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2.
J Tissue Viability ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38886143

RESUMEN

BACKGROUND: The association between underweight and pressure injuries (PIs) has been established in several studies. However, there is a lack of well-designed research investigating the connection between overweight and obesity with these injuries. OBJECTIVE: This meta-analysis aims to investigate the dose-response relationship between body mass index (BMI) and the risk of PIs in adult hospitalized patients. METHODS: PubMed, Web of Science, and MEDLINE Databases were searched from inception to May 2024. Observational articles with at least three BMI categories were included in the study. BMI was defined as underweight, normal weight, overweight, and morbid obesity for the meta-analysis. The non-linear relationship between BMI and the risk of PIs in hospitalized adults was investigated using restricted cubic spline models. Fractional polynomial modeling was used. RESULTS: Eleven articles reporting at least 3 categories of BMI met the inclusion criteria, including 31,389 participants. Compared to patients with normal weight, those with underweight, obesity, and morbid obesity exhibited an increased risk of PIs, with odds ratios of 1.70 (95%CI:1.50-1.91), 1.12 (95%CI:1.02-1.24), 1.70 (95%CI:1.13-2.55), respectively. A J-shaped dose-response model was established for the relationship between PI risk and BMI (Pnon-linearity < 0.001, Plinearity = 0.745). CONCLUSION: The J-shaped dose-response pattern revealed that underweight, obesity and morbid obesity heightened the risk of PIs in hospitalized adults. Lower and higher BMI values may signify an increased risk for PIs, particularly among the elderly with lower BMI, providing valuable guidance for medical staff.

4.
Brain Behav ; 14(7): e3610, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38945806

RESUMEN

INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.


Asunto(s)
Anestésicos por Inhalación , Disfunción Cognitiva , Hipocampo , Isoflurano , Enfermedades Neuroinflamatorias , Efectos Tardíos de la Exposición Prenatal , Privación de Sueño , Animales , Isoflurano/efectos adversos , Isoflurano/farmacología , Isoflurano/administración & dosificación , Femenino , Disfunción Cognitiva/etiología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/fisiopatología , Embarazo , Privación de Sueño/complicaciones , Privación de Sueño/fisiopatología , Ratones , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Anestésicos por Inhalación/efectos adversos , Anestésicos por Inhalación/farmacología , Anestésicos por Inhalación/administración & dosificación , Sinapsis/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Privación Materna , Factor Neurotrófico Derivado del Encéfalo/metabolismo
5.
ChemSusChem ; : e202401120, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935513

RESUMEN

Lithium-rich manganese-based layered oxide cathode materials (LLOs) have always been considered as the most promising cathode materials for achieving high energy density lithium-ion batteries (LIB). However, LLOs often face some key problems, such as low initial coulombic efficiency, capacity/voltage decay, poor rate performance and poor cycle stability. It seriously shortens the lifespan of lithium-ion batteries and hinder the large-scale commercial application of LLOs. Herein, firstly, the basic theories of LLOs were systematically reviewed, including the structural characteristics, the working mechanism of LLOs, the preparation methods of LLOs (liquid phase co-precipitate method, sol-gel method, hydrothermal synthesis method, solid phase method, low heat solid phase method etc,.), and electrochemical characteristics of LLOs (first charge discharge characteristics and reversible efficiency, cycling performance, high and low temperature performance and thermal stability etc,.). Then, key challenges faced by LLOs were systematically discussed. Finally, the LLOs modification strategies used to address these challenges (element doping, surface modification, defect engineering, structural and morphological control etc,.) were elaborated in detail. This important review provides potential insights and directions for further improving  electrochemical performance of LLOs, and provides  necessary theoretical basis for accelerating the large-scale commercial application of LLOs. It possesses important scientific research value and far-reaching social significance.

6.
Int J Mol Med ; 54(1)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38757359

RESUMEN

Following the publication of the above paper, it has been drawn to the Editors' attention by a concerned reader that certain of the lumen formation assay data shown in Fig. 5A on p. 112 were strikingly similar to data appearing in different form in another article written by different authors at different research institute, which had already been published in the journal Biomedicine & Pharmacotherapy prior to the submission of this paper to International Journal of Molecular Medicine, and which has also subsequently been retracted. In view of the fact that the contentious data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 103­114, 2019; DOI: 10.3892/ijmm.2019.4183].

