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1.
Bioinformatics ; 40(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38547405

RESUMEN

MOTIVATION: Protein sequence database search and multiple sequence alignment generation is a fundamental task in many bioinformatics analyses. As the data volume of sequences continues to grow rapidly, there is an increasing need for efficient and scalable multiple sequence query algorithms for super-large databases without expensive time and computational costs. RESULTS: We introduce Chorus, a novel protein sequence query system that leverages parallel model and heterogeneous computation architecture to enable users to query thousands of protein sequences concurrently against large protein databases on a desktop workstation. Chorus achieves over 100× speedup over BLASTP without sacrificing sensitivity. We demonstrate the utility of Chorus through a case study of analyzing a ∼1.5-TB large-scale metagenomic datasets for novel CRISPR-Cas protein discovery within 30 min. AVAILABILITY AND IMPLEMENTATION: Chorus is open-source and its code repository is available at https://github.com/Bio-Acc/Chorus.


Asunto(s)
Algoritmos , Programas Informáticos , Secuencia de Aminoácidos , Proteínas , Bases de Datos de Proteínas
2.
J Am Chem Soc ; 146(22): 15576-15586, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38753821

RESUMEN

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

3.
Neurobiol Dis ; 197: 106534, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759931

RESUMEN

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.


Asunto(s)
Esclerosis Amiotrófica Lateral , Modelos Animales de Enfermedad , Ratones Transgénicos , Proteínas Mitocondriales , Mitofagia , Neuronas Motoras , Animales , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/genética , Mitofagia/fisiología , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Ratones , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Humanos , Médula Espinal/metabolismo , Médula Espinal/patología
4.
BMC Vet Res ; 20(1): 295, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971753

RESUMEN

BACKGROUND: Fatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows. RESULTS: A total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows. CONCLUSIONS: Our data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.


Asunto(s)
Enfermedades de los Bovinos , Hígado Graso , Periodo Periparto , Animales , Bovinos/sangre , Femenino , Enfermedades de los Bovinos/sangre , Enfermedades de los Bovinos/diagnóstico , Hígado Graso/veterinaria , Hígado Graso/sangre , Hígado Graso/diagnóstico , Periodo Periparto/sangre , Biomarcadores/sangre , Manganeso/sangre , Oligoelementos/sangre , Molibdeno/sangre , Hígado/química , Potasio/sangre , Boro/sangre , Selenio/sangre , Calcio/sangre , Magnesio/sangre , Embarazo
5.
Molecules ; 29(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38611882

RESUMEN

This study evaluated the impact of pulsed electric fields (PEFs) combined with three-phase partitioning (TPP) extraction methods on the physicochemical properties, functional properties, and structural characterization of the soluble dietary fiber (SDF) derived from peanut shells (PS). The findings of this study indicated that the application of a PEF-TPP treatment leads to a notable improvement in both the extraction yield and purity of SDF. Consequently, the PEF-TPP treatment resulted in the formation of more intricate and permeable structures, a decrease in molecular weight, and an increase in thermal stability compared to SDFs without TPP treatment. An analysis revealed that the PEF-TPP method resulted in an increase in the levels of arabinose and galacturonic acid, leading to enhanced antioxidant capacities. Specifically, the IC50 values were lower in SDFs which underwent PEF-TPP (4.42 for DPPH and 5.07 mg/mL for ABTS) compared to those precipitated with 40% alcohol (5.54 mg/mL for DPPH, 5.56 mg/mL for ABTS) and PEF75 (6.60 mg/mL for DPPH, 7.61 mg/mL for ABTS), respectively. Notably, the SDFs which underwent PEF-TPP demonstrated the highest water- and oil-holding capacity, swelling capacity, emulsifying activity, emulsion stability, glucose adsorption, pancreatic lipase inhibition, cholesterol adsorption, nitric ion adsorption capacity, and the least gelation concentration. Based on the synthesis scores obtained through PCA (0.536 > -0.030 > -0.33), which indicated that SDFs which underwent PEF-TPP exhibited the highest level of quality, the findings indicate that PEF-TPP exhibits potential and promise as a method for preparing SDFs.


