and paving the way for new applications.

2.
Nat Methods ; 20(8): 1159-1169, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37443337

RESUMEN

The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed using computational tools. Numerous such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools detected more than 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were validated using three orthogonal methods. Generally, tool-specific precision is high and similar (median of 98.8%, 96.3% and 95.5% for qPCR, RNase R and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant differentiators. Of note, precision values are lower when evaluating low-abundance circRNAs. We also show that the tools can be used complementarily to increase detection sensitivity. Finally, we offer recommendations for future circRNA detection and validation.


Asunto(s)
Benchmarking , ARN Circular , Humanos , ARN Circular/genética , ARN/genética , ARN/metabolismo , Análisis de Secuencia de ARN/métodos
3.
Genome Res ; 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35948368

RESUMEN

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

4.
Brief Bioinform ; 24(1)2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36562715

RESUMEN

As one of the most vital methods in drug development, drug repositioning emphasizes further analysis and research of approved drugs based on the existing large amount of clinical and experimental data to identify new indications of drugs. However, the existing drug repositioning methods didn't achieve enough prediction performance, and these methods do not consider the effectiveness information of drugs, which make it difficult to obtain reliable and valuable results. In this study, we proposed a drug repositioning framework termed DRONet, which make full use of effectiveness comparative relationships (ECR) among drugs as prior information by combining network embedding and ranking learning. We utilized network embedding methods to learn the deep features of drugs from a heterogeneous drug-disease network, and constructed a high-quality drug-indication data set including effectiveness-based drug contrast relationships. The embedding features and ECR of drugs are combined effectively through a designed ranking learning model to prioritize candidate drugs. Comprehensive experiments show that DRONet has higher prediction accuracy (improving 87.4% on Hit@1 and 37.9% on mean reciprocal rank) than state of the art. The case analysis also demonstrates high reliability of predicted results, which has potential to guide clinical drug development.


Asunto(s)
Biología Computacional , Reposicionamiento de Medicamentos , Biología Computacional/métodos , Reposicionamiento de Medicamentos/métodos , Reproducibilidad de los Resultados , Exactitud de los Datos , Algoritmos
5.
Nucleic Acids Res ; 51(D1): D1029-D1037, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36318258

RESUMEN

Understanding gene expression patterns across different human cell types is crucial for investigating mechanisms of cell type differentiation, disease occurrence and progression. The recent development of single-cell RNA-seq (scRNA-seq) technologies significantly boosted the characterization of cell type heterogeneities in different human tissues. However, the huge number of datasets in the public domain also posed challenges in data integration and reuse. We present Human Universal Single Cell Hub (HUSCH, http://husch.comp-genomics.org), an atlas-scale curated database that integrates single-cell transcriptomic profiles of nearly 3 million cells from 185 high-quality human scRNA-seq datasets from 45 different tissues. All the data in HUSCH were uniformly processed and annotated with a standard workflow. In the single dataset module, HUSCH provides interactive gene expression visualization, differentially expressed genes, functional analyses, transcription regulators and cell-cell interaction analyses for each cell type cluster. Besides, HUSCH integrated different datasets in the single tissue module and performs data integration, batch correction, and cell type harmonization. This allows a comprehensive visualization and analysis of gene expression within each tissue based on single-cell datasets from multiple sources and platforms. HUSCH is a flexible and comprehensive data portal that enables searching, visualizing, analyzing, and downloading single-cell gene expression for the human tissue atlas.


