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1.
Commun Biol ; 7(1): 1068, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39215048

RESUMEN

Sugar content is a critical indicator of fruit quality and is mainly controlled by sugar transporters. Sugars will eventually be exported transporters (SWEET) proteins play an indispensable role in sugar allocation between and within plant organs. Sucrose is the major sugar in many fruits and the predominant form of sugar translocated in peach (Prunus persica). However, the role of the multiple peach SWEET genes in sucrose allocation to fruit remains elusive. In this study, a total of 19 SWEET candidates have been identified in the peach genome, and two Clade III SWEET genes, PpSWEET9a and PpSWEET14, are found to be highly expressed in mature source leaves and branches. Complementation assays, transgene manipulations, and protein interaction studies reveal that PpSWEET9a and PpSWEET14 serve as sucrose efflux proteins and form a heterooligomer that synergistically directs sucrose allocation from source leaves to fruits. Our findings provide insights into the effect of SWEETs on sugar accumulation in peach fruit and identify genetic candidates for improving fruit quality.


Asunto(s)
Frutas , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta , Proteínas de Plantas , Prunus persica , Sacarosa , Prunus persica/genética , Prunus persica/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Sacarosa/metabolismo , Frutas/metabolismo , Frutas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genética
2.
Anal Methods ; 16(36): 6134-6155, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39207184

RESUMEN

Considerable progress has been made in the electrochemical determination of acetaminophen (AP) over the past few decades. Nanomaterials or enzymes as electrode modifiers greatly improve the performance of AP electrochemical sensors. This review focuses on the development potential, detection principles and techniques for the electrochemical analysis of AP. In particular, the design and construction of AP electrochemical sensors are discussed from the perspective of non-enzyme materials (such as nanomaterials, including precious metals, transition metals and non-metals) and enzyme substances (such as aryl acylamidase, polyphenol oxidase and horseradish peroxidase). Moreover, the influencing factors for AP electrochemical sensors and the simultaneous detection of AP and other targets are summarized, and the future prospective of AP electrochemical sensors is outlined. This review provides a reference and guidance for the development and application of electrochemical sensors for AP detection.


Asunto(s)
Acetaminofén , Técnicas Electroquímicas , Acetaminofén/análisis , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Humanos , Técnicas Biosensibles/métodos , Electrodos , Analgésicos no Narcóticos/análisis , Nanoestructuras/química
3.
Curr Med Sci ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145837

RESUMEN

OBJECTIVE: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. METHODS: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. CONCLUSION: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.

5.
Diagnostics (Basel) ; 14(16)2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39202240

RESUMEN

Given the diversity of medical images, traditional image segmentation models face the issue of domain shift. Unsupervised domain adaptation (UDA) methods have emerged as a pivotal strategy for cross modality analysis. These methods typically utilize generative adversarial networks (GANs) for both image-level and feature-level domain adaptation through the transformation and reconstruction of images, assuming the features between domains are well-aligned. However, this assumption falters with significant gaps between different medical image modalities, such as MRI and CT. These gaps hinder the effective training of segmentation networks with cross-modality images and can lead to misleading training guidance and instability. To address these challenges, this paper introduces a novel approach comprising a cross-modality feature alignment sub-network and a cross pseudo supervised dual-stream segmentation sub-network. These components work together to bridge domain discrepancies more effectively and ensure a stable training environment. The feature alignment sub-network is designed for the bidirectional alignment of features between the source and target domains, incorporating a self-attention module to aid in learning structurally consistent and relevant information. The segmentation sub-network leverages an enhanced cross-pseudo-supervised loss to harmonize the output of the two segmentation networks, assessing pseudo-distances between domains to improve the pseudo-label quality and thus enhancing the overall learning efficiency of the framework. This method's success is demonstrated by notable advancements in segmentation precision across target domains for abdomen and brain tasks.

6.
Redox Biol ; 75: 103297, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39127015

RESUMEN

Cardiovascular disease (CVD) is one of the leading causes of mortality in humans, and oxidative stress plays a pivotal role in disease progression. This phenomenon typically arises from weakening of the cellular antioxidant system or excessive accumulation of peroxides. This review focuses on a specialized form of oxidative stress-disulfide stress-which is triggered by an imbalance in the glutaredoxin and thioredoxin antioxidant systems within the cell, leading to the accumulation of disulfide bonds. The genesis of disulfide stress is usually induced by extrinsic pathological factors that disrupt the thiol-dependent antioxidant system, manifesting as sustained glutathionylation of proteins, formation of abnormal intermolecular disulfide bonds between cysteine-rich proteins, or irreversible oxidation of thiol groups to sulfenic and sulfonic acids. Disulfide stress not only precipitates the collapse of the antioxidant system and the accumulation of reactive oxygen species, exacerbating oxidative stress, but may also initiate cellular inflammation, autophagy, and apoptosis through a cascade of signaling pathways. Furthermore, this review explores the detrimental effects of disulfide stress on the progression of various CVDs including atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, diabetic cardiomyopathy, cardiac hypertrophy, and heart failure. This review also proposes several potential therapeutic avenues to improve the future treatment of CVDs.