Asunto(s)
Antioxidantes , Arachis , Benzotiazoles , Ácidos Sulfónicos , Adsorción , Fibras de la Dieta
6.
Compr Rev Food Sci Food Saf ; 23(2): e13311, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38445543

RESUMEN

ß-Casein, an important protein found in bovine milk, has significant potential for application in the food, pharmaceutical, and other related industries. This review first introduces the composition, structure, and functional properties of ß-casein. It then reviews the techniques for isolating ß-casein. Chemical and enzymatic isolation methods result in inactivity of ß-casein and other components in the milk, and it is difficult to control the production conditions, limiting the utilization range of products. Physical technology not only achieves high product purity and activity but also effectively preserves the biological activity of the components. The isolated ß-casein needs to be utilized effectively and efficiently for various purity products in order to achieve optimal targeted application. Bovine ß-casein, which has a purity higher than or close to that of breast ß-casein, can be used in infant formulas. This is achieved by modifying its structure through dephosphorylation, resulting in a formula that closely mimics the composition of breast milk. Bovine ß-casein, which is lower in purity than breast ß-casein, can be maximized for the preparation of functional peptides and for use as natural carriers. The remaining byproducts can be utilized as food ingredients, emulsifiers, and carriers for encapsulating and delivering active substances. Thus, realizing the intensive processing and utilization of bovine ß-casein isolation. This review can promote the industrial production process of ß-casein, which is beneficial for the sustainable development of ß-casein as a food and material. It also provides valuable insights for the development of other active substances in milk.


Asunto(s)
Ingredientes Alimentarios , Leche , Humanos , Femenino , Lactante , Animales , Caseínas , Emulsionantes , Fórmulas Infantiles
7.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2871-2881, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-39041146

RESUMEN

To investigate the effects of different ratios of organic and chemical fertilizers on the yield and quality of Epimedium pubescens,so as to provide a scientific basis for the fertilization of high-yield and high-quality E. pubescens cultivation. In this experiment,a field plot test was conducted,and CK(without fertilizer) was set as the control group,with five treatment groups with different ratios of organic fertilizers and chemical fertilizers set up,namely OF0(100% chemical fertilizers),OF25(25% organic fertilizers),OF50(50% organic fertilizers),OF75(75% organic fertilizers),and OF100(100% organic fertilizers). The effects of different fertilization patterns on the agronomic traits,yield,effective component content,nutrient accumulation,and soil physicochemical properties of E. pubescens were determined,and the yield and quality of the medicinal herb were comprehensively evaluated by using the CRITIC weights method. It was found that the herb yield of each treatment group was significantly increased compared with the CK group,although the yield of the groups with both organic fertilizer and chemical fertilizer was slightly lower than that of OF0. However,there was no significant difference,which indicated that the organic fertilizer combined with chemical fertilizer could ensure the herb yield. With the increase in organic fertilizer ratios,the medicinal components epimedin A,epimedin B,and epimedin C showed a tendency of first increasing and then decreasing,with the highest content in the OF25,while icariin showed a rising trend,with the best in the OF100. However,overall,the total flavonol glycosides ABCI accumulated the most in the OF25. The results of the CRITIC method showed that the top three fertilization treatments in terms of the comprehensive scores of the medicinal herb were OF25,OF50,and OF75. Organic fertilizer combined with chemical fertilizer is conducive to improving the soil's fertilizer holding and supply capacity,and the soil indexes are optimal in OF100. The soil enzyme activity is the highest in OF75. Meanwhile,organic fertilizer combined with chemical fertilizer can help the plant's uptake and accumulation of nutrients,and OF25 shows the most obvious effect.By comprehensively considering the influence of different ratios of organic and chemical fertilizers on the yield,effective component content,nutrient accumulation,and other indexes of E. pubescens,it is recommended that a 25% ratio(7 500 kg·hm~(-2)) of organic fertilizers and chemical fertilizers should be used in E. pubescens production in the first year,so as to promote the E. pubescens industry to increase yield and improve quality.


