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1.
Cell ; 181(6): 1232-1245.e20, 2020 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-32437661

RESUMEN

Modern humans have inhabited the Lake Baikal region since the Upper Paleolithic, though the precise history of its peoples over this long time span is still largely unknown. Here, we report genome-wide data from 19 Upper Paleolithic to Early Bronze Age individuals from this Siberian region. An Upper Paleolithic genome shows a direct link with the First Americans by sharing the admixed ancestry that gave rise to all non-Arctic Native Americans. We also demonstrate the formation of Early Neolithic and Bronze Age Baikal populations as the result of prolonged admixture throughout the eighth to sixth millennium BP. Moreover, we detect genetic interactions with western Eurasian steppe populations and reconstruct Yersinia pestis genomes from two Early Bronze Age individuals without western Eurasian ancestry. Overall, our study demonstrates the most deeply divergent connection between Upper Paleolithic Siberians and the First Americans and reveals human and pathogen mobility across Eurasia during the Bronze Age.


Asunto(s)
Genoma Humano/genética , Migración Humana/historia , Grupos Raciales/genética , Grupos Raciales/historia , Asia , ADN Antiguo , Europa (Continente) , Historia Antigua , Humanos , Siberia
2.
Nature ; 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39478221

RESUMEN

The Caucasus and surrounding areas, with their rich metal resources, became a crucible of the Bronze Age1 and the birthplace of the earliest steppe pastoralist societies2. Yet, despite this region having a large influence on the subsequent development of Europe and Asia, questions remain regarding its hunter-gatherer past and its formation of expansionist mobile steppe societies3-5. Here we present new genome-wide data for 131 individuals from 38 archaeological sites spanning 6,000 years. We find a strong genetic differentiation between populations north and south of the Caucasus mountains during the Mesolithic, with Eastern hunter-gatherer ancestry4,6 in the north, and a distinct Caucasus hunter-gatherer ancestry7 with increasing East Anatolian farmer admixture in the south. During the subsequent Eneolithic period, we observe the formation of the characteristic West Eurasian steppe ancestry and heightened interaction between the mountain and steppe regions, facilitated by technological developments of the Maykop cultural complex8. By contrast, the peak of pastoralist activities and territorial expansions during the Early and Middle Bronze Age is characterized by long-term genetic stability. The Late Bronze Age marks another period of gene flow from multiple distinct sources that coincides with a decline of steppe cultures, followed by a transformation and absorption of the steppe ancestry into highland populations.

3.
Nature ; 615(7950): 117-126, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36859578

RESUMEN

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants.


Asunto(s)
Arqueología , Genoma Humano , Genómica , Genética Humana , Caza , Paleontología , Humanos , Europa (Continente)/etnología , Pool de Genes , Historia Antigua , Genoma Humano/genética
4.
Brief Bioinform ; 25(1)2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-38189542

RESUMEN

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncRNAs play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncRNAs in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncRNA biomarkers and elucidate the underlying mechanisms of ncRNA. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncRNAs in disease and guide a novel approach for early diagnosis and treatment of disease.


Asunto(s)
Errores Innatos del Metabolismo de los Carbohidratos , Diabetes Gestacional , Síndromes de Malabsorción , Humanos , Femenino , Embarazo , Diabetes Gestacional/genética , Genoma Humano , ARN no Traducido/genética , Biomarcadores
5.
J Proteome Res ; 23(10): 4409-4421, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39235835

RESUMEN

N-Glycan-dependent endoplasmic reticulum quality control (ERQC) primarily mediates protein folding, which determines the fate of the polypeptide. Monoglucose residues on N-glycans determine whether the nascent N-glycosylated proteins enter into and escape from the calnexin (CANX)/calreticulin (CALR) cycle, which is a central system of the ERQC. To reveal the impact of ERQC on glycosylation and protein fate, we performed comprehensive quantitative proteomic and glycoproteomic analyses using cells defective in N-glycan-dependent ERQC. Deficiency of MOGS encoding the ER α-glucosidase I, CANX, or/and CALR broadly affected protein expression and glycosylation. Among the altered glycoproteins, the occupancy of oligomannosidic N-glycans was significantly affected. Besides the expected ER stress, proteins and glycoproteins involved in pathways for lysosome and viral infection are differentially changed in those deficient cells. We demonstrated that lysosomal hydrolases were not correctly modified with mannose-6-phosphates on the N-glycans and were directly secreted to the culture medium in N-glycan-dependent ERQC mutant cells. Overall, the CANX/CALR cycle promotes the correct folding of glycosylated peptides and influences the transport of lysosomal hydrolases.