Asunto(s)
Enfermedades Cardiovasculares , Disulfuros , Estrés Oxidativo , Humanos , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Disulfuros/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Antioxidantes/metabolismo , Oxidación-Reducción , Tiorredoxinas/metabolismo
7.
Medicine (Baltimore) ; 103(23): e38424, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847721

RESUMEN

RATIONAL: Congenital hepatic fibrosis (CHF) is a rare autosomal recessive genetic disease, which is often diagnosed in children and young adults. The clinical manifestations of CHF were lack of specificity, mainly including portal hypertension related symptoms and signs, and normal or mildly abnormal liver function. When no obvious varices are indicated under endoscope, it can easily lead to misdiagnosis or missed diagnosis. We report this case in the hope of raising awareness of this disease. PATIENT CONCERNS: A 31 years old male patient with major clinical manifestations of unexplained thrombocytopenia for 5 years. DIAGNOSES: Results of ultrasound, magnetic resonance imaging (MRI) and computed tomography portal venography (CTV) showed that patient had liver cirrhosis with portal hypertension and liver biopsy revealed CHF. INTERVENTION: Patient received ursodeoxycholic acid tablets, fuzheng huayu capsule, ganshuang granule, etc for liver protection treatment. OUTCOMES: The condition of patient stabilized after symptomatic treatment. Spleen resection will be considered during follow-up. LESSONS: This case reminds us that in case of patients with negative endoscopic evaluation, ultrasonic, computed tomography (CT) and MRI examination should be performed at the same time to determine whether patients have portal hypertension. When patients with normal or mildly abnormal liver function had unexplained liver cirrhosis complicated with portal hypertension, the possibility of CHF should be considered.


Asunto(s)
Várices Esofágicas y Gástricas , Cirrosis Hepática , Humanos , Masculino , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/diagnóstico , Adulto , Cirrosis Hepática/complicaciones , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Enfermedades Genéticas Congénitas/complicaciones , Enfermedades Genéticas Congénitas/diagnóstico , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos
9.
EBioMedicine ; 104: 105181, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38838469

RESUMEN

BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).


Asunto(s)
COVID-19 , Quirópteros , SARS-CoV-2 , Animales , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Humanos , COVID-19/virología , Quirópteros/virología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Organoides/virología , Organoides/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/virología , Cricetinae , Furina/metabolismo , Células Epiteliales/virología , Células Vero , Chlorocebus aethiops
10.
Small ; 20(37): e2403198, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38738744

RESUMEN

Hydrogen bonding as a multifunctional tool has always influenced the structure of hybrid perovskites. Compared with the research on hydrogen bonding, the study of halogen-halogen interactions on the structure and properties of hybrid perovskites is still in its early stages. Herein, a polar bilayered hybrid perovskite (IEA)2FAPb2I7 (IEA+ is 2-iodoethyl-1-ammonium, FA is formamidinium) with iodine-substituted spacer is successfully constructed by changing the configuration of interlayer cations and regulating non-covalent interactions at the organic-inorganic interface, which shows a shorter interlayer spacing and higher density (ρ = 3.862 g cm-3). The generation of structure polarity in (IEA)2FAPb2I7 is caused by the synergistic effect of hydrogen bonding and halogen-halogen interactions. Especially, as the length of the carbon chain in organic cations decreases, the I---I interaction in the system gradually strengthens, which may be the main reason for the symmetry-breaking. Polarity-induced bulk photovoltaics (Voc = 1.0 V) and higher density endow the device based on (I-EA)2FAPb2I7 exhibit a high sensitivity of 175.6 µC Gy-1 cm-2 and an ultralow detection limit of 60.4 nGy s-1 at 0 V bias under X-ray irradiation. The results present a facile approach for designing polar multifunctional hybrid perovskites, also providing useful assistance for future research on halogen-halogen interactions.