Asunto(s)
Perfilación de la Expresión Génica , Análisis de la Célula Individual , Transcriptoma , Humanos , Diferenciación Celular , Bases de Datos Factuales , Análisis de Secuencia de ARN , Atlas como Asunto
6.
Nucleic Acids Res ; 51(D1): D1425-D1431, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36321662

RESUMEN

The Tumor Immune Single Cell Hub 2 (TISCH2) is a resource of single-cell RNA-seq (scRNA-seq) data from human and mouse tumors, which enables comprehensive characterization of gene expression in the tumor microenvironment (TME) across multiple cancer types. As an increasing number of datasets are generated in the public domain, in this update, TISCH2 has included 190 tumor scRNA-seq datasets covering 6 million cells in 50 cancer types, with 110 newly collected datasets and almost tripling the number of cells compared with the previous release. Furthermore, TISCH2 includes several new functions that allow users to better utilize the large-scale scRNA-seq datasets. First, in the Dataset module, TISCH2 provides the cell-cell communication results in each dataset, facilitating the analyses of interacted cell types and the discovery of significant ligand-receptor pairs between cell types. TISCH2 also includes the transcription factor analyses for each dataset and visualization of the top enriched transcription factors of each cell type. Second, in the Gene module, TISCH2 adds functions for identifying correlated genes and providing survival information for the input genes. In summary, TISCH2 is a user-friendly, up-to-date and well-maintained data resource for gene expression analyses in the TME. TISCH2 is freely available at http://tisch.comp-genomics.org/.


Asunto(s)
Neoplasias , Análisis de Expresión Génica de una Sola Célula , Microambiente Tumoral , Animales , Humanos , Ratones , Perfilación de la Expresión Génica/métodos , Neoplasias/genética , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Análisis de Expresión Génica de una Sola Célula/métodos , Transcriptoma , Microambiente Tumoral/genética , Conjuntos de Datos como Asunto
7.
J Am Chem Soc ; 146(5): 3449-3457, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38268407

RESUMEN

The core features of covalent organic frameworks (COFs) are crystallinity and porosity. However, the synthesis of single-crystal COFs with monomers of diverse reactivity and adjustment of their pore structures remain challenging. Here, we show that linkers that can react with a node to form single-crystal COFs can guide other linkers that form either COFs or amorphous polymers with the node to gain single-crystal COFs with mixed components, which are homogeneous on the unit cell scale with controlled ratios. With the linker-guided crystal growth method, we created nine types of single-crystal COFs with up to nine different components, which are more complex than any known crystal. The structure of the crystal adapted approximately to that of the main component, and its pore volume could be expanded up to 8.8%. Different components lead to complex and diverse pore structures and offer the possibilities to gain positive synergies, as exemplified by a bicomponent COF with 2200 and 733% SO2 uptake capacity of that of the two pure-component counterparts at 298 K and 0.002 bar. The selectivity for separation of SO2/CO2 ranges from 1230 to 4247 for flue gas based on ideal adsorbed solution theory, recording porous crystals. The bicomponent COF also exhibits a 1300% retention time of its pure-component counterparts for SO2 in a dynamic column breakthrough experiment for deep desulfurization.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38972436

RESUMEN

BACKGROUND & AIMS: There is limited clinical data regarding the additional yields of random biopsies during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for IBD patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis, and 16.20% in per-lesion analysis. The detection rate were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full HD equipment should consider incorporating RB in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.