Asunto(s)
Calnexina , Retículo Endoplásmico , Glicoproteínas , Lisosomas , Polisacáridos , Proteoma , alfa-Glucosidasas , Glicosilación , Retículo Endoplásmico/metabolismo , Polisacáridos/metabolismo , Calnexina/metabolismo , Calnexina/genética , Lisosomas/metabolismo , Proteoma/metabolismo , Proteoma/análisis , Glicoproteínas/metabolismo , Glicoproteínas/genética , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/genética , Calreticulina/metabolismo , Calreticulina/genética , Hidrolasas/metabolismo , Hidrolasas/genética , Humanos , Proteómica/métodos , Pliegue de Proteína , Animales
6.
Immunology ; 173(1): 172-184, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38840413

RESUMEN

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and the early detection and diagnosis of this disease are crucial in reducing mortality rates. The timely diagnosis of LUAD is essential for controlling tumour development and enabling early surgical treatment. GPR56 is a vital G protein-coupled receptor and its role in T lymphocytes has received considerable attention. However, its function in B cells remains unclear. This study aimed to investigate the significance of GPR56 in LUAD. We found that GPR56 exhibited a significant increase in circulating plasmablasts and a decrease in new memory B cells. GPR56 expression in B cells was significantly reduced after LPS stimulation and the proportion of HLA-DR+ and CD40+ proportions were also decreased in GPR56+ B cells after stimulation. Additionally, GPR56 exhibited significant down-regulation in circulating B cell subsets of early-stage LUAD patients, and there were significant correlations between GPR56+ B cell subsets and tumour markers. In conclusion, GPR56 could reflect the hypoactivation state of B cells and the decreased proportion of GPR56+ B cell subset in LUAD patients can signify the active humoral immunity in vivo. The expression of GPR56 in B cells could potentially hold value in the early diagnosis of LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Activación de Linfocitos , Regulación hacia Abajo , Estadificación de Neoplasias , Inmunidad Humoral , Biomarcadores de Tumor/metabolismo
7.
J Am Chem Soc ; 146(22): 15473-15478, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38782032

RESUMEN

The synthesis and characterization of a series of polyantimony anionic clusters are reported. The products [(NbCp)2Sb10]2-, [MSb13]3- (M = Ru/Fe), and [MSb15]3- (M = Ru/Fe) were isolated as either K(18-crown-6) or K([2.2.2]-crypt) salts. The Sb10 ring contained in the [(NbCp)2Sb10]2- cluster can be viewed as an extension of two envelope-like cyclo-Sb5 units and represents by far the largest monocyclic all-antimony species. The clusters [MSb13]3- and [MSb15]3- (M = Ru/Fe) illustrate the variability of crown-like Sb8 ring motifs and reveal the fusion of different antimony fragments featuring unique Sb-Sb chain-like units. The reported synthetic approaches involve the fabrication of a variety of distinctive polyantimony anionic clusters, enhancing our understanding of the coordination chemistry of heavier group 15 elements.

8.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36007239

RESUMEN

Recently, many studies have shown that lncRNA can mediate the regulation of TF-gene in drug sensitivity. However, there is still a lack of systematic identification of lncRNA-TF-gene regulatory triplets for drug sensitivity. In this study, we propose a novel analytic approach to systematically identify the lncRNA-TF-gene regulatory triplets related to the drug sensitivity by integrating transcriptome data and drug sensitivity data. Totally, 1570 drug sensitivity-related lncRNA-TF-gene triplets were identified, and 16 307 relationships were formed between drugs and triplets. Then, a comprehensive characterization was performed. Drug sensitivity-related triplets affect a variety of biological functions including drug response-related pathways. Phenotypic similarity analysis showed that the drugs with many shared triplets had high similarity in their two-dimensional structures and indications. In addition, Network analysis revealed the diverse regulation mechanism of lncRNAs in different drugs. Also, survival analysis indicated that lncRNA-TF-gene triplets related to the drug sensitivity could be candidate prognostic biomarkers for clinical applications. Next, using the random walk algorithm, the results of which we screen therapeutic drugs for patients across three cancer types showed high accuracy in the drug-cell line heterogeneity network based on the identified triplets. Besides, we developed a user-friendly web interface-DrugSETs (http://bio-bigdata.hrbmu.edu.cn/DrugSETs/) available to explore 1570 lncRNA-TF-gene triplets relevant with 282 drugs. It can also submit a patient's expression profile to predict therapeutic drugs conveniently. In summary, our research may promote the study of lncRNAs in the drug resistance mechanism and improve the effectiveness of treatment.