11.
Int Microbiol ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805155

RESUMEN

Soluble phosphorus scarcity severely limits plant growth and crop yield. In this study, a strain of inorganic phosphorus-solubilizing bacteria, Lysinibacillus sphaericus, was isolated from rice rhizosphere soil. The available phosphorus content in liquid inorganic phosphorus identification medium and in L. sphaericus-inoculated soil increased from 204.28 mg/L to 1124.68 mg/L and from 4.75 mg/kg to 7.04 mg/kg, respectively. The pH decreased significantly from 6.87 to 6.14. Incubation with L. sphaericus significantly increased malic and succinic acid content in the liquid inorganic phosphorus identification medium and increased acid phosphatase and alkaline phosphatase activity in the soil. Inoculation with L. sphaericus significantly increased rice growth, chlorophyll a/b content, and photosynthesis by increasing the soluble phosphorus content in the rice rhizosphere soil under phosphorus-deficient conditions. Further analysis revealed that L. sphaericus improved soil phosphorus release by decreasing soil pH and promoting acid phosphatase and alkaline phosphatase activity. This study supports the production of microbial fertilizers to improve rice yield in phosphorus-deficient conditions.

12.
Ther Adv Hematol ; 15: 20406207241245190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737005

RESUMEN

Background: Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with ß-thalassemia major (ß-TM) after hematopoietic stem cell transplantation (HSCT). Objectives: A model to predict the risk of SFPR in ß-TM patients after HSCT was developed. Design: A retrospective study was used to develop the prediction model. Methods: The clinical data for 218 ß-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model. Results: The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%. Conclusion: We constructed a nomogram model to predict the risk of SFPR in patients with ß-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

13.
Front Psychol ; 15: 1379705, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784620

RESUMEN

Background: The exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters. Aim: The study aims to identify distinct personality profiles among university students based on Eysenck's personality dimensions and investigate how these profiles differ across psychological constructs. Method: A quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles. Results: Four distinct personality profiles emerged: 'The Reserved Analyst,' 'The Social Diplomat,' 'The Unconventional Pragmatist,' and 'The Impulsive Truth-Teller.' Significant differences were found among these profiles on various psychological constructs. 'The Social Diplomat' exhibited the most adaptive psychological profile, with higher cognitive reappraisal (F = 45.818, p < 0.001, η2 = 0.163), meaning in life (F = 17.764, p < 0.001, η2 = 0.070), and positive coping (F = 40.765, p < 0.001, η2 = 0.148) compared to other profiles. Conversely, 'The Reserved Analyst' showed higher intolerance of uncertainty (F = 13.854, p < 0.001, η2 = 0.056) and state anxiety (F = 26.279, p < 0.001, η2 = 0.101). Conclusion: This study enriches the understanding of personality traits in relation to psychological constructs within the context of university student populations. By identifying distinct personality profiles, it lays the groundwork for developing tailored mental health strategies that cater to the specific needs of different student groups.

14.
Rheumatol Ther ; 11(3): 755-771, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38662148

RESUMEN

INTRODUCTION: Transforming growth factor beta (TGFß) cytokines (TGFß1, TGFß2, and TGFß3) play critical roles in tissue fibrosis. However, treatment with systemic pan-TGFß inhibitors have demonstrated unacceptable toxicities. In this study, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7303509, a high-affinity, TGFß3-specific, humanized immunoglobulin G1 monoclonal antibody, in healthy adult volunteers (HVs). METHODS: This phase 1a, randomized, double-blind trial included six cohorts for evaluation, with each cohort receiving single doses of placebo or RO7303509, administered intravenously (IV; 50 mg, 150 mg, 240 mg) or subcutaneously (SC; 240 mg, 675 mg, 1200 mg). The frequency and severity of adverse events (AEs) and RO7303509 serum concentrations were monitored throughout the study. We also measured serum periostin and cartilage oligomeric matrix protein (COMP) by immunoassay and developed a population pharmacokinetics model to characterize RO7303509 serum concentrations. RESULTS: The study enrolled 49 HVs, with a median age of 39 (range 18-73) years. Ten (27.8%) RO7303509-treated subjects reported 24 AEs, and six (30.8%) placebo-treated subjects reported six AEs. The most frequent AEs related to the study drug were injection site reactions and infusion-related reactions. Maximum serum concentrations (Cmax) and area under the concentration-time curve from time 0 to infinity (AUC0-inf) values for RO7303509 appeared to increase dose-proportionally across all doses tested. Serum concentrations across cohorts were best characterized by a two-compartment model plus a depot compartment with first-order SC absorption kinetics. No subjects tested positive for anti-drug antibodies (ADAs) at baseline; one subject (2.8%; 50 mg IV) tested positive for ADAs at a single time point (day 15). No clear pharmacodynamic effects were observed for periostin or COMP upon TGFß3 inhibition. CONCLUSION: RO7303509 was well tolerated at single SC doses up to 1200 mg in HVs with favorable pharmacokinetic data that appeared to increase dose-proportionally. TGFß3-specific inhibition may be suitable for development as a chronic antifibrotic therapy. TRIAL REGISTRATION: ISRCTN13175485.