9.
Anal Chem ; 96(19): 7558-7565, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38696396

RESUMEN

With a view to potentiometric sensing with minimal calibration requirements and high long-term stability, colloid-imprinted mesoporous (CIM) carbon was functionalized by the covalent attachment of a cobalt redox buffer and used as a new solid contact for ion-selective electrodes (ISEs). The CIM carbon surface was first modified by electroless grafting of a terpyridine ligand (Tpy-ph) using diazonium chemistry, followed by stepwise binding of Co(II) and an additional Tpy ligand to the grafted ligand, forming a bis(terpyridine) Co(II) complex, CIM-ph-Tpy-Co(II)-Tpy. Half a molar equivalent of ferrocenium tetrakis(3-chlorophenyl)borate was then used to partially oxidize the Co(II) complex. Electrodes prepared with this surface-attached CIM-ph-Tpy-Co(III/II)-Tpy redox buffer as a solid contact were tested as K+ sensors in combination with valinomycin as the ionophore and Dow 3140 silicone or plasticized poly(vinyl chloride) (PVC) as the matrixes for the ion-selective membrane (ISM). This solid contact is characterized by a redox capacitance of 3.26 F/g, ensuring a well-defined interfacial potential that underpins the transduction mechanism. By use of a redox couple as an internal reference element to control the phase boundary potential at the interface of the ISM and the CIM carbon solid contact, solid-contact ion-selective electrodes (SC-ISEs) with a standard deviation of E° as low as 0.3 mV for plasticized PVC ISMs and 3.5 mV for Dow 3140 silicone ISMs were obtained. Over 100 h, these SC-ISEs exhibit an emf drift of 20 µV/h for plasticized PVC ISMs and 62 µV/h for silicone ISMs. The differences in long-term stability and reproducibility between electrodes with ISMs comprising either a plasticized PVC or silicone matrix offer valuable insights into the effect of the polymeric matrix on sensor performance.

10.
Biochem Biophys Res Commun ; 708: 149770, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38518722

RESUMEN

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.


Asunto(s)
Altitud , Riñón , Ácido Tauroquenodesoxicólico , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Riñón/patología , Apoptosis , Estrés Oxidativo , Estrés del Retículo Endoplásmico
11.
Small ; 20(23): e2310166, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38145326

RESUMEN

Polarization photodetection taking advantage of the anisotropy of 2D materials shines brilliantly in optoelectronic fields owing to differentiating optical information. However, the previously reported polarization detections are mostly dependent on external power sources, which is not conducive to device integration and energy conservation. Herein, a 2D polar perovskite (CBA)2CsPb2Br7 (CCPB, CBA = 4-chlorobenzyllamine) has been successfully synthesized, which shows anticipated bulk photovoltaic effect (BPVE) with an open-circuited photovoltage up to ≈0.2 V. Devices based on CCPB monomorph fulfill a fascinating self-powered polarized photodetection with a large polarization ratio of 2.7 at room temperature. Moreover, CCPB features a high phase-transition temperature (≈475 K) which prompts such self-powered polarized photodetection in a large temperature window of device operation, since BPVE generated by spontaneous polarization can only exist in the polar structure prior to the phase transition. Further computational investigation reveals the introduction of CBA+ with a large dipole moment contributes to quite large polarization (17.5 µC cm-2) and further super high phase transition temperature of CCPB. This study will promote the application of 2D perovskite materials for self-powered polarized photodetection in high-temperature conditions.

12.
Small ; 20(26): e2308527, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38221686

RESUMEN

Flexible hydroelectric generators (HEGs) are promising self-powered devices that spontaneously derive electrical power from moisture. However, achieving the desired compatibility between a continuous operating voltage and superior current density remains a significant challenge. Herein, a textile-based van der Waals heterostructure is rationally designed between conductive 1T phase tungsten disulfide@carbonized silk (1T-WS2@CSilk) and carbon black@cotton (CB@Cotton) fabrics with an asymmetric distribution of oxygen-containing functional groups, which enhances the proton concentration gradients toward high-performance wearable HEGs. The vertically staggered 1T-WS2 nanosheet arrays on the CSilk fabric provide abundant hydrophilic nanochannels for rapid carrier transport. Furthermore, the moisture-induced primary battery formed between the active aluminum (Al) electrode and the conductive textiles introduces the desired electric field to facilitate charge separation and compensate for the decreased streaming potential. These devices exhibit a power density of 21.6 µW cm-2, an open-circuit voltage (Voc) of 0.65 V sustained for over 10 000 s, and a current density of 0.17 mA cm-2. This performance makes them capable of supplying power to commercial electronics and human respiratory monitoring. This study presents a promising strategy for the refined design of wearable electronics.