Asunto(s)
Epimedium , Fertilizantes , Fertilizantes/análisis , Epimedium/química , Epimedium/crecimiento & desarrollo , Suelo/química , Nitrógeno/metabolismo , Nitrógeno/análisis , Control de Calidad
8.
Angew Chem Int Ed Engl ; 63(10): e202318803, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38205884

RESUMEN

Transition metal-catalyzed enantioselective C-H carbonylation with carbon monoxide, an essential and easily available C1 feedstock, remains challenging. Here, we disclosed an unprecedented enantioselective C-H carbonylation catalyzed by inexpensive and readily available cobalt(II) salt. The reactions proceed efficiently through desymmetrization, kinetic resolution, and parallel kinetic resolution, affording a broad range of chiral isoindolinones in good yields with excellent enantioselectivities (up to 92 % yield and 99 % ee). The synthetic potential of this method was demonstrated by asymmetric synthesis of biological active compounds, such as (S)-PD172938 and (S)-Pazinaclone. The resulting chiral isoindolinones also serve as chiral ligands in cobalt-catalyzed enantioselective C-H annulation with alkynes to construct phosphorus stereocenter.

9.
Angew Chem Int Ed Engl ; : e202407640, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898602

RESUMEN

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C-H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C-H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96 % to >99 % ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step.

10.
J Am Chem Soc ; 145(45): 24499-24505, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38104268

RESUMEN

The transition metal-catalyzed enantioselective C-H functionalization strategy has revolutionized the logic of natural product synthesis. However, previous applications have heavily relied on the use of noble metal catalysts such as rhodium and palladium. Herein, we report the efficient synthesis of C1-chiral 1,2-dihydroisoquinolines (DHIQs) via enantioselective C-H/N-H annulation of picolinamides with alkynes catalyzed by a more sustainable and cheaper 3d metal catalyst, cobalt(II) acetate tetrahydrate. A wide range of enantiomerically enriched DHIQs were obtained in good yields with excellent enantioselectivities (up to 98% yield and >99% ee). The robustness and synthetic potential of this method were demonstrated by the modular and asymmetric syntheses of several tetrahydroisoquinoline alkaloids, including (S)-norlaudanosine, (S)-laudanosine, (S)-xylopinine, (S)-sebiferine, and (S)-cryptostyline II, and the asymmetric syntheses of key intermediates of (+)-solifenacin, FR115427, and (+)-NPS R-568.

11.
Oncol Lett ; 27(3): 121, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38348385

RESUMEN

Multiple primary intracranial tumors, or the presence of two or more primary intracranial tumors, are a rare clinical occurrence. The current study presents the case of a 28-year-old patient with concurrent left vestibular schwannoma, left cerebellar hemisphere dermoid cyst and craniovertebral junction malformation, specifically basilar invagination and Klippel-Feil syndrome. The patient exhibited symptoms of torticollis and recurrent headaches, with no apparent hearing loss. A far lateral approach was selected for surgical resection to address these complex conditions and achieve gross total resection in a single-stage surgery while preserving both facial and auditory nerve function. Successful gross total resection was achieved and the function of both nerves was effectively preserved. Of note, the coexistence of vestibular schwannoma and dermoid cyst in the same patient has not been documented in the existing literature. The present study provided a comprehensive account of the presentation and progression of this uncommon medical scenario. Furthermore, a surgical principle for the management of multiple primary intracranial tumors was proposed.

