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1.
Cell ; 186(15): 3245-3260.e23, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37369203

RESUMEN

Terrestrial organisms developed circadian rhythms for adaptation to Earth's quasi-24-h rotation. Achieving precise rhythms requires diurnal oscillation of fundamental biological processes, such as rhythmic shifts in the cellular translational landscape; however, regulatory mechanisms underlying rhythmic translation remain elusive. Here, we identified mammalian ATXN2 and ATXN2L as cooperating master regulators of rhythmic translation, through oscillating phase separation in the suprachiasmatic nucleus along circadian cycles. The spatiotemporal oscillating condensates facilitate sequential initiation of multiple cycling processes, from mRNA processing to protein translation, for selective genes including core clock genes. Depleting ATXN2 or 2L induces opposite alterations to the circadian period, whereas the absence of both disrupts translational activation cycles and weakens circadian rhythmicity in mice. Such cellular defect can be rescued by wild type, but not phase-separation-defective ATXN2. Together, we revealed that oscillating translation is regulated by spatiotemporal condensation of two master regulators to achieve precise circadian rhythm in mammals.


Asunto(s)
Relojes Circadianos , Ratones , Animales , Relojes Circadianos/genética , Ritmo Circadiano/fisiología , Núcleo Supraquiasmático/metabolismo , Procesamiento Proteico-Postraduccional , Mamíferos
2.
Cell ; 153(5): 963-75, 2013 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-23706735

RESUMEN

The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendodermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a "seesaw model" in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.


Asunto(s)
Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Factores de Transcripción/metabolismo , Animales , Células Madre Embrionarias/metabolismo , Fibroblastos/metabolismo , Factor de Transcripción GATA3/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Ratones , Modelos Biológicos , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Estómago/citología
3.
PLoS Comput Biol ; 20(6): e1011882, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38838038

RESUMEN

In embryonic development and organogenesis, cells sharing identical genetic codes acquire diverse gene expression states in a highly reproducible spatial distribution, crucial for multicellular formation and quantifiable through positional information. To understand the spontaneous growth of complexity, we constructed a one-dimensional division-decision model, simulating the growth of cells with identical genetic networks from a single cell. Our findings highlight the pivotal role of cell division in providing positional cues, escorting the system toward states rich in information. Moreover, we pinpointed lateral inhibition as a critical mechanism translating spatial contacts into gene expression. Our model demonstrates that the spatial arrangement resulting from cell division, combined with cell lineages, imparts positional information, specifying multiple cell states with increased complexity-illustrated through examples in C.elegans. This study constitutes a foundational step in comprehending developmental intricacies, paving the way for future quantitative formulations to construct synthetic multicellular patterns.


Asunto(s)
Redes Reguladoras de Genes , Modelos Biológicos , Animales , Redes Reguladoras de Genes/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/embriología , Caenorhabditis elegans/crecimiento & desarrollo , División Celular/fisiología , División Celular/genética , Biología Computacional , Desarrollo Embrionario/fisiología , Desarrollo Embrionario/genética , Linaje de la Célula , Simulación por Computador , Regulación del Desarrollo de la Expresión Génica/genética
5.
Proc Natl Acad Sci U S A ; 119(31): e2120309119, 2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-35881797

RESUMEN

The Intertropical Convergence Zone (ITCZ) is a salient feature of tropical atmospheric circulation characterized by intense convective clouds and rainfall north of the equator. Climate models, however, commonly experience the double-ITCZ problem-the tendency to produce another strong precipitation band but south of the equator. Here, we describe coupled interaction between the ITCZ and the North Equatorial Countercurrent (NECC) that is relevant to this problem. This current is a major component of the tropical Pacific upper-ocean circulation, which flows against easterly trade winds and transports warm water from the western Pacific eastward. Its core follows the latitudinal position of the ITCZ. Trade winds converge toward the ITCZ, creating a local minimum in zonal winds and generating positive wind stress curl that maintains an eastward current despite westward winds. We show that interaction between the ITCZ and the NECC involves positive feedback: a stronger NECC advects warm water from the western Pacific to the colder east thus increasing sea surface temperature (SST) along its path, intensifying convection within the ITCZ and hence strengthening wind stress curl, further strengthening the NECC. To demonstrate this wind stress curl-advection-SST-precipitation (WASP) feedback, we conduct climate model experiments in which we progressively strengthen the surface Ekman component of the NECC and observe the intensification of the ITCZ and the entire NECC. Consequently, a weak NECC leads to a weak ITCZ, which can contribute to the double-ITCZ problem in climate models, since weak wind convergence north of the equator enables stronger convergence in the south.

6.
Neuroimage ; 291: 120579, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38537766

RESUMEN

Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of ∼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72∼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.