13.
Mol Carcinog ; 63(4): 677-687, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38362848

RESUMEN

N6 -methyladenosine (m6 A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m6 A modification patterns in tumor progression. However, the relationship between m6 A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m6 A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m6 A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m6 A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ2 test demonstrated a significant association between the levels of m6 A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m6 A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Secuenciación de Nanoporos , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Transcriptoma , Epigenoma , Epigénesis Genética , ARN , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética
14.
Clin Exp Immunol ; 217(1): 31-44, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38587448

RESUMEN

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/- mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.


Asunto(s)
Alérgenos , Asma , Interleucina-18 , Células Th17 , Células Th2 , Humanos , Interleucina-18/inmunología , Interleucina-18/sangre , Asma/inmunología , Asma/sangre , Animales , Células Th2/inmunología , Ratones , Femenino , Células Th17/inmunología , Masculino , Adulto , Alérgenos/inmunología , Persona de Mediana Edad , Regulación hacia Arriba/inmunología , Subunidad alfa del Receptor de Interleucina-18/inmunología , Subunidad alfa del Receptor de Interleucina-18/genética , Ovalbúmina/inmunología , Receptores de Interleucina-18/inmunología , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad , Pyroglyphidae/inmunología , Adulto Joven
15.
Brief Bioinform ; 23(4)2022 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-35641157

RESUMEN

Circular ribonucleic acids (RNAs) (circRNAs) are formed by covalently linking the downstream splice donor and the upstream splice acceptor. One of the most important functions of circRNAs is mainly exerted through binding RNA-binding proteins (RBPs). However, there is no efficient algorithm for identifying genome-wide circRNA-RBP interactions. Here, we developed a unique algorithm, circRIP, for identifying circRNA-RBP interactions from RNA immunoprecipitation sequencing (RIP-Seq) data. A simulation test demonstrated the sensitivity and specificity of circRIP. By applying circRIP, we identified 95 IGF2BP3-binding circRNAs based on the IGF2BP3 RIP-Seq dataset. We further identified 2823 and 1333 circRNAs binding to >100 RBPs in K562 and HepG2 cell lines, respectively, based on enhanced cross-linking immunoprecipitation (eCLIP) data, demonstrating the significance to survey the potential interactions between circRNAs and RBPs. In this study, we provide an accurate and sensitive tool, circRIP (https://github.com/bioinfolabwhu/circRIP), to systematically identify RBP and circRNA interactions from RIP-Seq and eCLIP data, which can significantly benefit the research community for the functional exploration of circRNAs.


Asunto(s)
ARN Circular , ARN , Genoma , Inmunoprecipitación , ARN/genética , ARN/metabolismo , Análisis de Secuencia de ARN
16.
Hepatology ; 78(1): 103-119, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35713976

RESUMEN

BACKGROUND AND AIMS: Succinate dehydrogenase enzyme (SDH) is frequently diminished in samples from patients with hepatocellular carcinoma (HCC), and SDH reduction is associated with elevated succinate level and poor prognosis in patients with HCC. However, the underlying mechanisms of how impaired SDH activity promotes HCC remain unclear. APPROACH AND RESULTS: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury-induced murine HCC models and patient samples. Subsequent RNA sequencing, hematoxylin and eosin staining, and immunohistochemistry analyses of HCC samples revealed that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. YAP/TAZ stability was greatly enhanced in SDHA/B-depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation, which facilitated the deNEDDylation of cullin1 and therefore disrupted the E3 ubiquitin ligase SCF ß-TrCP complex, consequently leading to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. CONCLUSIONS: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus binding SDH-deficient HCC cells to YAP/TAZ pathway and rendering these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in patients with HCC displaying reduced SDHA/B or elevated succinate levels.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias Hepáticas/patología , Transactivadores/metabolismo , Proteínas Señalizadoras YAP , Succinatos , Complejo II de Transporte de Electrones/metabolismo
17.
Cytokine ; 173: 156415, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37952311