12.
Heliyon ; 10(14): e34519, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39113997

RESUMEN

Background: Fibroblasts play an important role in the development of idiopathic pulmonary fibrosis (IPF). Methods: We employed single-cell RNA-sequencing data obtained from the Gene Expression Omnibus database to perform cell clustering and annotation analyses. We then performed secondary clustering of fibroblasts and conducted functional enrichment and cell trajectory analyses of the two newly defined fibroblast subtypes. Bulk RNA-sequencing data were used to perform consensus clustering and weighted gene co-expression network analysis. We constructed a fibroblast-related prognostic model using least absolute shrinkage, selection operator regression, and Cox regression analysis. The prognostic model was validated using a validation dataset. Immune infiltration and functional enrichment analyses were conducted for patients in the high- and low-risk IPF groups. Results: We characterized two fibroblast subtypes that are active in IPF (F3+ and ROBO2+). Using fibroblast-related genes, we identified five genes (CXCL14, TM4SF1, CYTL1, SOD3, and MMP10) for the prognostic model. The area under the curve values of our prognostic model were 0.852, 0.859, and 0.844 at one, two, and three years in the training set, and 0.837, 0.758, and 0.821 at one, two, and three years in the validation set, respectively. Conclusion: This study annotates and characterizes different subtypes of fibroblasts in IPF.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38917280

RESUMEN

Multimodal aspect-based sentiment classification (MABSC) aims to identify the sentiment polarity toward specific aspects in multimodal data. It has gained significant attention with the increasing use of social media platforms. Existing approaches primarily focus on analyzing the content of posts to predict sentiment. However, they often struggle with limited contextual information inherent in social media posts, hindering accurate sentiment detection. To overcome this issue, we propose a novel multimodal dual cause analysis (MDCA) method to track the underlying causes behind expressed sentiments. MDCA can provide additional reasoning cause (RC) and direct cause (DC) to explain why users express certain emotions, thus helping improve the accuracy of sentiment prediction. To develop a model with MDCA, we construct MABSC datasets with RC and DC by utilizing large language models (LLMs) and visual-language models. Subsequently, we devise a multitask learning framework that leverages the datasets with cause data to train a small generative model, which can generate RC and DC, and predict the sentiment assisted by these causes. Experimental results on MABSC benchmark datasets demonstrate that our MDCA model achieves the state-of-the-art performance, and the small fine-tuned model exhibits superior adaptability to MABSC compared to large models like ChatGPT and BLIP-2.

14.
J Cardiothorac Surg ; 19(1): 362, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915077

RESUMEN

BACKGROUND: Acute type A aortic dissection is a dangerous disease that threatens public health. In recent years, with the progress of medical technology, the mortality rate of patients after surgery has been gradually reduced, leading that previous prediction models may not be suitable for nowadays. Therefore, the present study aims to find new independent risk factors for predicting in-hospital mortality and construct a nomogram prediction model. METHODS: The clinical data of 341 consecutive patients in our center from 2019 to 2023 were collected, and they were divided into two groups according to the death during hospitalization. The independent risk factors were analyzed by univariate and multivariate logistic regression, and the nomogram was constructed and verified based on these factors. RESULTS: age, preoperative lower limb ischemia, preoperative activated partial thromboplastin time (APTT), preoperative platelet count, Cardiopulmonary bypass (CPB) time and postoperative acute kidney injury (AKI) independently predicted in-hospital mortality of patients with acute type A aortic dissection after surgery. The area under the receiver operating characteristic curve (AUC) for the nomogram was 0.844. The calibration curve and decision curve analysis verified that the model had good quality. CONCLUSION: The new nomogram model has a good ability to predict the in-hospital mortality of patients with acute type A aortic dissection after surgery.