Asunto(s)
ARN Largo no Codificante , Biomarcadores , Resistencia a Medicamentos , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
9.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36070864

RESUMEN

The location of microRNAs (miRNAs) in cells determines their function in regulation activity. Studies have shown that miRNAs are stable in the extracellular environment that mediates cell-to-cell communication and are located in the intracellular region that responds to cellular stress and environmental stimuli. Though in situ detection techniques of miRNAs have made great contributions to the study of the localization and distribution of miRNAs, miRNA subcellular localization and their role are still in progress. Recently, some machine learning-based algorithms have been designed for miRNA subcellular location prediction, but their performance is still far from satisfactory. Here, we present a new data partitioning strategy that categorizes functionally similar locations for the precise and instructive prediction of miRNA subcellular location in Homo sapiens. To characterize the localization signals, we adopted one-hot encoding with post padding to represent the whole miRNA sequences, and proposed a deep bidirectional long short-term memory with the multi-head self-attention algorithm to model. The algorithm showed high selectivity in distinguishing extracellular miRNAs from intracellular miRNAs. Moreover, a series of motif analyses were performed to explore the mechanism of miRNA subcellular localization. To improve the convenience of the model, a user-friendly web server named iLoc-miRNA was established (http://iLoc-miRNA.lin-group.cn/).


Asunto(s)
Biología Computacional , MicroARNs , Algoritmos , Biología Computacional/métodos , Humanos , Aprendizaje Automático , MicroARNs/genética
10.
Anal Biochem ; 687: 115430, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38147947

RESUMEN

Fritillaria ussuriensis Maxim is one of the traditional Chinese valuable herbs, which is the dried bulb of Fritillaria, a plant of the lily family. The identification of authenticity about F. ussuriensis is still technically challenging. In this study, visual identification was performed by ring-mediated isothermal amplification and nucleic acid colloidal gold techniques. Firstly, multiple sequence comparative analysis was performed by DNAMAN to find the differential sites of F. ussuriensis and its mixed pseudo-products, and the specific identification primers of F. ussuriensis were designed. Genomic DNA was extracted by the modified CTAB method, and the reaction system and reaction conditions were optimized to construct LAMP for the visual detection of F. ussuriensis, meanwhile, the genuine product was cloned and the extracted plasmid was sequenced. The specificity and sensitivity were detected, and also verified by nucleic acid colloidal gold method, and 20 commercially available samples were tested. The extracted DNA met the requirements of the experiment, and the genuine F. ussuriensis PCR product titrated on a test strip showed two bands on the T and C lines, while the counterfeit and negative control showed only one band on the C line, which matched the LAMP results. The specificity was 100 %, and the sensitivity of LAMP assay was up to 0.01 ng µL-1, while that of colloidal gold assay was 0.1 ng µL-1, thus the LAMP assay had high sensitivity. 14 out of 20 commercially available samples of F. ussuriensis were qualified, and 6 were unqualified, and the results of the two methods of identification were consistent. In this study, the combined detection method of LAMP and colloidal gold for nucleic acid was established to be specific, rapid, precise and visualized, which can provide a new technical idea for the detection of F. ussuriensis.