7.
Org Lett ; 26(18): 3982-3986, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38690829

RESUMEN

Described herein is the development of a visible-light-induced photoredox 1,6-enyne reductive cyclization via selective reduction of a triple bond instead of an activated double bond. The selective 1,6-enyne radical cyclization/carbon═carbon double bond cleavage provided a straightforward route to structurally valuable α,ß-unsaturated γ-lactams. TEMPO-trap experiments, control experiments, and DFT calculations have offered evidence supporting the possible catalytic cycle.

8.
Curr Pharm Des ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38798216

RESUMEN

MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges.

9.
Chin Med Sci J ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38594814

RESUMEN

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome (IBS) with a systematic review and meta-analysis. Methods We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, and IEEE Xplore databases until September 2023. Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified. We estimated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with a 95% confidence interval (CI), and plotted a summary receiver operating characteristic curve and evaluated the area under the curve. Results Four studies were included. The pooled diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.94 (95% CI, 0.87-0.97), 0.89 (95% CI, 0.81-0.94), 8.43 (95% CI, 4.81-14.78), 0.07 (95% CI, 0.03-0.15), and 118.86 (95% CI, 44.18-319.75), respectively, with an area under the curve of 0.97 (95% CI, 0.95-0.98). Conclusions Computerized bowel sound analysis is a promising tool for IBS. However, limited high-quality data make the results' validity and applicability questionable. There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis.

10.
ACS Biomater Sci Eng ; 10(5): 2925-2934, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38587986

RESUMEN

Spider dragline (major ampullate) silk is one of the toughest known fibers in nature and exhibits an excellent combination of high tensile strength and elasticity. Increasing evidence has indicated that preassembly plays a crucial role in facilitating the proper assembly of silk fibers by bridging the mesoscale gap between spidroin molecules and the final strong fibers. However, it remains challenging to control the preassembly of spidroins and investigate its influence on fiber structural and mechanical properties. In this study, we explored to bridge this gap by modulating the polyalanine (polyA) motifs in repetitive region of spidroins to tune their preassemblies in aqueous dope solutions. Three biomimetic silk proteins with varying numbers of alanine residues in polyA motif and comparable molecular weights were designed and biosynthesized, termed as N16C-5A, N15C-8A, and N13C-12A, respectively. It was found that all three proteins could form nanofibril assemblies in the concentrated aqueous dopes, but the size and structural stability of the fibrils were distinct from each other. The silk protein N15C-8A with 8 alanine residues in polyA motif allowed for the formation of stable nanofibril assemblies with a length of approximately 200 nm, which were not prone to disassemble or aggregate as that of N16C-5A and N13C-12A. More interestingly, the stable fibril assembly of N15C-8A enabled spinning of simultaneously strong (623.3 MPa) and tough (107.1 MJ m-3) synthetic fibers with fine molecular orientation and close interface packing of fibril bundles. This work highlights that modulation of polyA motifs is a feasible way to tune the morphology and stability of the spidroin preassemblies in dope solutions, thus controlling the structural and mechanical properties of the resulting fibers.


Asunto(s)
Fibroínas , Péptidos , Animales , Secuencias de Aminoácidos , Fibroínas/química , Fibroínas/genética , Nanofibras/química , Péptidos/química , Seda/química , Arañas/química , Resistencia a la Tracción
11.
Fitoterapia ; 176: 105981, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38685513

RESUMEN

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 µM, respectively.