Asunto(s)
Disección Aórtica , Mortalidad Hospitalaria , Nomogramas , Humanos , Disección Aórtica/cirugía , Disección Aórtica/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Anciano , Complicaciones Posoperatorias/mortalidad , Enfermedad Aguda , Curva ROC , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta/cirugía , Aneurisma de la Aorta/mortalidad , Medición de Riesgo/métodos
15.
Biomolecules ; 14(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38927095

RESUMEN

As an essential component of modern drug discovery, the role of drug-target identification is growing increasingly prominent. Additionally, single-omics technologies have been widely utilized in the process of discovering drug targets. However, it is difficult for any single-omics level to clearly expound the causal connection between drugs and how they give rise to the emergence of complex phenotypes. With the progress of large-scale sequencing and the development of high-throughput technologies, the tendency in drug-target identification has shifted towards integrated multi-omics techniques, gradually replacing traditional single-omics techniques. Herein, this review centers on the recent advancements in the domain of integrated multi-omics techniques for target identification, highlights the common multi-omics analysis strategies, briefly summarizes the selection of multi-omics analysis tools, and explores the challenges of existing multi-omics analyses, as well as the applications of multi-omics technology in drug-target identification.


Asunto(s)
Descubrimiento de Drogas , Genómica , Proteómica , Humanos , Genómica/métodos , Descubrimiento de Drogas/métodos , Proteómica/métodos , Metabolómica/métodos , Biología Computacional/métodos , Multiómica
16.
Front Immunol ; 15: 1393801, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660302

RESUMEN

Background: Human tumors pose significant challenges, with targeted therapy against specific molecular targets or signaling pathways being a mainstay alongside surgical resection. Previous studies have implicated KHDRBS1 in the oncogenesis of certain human tumors such as colorectal and prostate cancers, underscoring its potential as a therapeutic target. However, the comprehensive expression pattern of KHDRBS1 in hepatocellular carcinoma (HCC) warrants further exploration. Methods: Integrating and analyzing multi-omics, multi-cohort data from public databases, coupled with clinical samples and molecular biology validation, we elucidate the oncogenic role of KHDRBS1 in HCC progression. Additionally, leveraging HCC single-cell sequencing data, we segregate malignant cells into KHDRBS1-positive and negative subsets, uncovering significant differences in their expression profiles and functional roles. Results: Our study identifies KHDRBS1 as a tumor-promoting factor in HCC, with its positivity correlating with tumor progression. Furthermore, we highlight the clinical significance of KHDRBS1-positive malignant cells, aiming to further propel its clinical utility. Conclusion: KHDRBS1 plays a key role in HCC development. This study provides crucial insights for further investigation into KHDRBS1 as a therapeutic target in HCC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Masculino , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Pronóstico , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Transducción de Señal , Microambiente Tumoral/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo
17.
Discov Oncol ; 15(1): 182, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782769

RESUMEN

BACKGROUND: The lncRNA growth arrest-specific 5 (GAS5) is involved in regulating breast cancer progression. In this study, we aimed to elucidate the function and mechanism of GAS5 in breast cancer. METHODS: The expressions of GAS5, fat mass and obesity-associated protein (FTO), insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and Quaking (QKI) were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. The m6A modification level of GAS5 was detected using m6A immunoprecipitation assay (MeRIP). The interaction between IGF2BP2 and GAS5 or QKI was detected using RNA immunoprecipitation assay (RIP) and dual luciferase reporter assay. Cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) assay. The biological functions of the FTO/GAS5/IGF2BP2/QKI axis was assessed using the tumor xenograft assay. RESULTS: LncRNA GAS5 expression decreased in breast cancer and was regulated by FTO-mediated m6A modification in an IGF2BP2-dependent manner, resulting in decreased GAS5 stability and expression. GAS5 recruited IGF2BP2 to target QKI and upregulated QKI expression in breast cancer cells. GAS5 suppressed breast cancer growth via IGF2BP2/QKI, and this inhibitory effect was modulated by FTO both in vitro and in vivo. CONCLUSIONS: GAS5 regulated by FTO-mediated m6A modification represses the growth of breast cancer via the IGF2BP2/QKI pathway, suggesting that the FTO/GAS5/IGF2BP2/QKI pathway can be a potential target for breast cancer treatment.