Asunto(s)
Fritillaria , Ácidos Nucleicos , Fritillaria/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Cartilla de ADN/genética , ADN , Sensibilidad y Especificidad
11.
Glycoconj J ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382616

RESUMEN

Lysosomal storage diseases (LSDs) are genetic disorders caused by mutations in lysosomal enzymes, lysosomal membrane proteins or genes related to intracellular transport that result in impaired lysosomal function. Currently, the primary treatment for several LSDs is enzyme replacement therapy (ERT), which involves intravenous administration of the deficient lysosomal enzymes to ameliorate symptoms. The efficacy of ERT largely depends on the mannose-6-phosphate (M6P) modification of the N-glycans associated with the enzyme, as M6P is a marker for the recognition and trafficking of lysosomal enzymes. In cells, N-glycan processing and M6P modification occur in the endoplasmic reticulum and Golgi apparatus. This is a complex process involving multiple enzymes. In the trans-Golgi network (TGN), M6P-modified enzymes are recognized by the cation-independent mannose-6-phosphate receptor (CIMPR) and transported to the lysosome to exert their activities. In this study, we used the 9th domain of CIMPR, which exhibits a high affinity for M6P binding, and fused it with the Fc domain of human immunoglobulin G1 (IgG1). The resulting fusion protein specifically binds to M6P-modified proteins. This provides a tool for the rapid detection and concentration of M6P-containing recombinant enzymes to assess the effectiveness of ERT. The advantages of this approach include its high specificity and sensitivity and may lead to the development of new treatments for LSDs.

12.
PLoS Biol ; 19(12): e3001474, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34879065

RESUMEN

Endoplasmic reticulum-associated degradation (ERAD) is a protein quality control pathway of fundamental importance to cellular homeostasis. Although multiple ERAD pathways exist for targeting topologically distinct substrates, all pathways require substrate ubiquitination. Here, we characterize a key role for the UBE2G2 Binding Region (G2BR) of the ERAD accessory protein ancient ubiquitous protein 1 (AUP1) in ERAD pathways. This 27-amino acid (aa) region of AUP1 binds with high specificity and low nanomolar affinity to the backside of the ERAD ubiquitin-conjugating enzyme (E2) UBE2G2. The structure of the AUP1 G2BR (G2BRAUP1) in complex with UBE2G2 reveals an interface that includes a network of salt bridges, hydrogen bonds, and hydrophobic interactions essential for AUP1 function in cells. The G2BRAUP1 shares significant structural conservation with the G2BR found in the E3 ubiquitin ligase gp78 and in vitro can similarly allosterically activate ubiquitination in conjunction with ERAD E3s. In cells, AUP1 is uniquely required to maintain normal levels of UBE2G2; this is due to G2BRAUP1 binding to the E2 and preventing its rapid degradation. In addition, the G2BRAUP1 is required for both ER membrane recruitment of UBE2G2 and for its activation at the ER membrane. Thus, by binding to the backside of a critical ERAD E2, G2BRAUP1 plays multiple critical roles in ERAD.


Asunto(s)
Degradación Asociada con el Retículo Endoplásmico/genética , Proteínas de la Membrana/fisiología , Enzimas Ubiquitina-Conjugadoras/fisiología , Secuencia de Aminoácidos/genética , Línea Celular Tumoral , Retículo Endoplásmico/metabolismo , Degradación Asociada con el Retículo Endoplásmico/fisiología , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/ultraestructura , Unión Proteica/genética , Dominios Proteicos/genética , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/ultraestructura , Ubiquitinación
14.
Clin Lab ; 70(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38345986

RESUMEN

BACKGROUND: von Willebrand disease (vWD), caused by mutations in the von Willebrand factor (vWF) coding gene, is a disease characterized by abnormal coagulation activity and a severe tendency for hemorrhage. Therefore, identifying mutations in vWF is important for diagnosing congenital vWD. METHODS: We studied a 23-year-old male vWD patient and his parents. Clotting methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB) levels, FVIII activity. Chromogenic substrate method was used to determine vWF antigen and activity. The platelet count was determined. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Clinical data, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, FX antigen levels, and the platelet count were collected. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulants. Mutations were screened by using whole-exome sequencing (WES) and were verified by using Sanger sequencing. RESULTS: The proband showed severely decreased vWF antigen, vWF activity, and FVIII activity. RIPA (RISTO-CETIN-induced platelet aggregation) was 0%. Data from WES showed that the proband carried compound heterozygous variants vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) and vWF: NM_000552.5 (c.6598+2T>C). The proband's mother carried variant vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) while the proband's father carried variant vWF: NM_000552.5 (c.6598+2T>C). All laboratory test indexes of the proband's parents, including vWF antigen, vWF activity, and FVIII activity, were within the normal ranges. CONCLUSIONS: We identified a compound heterozygosis with two novel mutations in vWF (c.3213C>A, c.6598+2T >C) in a family pedigree, and our results demonstrate that the compound heterozygous mutations probably exacerbate vWD.