Asunto(s)
Óxido Nítrico , Ácido Oleanólico , Paeonia , Fitoquímicos , Raíces de Plantas , Raíces de Plantas/química , Paeonia/química , Ratones , Animales , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/química , Células RAW 264.7 , Estructura Molecular , Óxido Nítrico/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/química , China , Macrófagos/efectos de los fármacos
12.
Curr Microbiol ; 81(6): 138, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609554

RESUMEN

A Gram-stain-negative bacterium with a rod-to-ovoid shape, named strain M216T, was isolated from sand sediment from the coastal intertidal zone of Huludao, Liaoning Province, China. Growth was observed at 8-40 °C (optimal, 30 °C), pH 5.5-9.5 (optimal, pH 6.5) and 0.5-14.0% (w/v) NaCl (optimal, 6%). Strain M216T possessed ubiquinone-9 as its sole respiratory quinone and phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophosphoglycolipid, one unidentified aminophospholipid, two unidentified phosphoglycolipids, three unidentified phospholipids and three unidentified glycolipids as the main polar lipids. C12:0, C16:0, C12:0 3-OH, C16:1 ω9c, C18:1 ω9c and summed features 3 (C16:1 ω7c and/or C16:1 ω6c) were the major fatty acids (> 5%). The 16S rRNA gene sequence of strain M216T exhibited high similarity to those of 'Marinobacter arenosus' CAU 1620T and Marinobacter adhaerens HP15T (99.3% and 98.5%, respectively) and less than 98.5% similarity to those of the other type strains. The ANI and dDDH values between the strain M216T and 'Marinobacter arenosus' CAU 1620T were 87.4% and 33.3%, respectively; these values were the highest among the other type strains but lower than the species threshold. The G+C content of strain M216T was 58.3%. Genomic analysis revealed that strain M216T harbors the major CAZymes of GH13, GH23, GH73, and PL5, which are responsible for polysaccharide degradation and the potential ability to reduce nitrate to ammonia. Through phenotypic, genotypic, and chemotaxonomic analyses, we proposed the name Marinobacter albus sp. nov., a novel species in the genus Marinobacter, with its type strain M216T (= MCCC 1K08600T = KCTC 82894T).


Asunto(s)
Marinobacter , Marinobacter/genética , ARN Ribosómico 16S/genética , Arena , Amoníaco , China
13.
Cerebellum ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38558026

RESUMEN

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

14.
JACS Au ; 4(4): 1480-1488, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38665676

RESUMEN

Biomolecular condensates are dynamic subcellular compartments that lack surrounding membranes and can spatiotemporally organize the cellular biochemistry of eukaryotic cells. However, such dynamic organization has not been realized in prokaryotes that naturally lack organelles, and strategies are urgently needed for dynamic biomolecular compartmentalization. Here we develop a light-switchable condensate system for on-demand dynamic organization of functional cargoes in the model prokaryotic Escherichia coli cells. The condensate system consists of two modularly designed and genetically encoded fusions that contain a condensation-enabling scaffold and a functional cargo fused to the blue light-responsive heterodimerization pair, iLID and SspB, respectively. By appropriately controlling the biogenesis of the protein fusions, the condensate system allows rapid recruitment and release of cargo proteins within seconds in response to light, and this process is also reversible and repeatable. Finally, the system is demonstrated to dynamically control the subcellular localization of a cell division inhibitor, SulA, which enables the reversible regulation of cell morphologies. Therefore, this study provides a new strategy to dynamically control cellular processes by harnessing light-controlled condensates in prokaryotic cells.

15.
Genome Biol Evol ; 16(3)2024 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-38447062

RESUMEN

Bolboschoenus planiculmis (F.Schmidt) T.V.Egorova is a typical wetland plant in the species-rich Cyperaceae family. This species contributes prominently to carbon dynamics and trophic integration in wetland ecosystems. Previous studies have reported that the chromosomes of B. planiculmis are holocentric; i.e. they have kinetic activity along their entire length and carry multiple centromeres. This feature was suggested to lead to a rapid genome evolution through chromosomal fissions and fusions and participate to the diversification and ecological success of the Bolboschoenus genus. However, the specific mechanism remains uncertain, partly due to the scarcity of genetic information on Bolboschoenus. We present here the first chromosome-level genome assembly for B. planiculmis. Through the integration of high-quality long-read and short-read data, together with chromatin conformation using Hi-C technology, the ultimate genome assembly was 238.01 Mb with a contig N50 value of 3.61 Mb. Repetitive elements constituted 37.04% of the genome, and 18,760 protein-coding genes were predicted. The low proportion of long terminal repeat retrotransposons (∼9.62%) was similar to that reported for other Cyperaceae species. The Ks (synonymous substitutions per synonymous site) distribution suggested no recent large-scale genome duplication in this genome. The haploid assembly contained a large number of 54 pseudochromosomes with a small mean size of 4.10 Mb, covering most of the karyotype. The results of centromere detection support that not all the chromosomes in B. planiculmis have multiple centromeres, indicating more efforts are needed to fully reveal the specific style of holocentricity in cyperids and its evolutionary significance.