18.
PLoS One ; 19(7): e0307201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39042642

RESUMEN

With the rapid pace of industrialization and the increasing intensity of human activities, the global climate change and energy crisis have reached a heightened level of severity. Consequently, achieving an early peak in carbon emissions has become an imperative in addressing this pressing issue. Particularly, coastal provinces, known for their developed economies, high population density, and substantial building energy consumption, have emerged as significant contributors to carbon emissions. Notably, public buildings, serving as critical constituents of the construction industry, possess immense potential for both energy conservation and emissions reduction. In light of this, the present study focuses on Fujian Province, situated along the coast, and constructs a carbon emission estimation model for public buildings based on the Kaya identity. This model takes into account various factors specific to Fujian Province, including population characteristics, economic conditions, tertiary industry development, public building area, and energy consumption. Through scenario analysis, the study projects that the year of peak carbon emissions for public buildings in Fujian Province is estimated to be 2030, 2035, and 2040 under low-carbon, baseline, and high-carbon scenarios respectively. The corresponding peak carbon emission levels are anticipated to reach 23.62 million t, 24.18 million t, and 24.76 million t CO2. Lastly, based on local policies and actual conditions, the study proposes a set of policy measures and feasible approaches tailored to Fujian Province, aiming to achieve an early peak in carbon emissions.


Asunto(s)
Carbono , China , Carbono/análisis , Humanos , Dióxido de Carbono/análisis , Cambio Climático , Modelos Teóricos
19.
Front Genet ; 15: 1442277, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39130754

RESUMEN

Introduction: Research on Glycyrrhiza uralensis, a nonhalophyte that thrives in saline-alkaline soil and a traditional Chinese medicinal component, is focused on improving its ability to tolerate salt stress to increase its productivity and preserve its "Dao-di" characteristics. Furthermore, the inoculation of bioagents such as Bacillus subtilis to increase plant responses to abiotic stressors is currently a mainstream strategy. Mitogen-activated protein kinase (MAPK), a highly conserved protein kinase, plays a significant role in plant responses to various abiotic stress pathways. Methods: This investigation involved the identification of 21 members of the GuMAPK family from the genome of G. uralensis, with an analysis of their protein conserved domains, gene structures, evolutionary relationships, and phosphorylation sites using bioinformatics tools. Results: Systematic evolutionary analysis of the 21 GuMAPKs classified them into four distinct subgroups, revealing significant differences in gene structure and exon numbers. Collinearity analysis highlighted the crucial role of segmental duplication in expanding the GuMAPK gene family, which is particularly evident in G. uralensis and shows a close phylogenetic relationship with Arabidopsis thaliana, tomato, and cucumber. Additionally, the identification of phosphorylation sites suggests a strong correlation between GuMAPK and various physiological processes, including hormonal responses, stress resistance, and growth and development. Protein interaction analysis further supported the role of GuMAPK proteins in regulating essential downstream genes. Through examination of transcriptome expression patterns, GuMAPK16-2 emerged as a prospective pivotal regulatory factor in the context of salt stress and B. subtilis inoculation, a finding supported by its subcellular localization within the nucleus. Discussion: These discoveries offer compelling evidence for the involvement of GuMAPK in the salt stress response and for the exploration of the mechanisms underlying B. subtilis' enhancement of salt tolerance in G. uralensis.

20.
Sci Rep ; 14(1): 18114, 2024 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103554

RESUMEN

Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case-control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges-Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges-Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6-8 days; adjusted difference, 8.31 days, 95% CI 7.16-9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54-0.82; adjusted OR 0.75, 95% CI 0.61-0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.


Asunto(s)
Grupos Diagnósticos Relacionados , Tiempo de Internación , Centros de Atención Terciaria , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Adulto , China , Bases de Datos Factuales , Hospitalización/estadística & datos numéricos , Pacientes Internos/estadística & datos numéricos , Costos de Hospital , Adulto Joven
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