Asunto(s)
Enfermedades de von Willebrand , Factor de von Willebrand , Masculino , Humanos , Adulto Joven , Adulto , Factor de von Willebrand/genética , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/genética , Linaje , Mutación , Fibrinógeno , China
15.
BMC Ophthalmol ; 24(1): 262, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898418

RESUMEN

BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease. METHODS: Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary. RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models. CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.


Asunto(s)
Síndromes de Ojo Seco , Microbioma Gastrointestinal , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/microbiología , Humanos , Microbioma Gastrointestinal/fisiología , Animales , Lágrimas/metabolismo
16.
BMC Pulm Med ; 24(1): 539, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39468531

RESUMEN

INTRODUCTION: Noninvasive ventilation (NIV) is widely used for sequential extubation in patients with chronic obstructive pulmonary disease (COPD). However, NIV may cause many adverse events such as claustrophobia, facial skin compression, air leakage, bloating, and even reflux aspiration, resulting in poor patient compliance/tolerance and high failure rate, especially for older adults who are at high risk of communication difficulties and consciousness disorder. High-flow nasal cannula (HFNC) oxygen therapy is a new alternative support to NIV, but whether it can effectively reduce the rate of re-intubation after extubation in elderly patients with COPD remains controversial. The purpose of this study is to explore the safety and efficacy of HFNC versus NIV for elderly COPD patients after extubation. METHODS AND ANALYSIS: This study is an investigator-initiated, single-center, prospective, non-inferior, randomized controlled trial. Elderly patients (age > 65 years) who have received invasive ventilation and was diagnosed with COPD will be randomly assigned to HFNC group or NIV group immediately after extubation with a planned enrollment of 168 patients. The primary outcomes will be reintubation rates at 72 h and 7 days after extubation. Secondary outcomes will include treatment failure, post-extubation vital signs and arterial blood gases, the scores of compliance and comfort of patients, duration of respiratory support after extubation, respiratory support related adverse events, sleep quality scores, usage of sedative and analgesic drugs after extubation, and the incidence of delirium. Additionally, clinical outcomes such as ventilator-free days at 28 days post-randomization, tracheotomy rate, duration of intensive care unit (ICU) and hospital stay, ICU and hospital mortality will be evaluated. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of West China Hospital of Sichuan University (2023-2284). Informed consent is required. It is expected that a follow-up randomized controlled trial will be conducted. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (ChiCTR2400087312).


Asunto(s)
Extubación Traqueal , Cánula , Ventilación no Invasiva , Terapia por Inhalación de Oxígeno , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Ventilación no Invasiva/métodos , Anciano , Terapia por Inhalación de Oxígeno/métodos , Extubación Traqueal/efectos adversos , Estudios Prospectivos , Masculino , Femenino , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Chem Biodivers ; : e202401726, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39301842

RESUMEN

The synchronous co-culture of Daldinia eschscholtzii and Colletotrichum pseudomajus produced one new linear polyketide, eschscholin C (1), along with three known compounds (2-4). One new acorane sesquiterpene, coldaldrin A (5), and one new amide derivative, coldaldamide A (6) as the probe for polyketide intermediate capture, and three known compounds (7-9) were isolated from the sequential co-culture of D. eschscholtzii with C. pseudomajus. The structures and absolute configurations of 1, 5 and 6 were established by spectroscopic analysis including 1D, 2D NMR, the calculations of the NMR, and ECD data. Most compounds showed significant antifungal activities against the tea pathogens C. pseudomajus, and Fusarium asiaticum with MICs of 2-8 µg/mL. Compound 4 also showed antifeedant activity against silkworms with feeding deterrence indices of 79 % at the concentration of 50 µg/cm2.

18.
J Sci Food Agric ; 104(5): 3100-3112, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38072653

RESUMEN

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. CONCLUSION: In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.