Asunto(s)
Cyperaceae , Ecosistema , Cromosomas , Centrómero/genética , Cariotipo , Cromatina , Cyperaceae/genética , Filogenia
16.
AIDS ; 38(8): 1216-1227, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38499478

RESUMEN

OBJECTIVE: Children and adolescents with HIV infection are well known to face a heightened risk of tuberculosis. However, the exact mortality rates and temporal trends of those with HIV-tuberculosis (TB) co-infection remain unclear. We aimed to identify the overall mortality and temporal trends within this population. METHODS: PubMed, Web of Science, and Embase were employed to search for publications reporting on the mortality rates of children and adolescents with HIV-TB co-infection from inception to March 2, 2024. The outcome is the mortality rate for children and adolescents with HIV-TB co-infection during the follow-up period. In addition, we evaluate the temporal trends of mortality. RESULTS: During the follow-up period, the pooled mortality was 16% [95% confidence interval (CI) 13-20]. Single infection of either HIV or TB exhibit lower mortality rates (6% and 4%, respectively). We observed elevated mortality risks among individuals aged less than 12 months, those with extrapulmonary TB, poor adherence to ART, and severe immunosuppression. In addition, we observed a decreasing trend in mortality before 2008 and an increasing trend after 2008, although the trends were not statistically significant ( P  = 0.08 and 0.2 respectively). CONCLUSIONS: Children and adolescents with HIV-TB co-infection bear a significant burden of mortality. Timely screening, effective treatment, and a comprehensive follow-up system contribute to reducing the mortality burden in this population.


Asunto(s)
Coinfección , Infecciones por VIH , Tuberculosis , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Coinfección/mortalidad , Adolescente , Tuberculosis/mortalidad , Tuberculosis/complicaciones , Niño , Preescolar , Lactante , Masculino , Femenino , Análisis de Supervivencia
17.
J Org Chem ; 89(7): 5060-5068, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38525894

RESUMEN

Radical cyclization has been demonstrated to be an efficient method to access functionalized heterocycles from easily accessible raw materials. Described herein is the development of a photocatalytic proton-coupled electron transfer (PCET) strategy for the synthesis of isoquinoline-1,3-diones using readily prepared naphthalimide (NI)-based organic photocatalysts. The process features free metal-complex photocatalysts, acids, and mild reaction conditions. This mild radical cyclization protocol has a broad substrate scope and can be effectively applied to a variety of medicinally relevant substrates. Furthermore, control experiments were conducted to elucidate the mechanism of this visible light-induced methodology.