RESUMEN

BACKGROUND: Endothelial nitric oxide (NO) produced by endothelial Nitric Oxide Synthase (eNOS) can promote the expression of pro-angiogenic cytokines and is favorable for angiogenesis. However, the relationship between NOS3 gene polymorphisms and genetic susceptibility to congenital heart disease (CHD) was still unclear. METHODS: We searched five databases including Pubmed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang, to find all studies on NOS3 gene polymorphisms and CHD. Rstudio was used to merge the data included in the study to obtain OR, 95%CI, and forest plots. RESULTS: Five relevant literatures were included, including three sites of NOS3 gene, rs1799983 (G894T), rs2070744 (T-786C), and rs7830 (G10T). Several models including the homozygous model of rs1799983 (G894T) gene polymorphism (TT VS GG: OR = 1.602, 95%CI: 1.098 âˆ¼ 2.337, P = 0.027), rs7830 (G10T) gene polymorphism allele model (A VS C: OR = 1.171, 95%CI: 1.029 âˆ¼ 1.333, P = 0.017), homozygous model (AA VS CC: OR = 1.474, 95%CI: 1.122 âˆ¼ 1.936, P = 0.005) and implicit model (AA VS CC + AC: OR = 1.451, 95%CI: 1.133 âˆ¼ 1.859, P = 0.003) indicated that there was a correlation. The results of the combined analysis of each gene model of rs2070744 (T-786C) gene polymorphism sites were not statistically significant, and their P values were all>0.05. CONCLUSION: rs1799983 (G894T) and rs7830 (G10T) polymorphic sites might play a role in the susceptibility of sporadic congenital heart disease and increase the risk of CHD. Yet, it is still necessary to expand the sample size and conduct more prospective/retrospective studies to confirm whether the rs2070744 (T-786C) polymorphism tended to increase the incidence of CHD.


Asunto(s)
Cardiopatías Congénitas , Óxido Nítrico Sintasa de Tipo III , Humanos , Óxido Nítrico Sintasa de Tipo III/genética , Estudios Retrospectivos , Estudios Prospectivos , Polimorfismo Genético , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles , Cardiopatías Congénitas/genética , Polimorfismo de Nucleótido Simple/genética , Genotipo
18.
Chemistry ; : e202401929, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818768

RESUMEN

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

19.
BMC Cancer ; 24(1): 596, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755542

RESUMEN

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Recurrencia Local de Neoplasia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Estudios Retrospectivos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/radioterapia , Esofagectomía , Adulto , Pronóstico , China/epidemiología , Estadificación de Neoplasias
20.
Langmuir ; 40(10): 5444-5454, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38427794

RESUMEN

Historically, research on silicotungstic-acid-based hydrogels has primarily focused on their adhesive properties, often at the expense of mechanical strength (cohesion). In this study, we present a novel approach to fabricate a polysaccharide hydrogel that harmoniously balances both adhesion and cohesion via interfacial hydrogen bonds. This hydrogel, composed of carboxymethyl cellulose (CMC), polyacrylamide (PAM), silicotungstic acid (SiW), and lithium chloride (LiCl), showcases a unique combination of properties: strain-responsive ionic conductivity, superior transparency, remarkable stretchability, and robust adhesion. Contrary to conventional PAM hydrogels, our PAM-SiW networked hydrogel addresses the common challenge of achieving good adhesion without compromising on cohesion. Specifically, our hydrogel demonstrates a maximum toughness of 20.3 MJ/m3 and a strain of 4079%, an accomplishment rarely observed in other adhesive hydrogel. Furthermore, the hydrogel's adhesion is both reversible and versatile, adhering effectively to a variety of wet and dry substrates. This makes it a promising candidate for advanced healthcare applications, particularly as a mechanically reinforced underwater adhesive with unparalleled stability. We also provide insights into the role of LiCl in the hydrogel matrix, emphasizing its influence on electrostatic interactions without affecting the hydrogen bonds. This study serves as a testament to the potential of harmonizing adhesive and cohesive properties in hydrogels, paving the way for future innovations in the field.

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