Asunto(s)
Curcumina , Nanopartículas , Curcumina/química , Antocianinas , Portadores de Fármacos/química , Polisacáridos , Nanopartículas/química , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Albúmina Sérica Bovina/química
19.
J Sci Food Agric ; 104(13): 7917-7927, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38829244

RESUMEN

BACKGROUND: Bacterial fruit blotch (BFB), known as the 'cancer' of cucurbits, is a seed-borne disease of melons caused by Acidovorax citrulli. Traditional chemical treatments for BFB are ineffective and adversely affect the environment. Using dielectric barrier discharge (DBD) nanosecond-pulsed plasma technology, melon seeds were treated to promote germination and growth and to control BFB. RESULTS: Based on the evaluation parameters of seed germination, seedling growth, leaf yellowing and bacterial infection after seed plasma treatments, 9 min at 20 kV was selected as the optimal plasma discharge parameter. In this study, seedling growth was significantly improved after treating melon seeds carrying A. citrulli using this discharge parameter. The number of first true leaves measured on the eighth day was 2.3 times higher and the disease index was reduced by 60.5% compared to the control group. Attenuated total reflectance-Fourier transform infrared measurements show that plasma treatments penetrate the seed coat and denature polysaccharides and proteins in the seed kernel, affecting their growth and sterilization properties. CONCLUSION: Pre-sowing treatment of melon seeds carrying A. citrulli using nanosecond-pulsed plasma technology can effectively control seedling BFB disease and promote melon seedling growth by optimizing DBD parameters. © 2024 Society of Chemical Industry.


Asunto(s)
Comamonadaceae , Cucurbitaceae , Frutas , Germinación , Enfermedades de las Plantas , Gases em Plasma , Plantones , Semillas , Plantones/crecimiento & desarrollo , Plantones/microbiología , Cucurbitaceae/crecimiento & desarrollo , Cucurbitaceae/microbiología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , Comamonadaceae/crecimiento & desarrollo , Gases em Plasma/farmacología , Frutas/microbiología , Frutas/crecimiento & desarrollo , Frutas/química , Semillas/crecimiento & desarrollo , Semillas/microbiología , Semillas/química
20.
Int Wound J ; 21(3): e14675, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38484699

RESUMEN

A meta-analysis was conducted to evaluate the effects of loose combined cutting seton surgery on wound healing and pain in patients with high anal fistula, aiming to provide evidence-based medical evidence for surgical method selection for these patients. A comprehensive computerized search of PubMed, Cochrane Library, EMBASE, Wanfang and China National Knowledge Infrastructure databases was conducted to collect all relevant studies published up to November 2023, evaluating the effects of loose combined cutting seton surgery in treating patients with high anal fistulas. Two researchers independently screened, extracted data, and assessed the quality of the identified studies. RevMan 5.4 software was employed for data analysis. Overall, 16 articles were included, comprising 1124 patients, with 567 undergoing loose combined cutting seton surgery and 557 undergoing simple cutting seton surgery. The analysis revealed patients undergoing loose combined cutting seton surgery had a higher rate of postoperative wound healing (97.44% vs. 81.69%, odds ratio [OR]: 7.49, 95% confidence interval [CI]: 4.29-13.10, p < 0.00001), shorter wound healing time (standardized mean differences [SMD]: -1.48, 95% CI: -1.89 to -1.08, p < 0.00001), lower postoperative wound pain scores (SMD: -2.51, 95% CI: -3.51 to -1.51, p < 0.00001), and a lower rate of postoperative complications (3.43% vs. 20.83%, OR: 0.13, 95% CI: 0.05-0.31, p < 0.00001). The current evidence suggests that compared to simple cutting seton surgery, loose combined cutting seton surgery in treating high anal fistulas can promote postoperative wound healing, shorten wound healing time, alleviate pain, and reduce the incidence of postoperative complications, making it a worthy clinical practice for widespread application.


Asunto(s)
Dolor Postoperatorio , Fístula Rectal , Cicatrización de Heridas , Humanos , Fístula Rectal/cirugía , Femenino , Masculino , Adulto , Persona de Mediana Edad , Anciano , Resultado del Tratamiento
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