18.
Acta Pharmacol Sin ; 45(7): 1349-1365, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38504011

RESUMEN

Ischemic stroke is a major cause of disability and death worldwide, and its management requires urgent attention. Previous studies have shown that vagus nerve stimulation (VNS) exerts neuroprotection in ischemic stroke by inhibiting neuroinflammation and apoptosis. In this study, we evaluated the timing for VNS intervention in ischemic stroke, and the underlying mechanisms  of VNS-induced neuroprotection. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. The left vagus nerve at cervical level was exposed and attached to an electrode connected to a low-frequency electrical stimulator. Vagus nerve stimulation (VNS) was given for 60 min before, during and after tMCAO (Pre-VNS, Dur-VNS, Post-VNS). Neurological function was assessed 24 h after reperfusion. We found that all the three VNS significantly protected against the tMCAO-induced injury evidenced by improved neurological function and reduced infarct volume. Moreover, the Pre-VNS was the most effective against the ischemic injury. We found that tMCAO activated microglia in the ischemic core and penumbra regions of the brain, followed by the NLRP3 inflammasome activation-induced neuroinflammation, which finally triggered neuronal death. VNS treatment preserved α7nAChR expression in the penumbra regions, inhibited NLRP3 inflammasome activation and ensuing neuroinflammation, rescuing cerebral neurons. The role of α7nAChR in microglial NLRP3 inflammasome activation in ischemic stroke was further validated using genetic manipulations, including Chrna7 knockout mice and microglial Chrna7 overexpression mice, as well as pharmacological interventions using the α7nAChR inhibitor methyllycaconitine and agonist PNU-282987. Collectively, this study demonstrates the potential of VNS as a safe and effective strategy to treat ischemic stroke, and presents a new approach targeting microglial NLRP3 inflammasome, which might be therapeutic for other inflammation-related diseases.


Asunto(s)
Infarto de la Arteria Cerebral Media , Inflamasomas , Accidente Cerebrovascular Isquémico , Ratones Endogámicos C57BL , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Estimulación del Nervio Vago , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estimulación del Nervio Vago/métodos , Accidente Cerebrovascular Isquémico/metabolismo , Microglía/metabolismo , Ratones , Inflamasomas/metabolismo , Masculino , Infarto de la Arteria Cerebral Media/terapia , Neuroprotección , Ratones Noqueados
19.
Hum Genet ; 143(3): 331-342, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38478153

RESUMEN

Accurate discrimination of pathogenic and nonpathogenic variation remains an enormous challenge in clinical genetic testing of inherited retinal diseases (IRDs) patients. Computational methods for predicting variant pathogenicity are the main solutions for this dilemma. The majority of the state-of-the-art variant pathogenicity prediction tools disregard the differences in characteristics among different genes and treat all types of mutations equally. Since missense variants are the most common type of variation in the coding region of the human genome, we developed a novel missense mutation pathogenicity prediction tool, named Prediction of Deleterious Missense Mutation for IRDs (PdmIRD) in this study. PdmIRD was tailored for IRDs-related genes and constructed with the conditional random forest model. Population frequencies and a newly available prediction tool were incorporated into PdmIRD to improve the performance of the model. The evaluation of PdmIRD demonstrated its superior performance over nonspecific tools (areas under the curves, 0.984 and 0.910) and an existing eye abnormalities-specific tool (areas under the curves, 0.975 and 0.891). We also demonstrated the submodel that used a smaller gene panel further slightly improved performance. Our study provides evidence that a disease-specific model can enhance the prediction of missense mutation pathogenicity, especially when new and important features are considered. Additionally, this study provides guidance for exploring the characteristics and functions of the mutated proteins in a greater number of Mendelian disorders.


Asunto(s)
Mutación Missense , Enfermedades de la Retina , Humanos , Biología Computacional/métodos , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética
20.
Sci Data ; 11(1): 286, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461307

RESUMEN

The progress of aquaculture heavily depends on the efficient utilization of diverse genetic resources to enhance production efficiency and maximize profitability. Single nucleotide polymorphisms (SNPs) have been widely used in the study of aquaculture genomics, genetics, and breeding research since they are the most prevalent molecular markers on the genome. Currently, a large number of SNP markers from cultured fish species are scattered in individual studies, making querying complicated and data reuse problematic. We compiled relevant SNP data from literature and public databases to create a fish SNP database, FishSNP ( http://bioinfo.ihb.ac.cn/fishsnp ), and also used a unified analysis pipeline to process raw data that the author of the literature did not perform SNP calling on to obtain SNPs with high reliability. This database presently contains 45,690,243 (45 million) nonredundant SNP data for 13 fish species, with 30,288,958 (30 million) of those being high-quality SNPs. The main function of FishSNP is to search, browse, annotate and download SNPs, which provide researchers various and comprehensive associated information.


Asunto(s)
Bases de Datos Genéticas , Peces , Genómica , Polimorfismo de Nucleótido Simple , Animales , Peces/genética , Genoma , Reproducibilidad de los Resultados
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