15.
Clin Pharmacol Drug Dev ; 13(6): 655-664, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38651245

RESUMEN

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.


Asunto(s)
Estudios Cruzados , Voluntarios Sanos , Componente Amiloide P Sérico , Equivalencia Terapéutica , Humanos , Masculino , Método Doble Ciego , Adulto , Componente Amiloide P Sérico/metabolismo , Femenino , Persona de Mediana Edad , Adulto Joven , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Área Bajo la Curva , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Administración Intravenosa
16.
Infect Genet Evol ; 121: 105594, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38636619

RESUMEN

The prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified that CCR3 exhibited significant natural selection signals in sub-Sahara Africans. Within the CCR3 gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory of CCR3 rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increased CCR3 expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased blood CCR3 expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are resistant to critically ill COVID-19 due to natural selection and identify CCR3 as a potential novel therapeutic target.


Asunto(s)
COVID-19 , Enfermedad Crítica , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores CCR3 , SARS-CoV-2 , Selección Genética , Humanos , África del Sur del Sahara/epidemiología , Población Negra/genética , COVID-19/genética , COVID-19/virología , COVID-19/epidemiología , Frecuencia de los Genes , Haplotipos , Análisis de la Aleatorización Mendeliana , Receptores CCR3/genética , SARS-CoV-2/genética , Pueblo Africano Subsahariano
17.
Int J Biol Sci ; 20(6): 2219-2235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617542

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Metabolismo de los Lípidos/genética , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Receptores de Quimiocina , Inflamación
18.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38610517

RESUMEN

In the precise point positioning/real-time kinematic (PPP-RTK) technique, high-precision ionospheric delay correction information is an important prerequisite for rapid PPP convergence. The commonly used ionospheric modeling approaches in the PPP-RTKs only take the trend term of the ionospheric total electron content (TEC) variations into account. As a result, the residual ionospheric delay still affects the positioning solutions. In this study, we propose a two-step regional ionospheric modeling approach that involves combining a polynomial fitting model (PFM) and a Kriging interpolation (KI) model. In the first step, a polynomial fitting method is used to model the trend term of the ionospheric TEC variations. In the second step, a KI method is used to compensate for the residual term of the ionospheric TEC variations. Datasets collected from continuously operating reference stations (CORSs) in Hunan Province, China, are used to validate the PFM/KI method by comparing with a single PFM method and a combined PFM and inverse distance weighting interpolation (IDWI) method. The experimental results show that the two-step PFM/KI modeled ionospheric delay achieves an average root mean square (RMS) error of 1.8 cm, which is improved by about 48% and 23% when compared with the PFM and PFM/IDWI methods, respectively. Regarding the positioning performance, the PPP-RTK with the PFM/KI method takes an average of 1.8 min or 4.0 min to converge to a positioning accuracy of 1.3 cm or 2.5 cm in the horizontal and vertical directions, respectively. The convergence times are decreased by about 18% and 14% in the horizontal direction and 9% and 5% in the vertical direction over the PFM and the PFM/IDWI methods, respectively.

19.
Angew Chem Int Ed Engl ; 63(17): e202318800, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38443316

RESUMEN

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).


Asunto(s)
Nanopartículas , Ácidos Nucleicos , Colorantes Fluorescentes/química , Nanopartículas/química , Técnicas de Amplificación de Ácido Nucleico
20.
Phys Chem Chem Phys ; 26(12): 9096-9111, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38456310

RESUMEN

As one of the most promising energy storage devices, supercapacitors exhibit a higher power density than batteries. However, its low energy density usually requires high-performance electrode materials. Although the RuO2 material shows desirable properties, its high cost and toxicity significantly limit its application in supercapacitors. Recent developments demonstrated that Co-based materials have emerged as a promising alternative to RuO2 for supercapacitors due to their low cost, favorable redox reversibility and environmental friendliness. In this paper, the morphological control and performance engineering of Co-based materials are systematically reviewed. Firstly, the principle of supercapacitors is briefly introduced, and the characteristics and advantages of pseudocapacitors are emphasized. The special forms of cobalt-based materials are introduced, including 1D, 2D and 3D nanomaterials. After that, the ways to enhance the properties of cobalt-based materials are discussed, including adding conductive materials, constructing heterostructures and doping heteroatoms. Particularly, the influence of morphological control and modification methods on the electrochemical performances of materials is highlighted. Finally, the application prospect and development direction of Co-based materials are proposed.

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