Asunto(s)
Conectoma , Recien Nacido Prematuro , Lactante , Recién Nacido , Humanos , Preescolar , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Recién Nacido de muy Bajo Peso
7.
BMC Plant Biol ; 24(1): 230, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561687

RESUMEN

BACKGROUND: Dendrobium spp. comprise a group of tropical orchids with ornamental and medicinal value. Dendrobium spp. are sensitive to low temperature, and the underlying cold response regulatory mechanisms in this group are unclear. To understand how these plants respond to cold stress, we compared the transcriptomic responses of the cold-tolerant cultivar 'Hongxing' (HX) and the cold-sensitive cultivar 'Sonia Hiasakul' (SH) to cold stress. RESULTS: Chemometric results showed that the physiological response of SH in the later stages of cold stress is similar to that of HX throughout the cold treatment. Orthogonal partial least squares discriminant analysis (OPLS-DA) revealed that soluble protein content and peroxidase activity are key physiological parameters for assessing the cold tolerance of these two Dendrobium spp. cultivars. Additionally, weighted gene co-expression network analysis (WGCNA) results showed that many cold response genes and metabolic pathways significantly associated with the physiological indices were enriched in the 12 detected modules. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses of the 105 hub genes showed that Dendrobium spp. adapt to cold stress by regulating signal transduction, phytohormones, transcription factors, protein translation and modification, functional proteins, biosynthesis and metabolism, cell structure, light, and the circadian clock. Hub genes of the cold stress response network included the remorin gene pp34, the abscisic acid signaling pathway-related genes PROTEIN PHOSPATASE 2 C (PP2C), SNF1-RELATED PROTEIN KINASE 2 (SnRK2), ABRE-BINDING FACTOR 1 (ABF1) and SKI-INTERACTING PROTEIN 17 (SKIP17), the Ca2+ signaling-related GTP diphosphokinase gene CRSH1, the carbohydrate-related gene STARCH SYNTHASE 2 (SS2), the cell wall biosynthesis gene CINNAMYL ALCOHOL DEHYDROGENASE (CAD7), and the endocytosis-related gene VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 52 A (VPS52A). CONCLUSIONS: The cold-responsive genes and metabolic pathways of Dendrobium spp. revealed in this study provide important insight to enable the genetic enhancement of cold tolerance in Dendrobium spp., and to facilitate cold tolerance breeding in related plants.


Asunto(s)
Respuesta al Choque por Frío , Dendrobium , Respuesta al Choque por Frío/genética , Dendrobium/genética , Fitomejoramiento , Perfilación de la Expresión Génica , Transcriptoma , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas
8.
BMC Plant Biol ; 24(1): 541, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872084

RESUMEN

BACKGROUND: The glandular trichomes of tobacco (Nicotiana tabacum) can efficiently produce secondary metabolites. They act as natural bioreactors, and their natural products function to protect plants against insect-pests and pathogens and are also components of industrial chemicals. To clarify the molecular mechanisms of tobacco glandular trichome development and secondary metabolic regulation, glandular trichomes and glandless trichomes, as well as other different developmental tissues, were used for RNA sequencing and analysis. RESULTS: By comparing glandless and glandular trichomes with other tissues, we obtained differentially expressed genes. They were obviously enriched in KEGG pathways, such as cutin, suberine, and wax biosynthesis, flavonoid and isoflavonoid biosynthesis, terpenoid biosynthesis, and plant-pathogen interaction. In particular, the expression levels of genes related to the terpenoid, flavonoid, and wax biosynthesis pathway mainly showed down-regulation in glandless trichomes, implying that they lack the capability to synthesize certain exudate compounds. Among the differentially expressed genes, 234 transcription factors were found, including AP2-ERFs, MYBs, bHLHs, WRKYs, Homeoboxes (HD-ZIP), and C2H2-ZFs. These transcription factor and genes that highly expressed in trichomes or specially expressed in GT or GLT. Following the overexpression of R2R3-MYB transcription factor Nitab4.5_0011760g0030.1 in tobacco, an increase in the number of branched glandular trichomes was observed. CONCLUSIONS: Our data provide comprehensive gene expression information at the transcriptional level and an understanding of the regulatory pathways involved in glandular trichome development and secondary metabolism.


Asunto(s)
Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Nicotiana , Tricomas , Tricomas/genética , Tricomas/metabolismo , Tricomas/crecimiento & desarrollo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/crecimiento & desarrollo , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
9.
J Virol ; 97(9): e0050523, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37676003

RESUMEN

SARS-CoV-2 has been expanding its host range, among which the white-tailed deer (WTD), Odocoileus virginianus, became the first wildlife species infected on a large scale and might serve as a host reservoir for variants of concern (VOCs) in case no longer circulating in humans. In this study, we comprehensively assessed the binding of the WTD angiotensin-converting enzyme 2 (ACE2) receptor to the spike (S) receptor-binding domains (RBDs) from the SARS-CoV-2 prototype (PT) strain and multiple variants. We found that WTD ACE2 could be broadly recognized by all of the tested RBDs. We further determined the complex structures of WTD ACE2 with PT, Omicron BA.1, and BA.4/5 S trimer. Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding. This study deepens our understanding of the interspecies transmission mechanisms of SARS-CoV-2 and further addresses the importance of constant monitoring on SARS-CoV-2 infections in wild animals. IMPORTANCE Even if we manage to eliminate the virus among humans, it will still circulate among wildlife and continuously be transmitted back to humans. A recent study indicated that WTD may serve as reservoir for nearly extinct SARS-CoV-2 strains. Therefore, it is critical to evaluate the binding abilities of SARS-CoV-2 variants to the WTD ACE2 receptor and elucidate the molecular mechanisms of binding of the RBDs to assess the risk of spillback events.

10.
Cell Immunol ; 399-400: 104827, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38733699

RESUMEN

The need to contrive interventions to curb the rise in cancer incidence and mortality is critical for improving patients' prognoses. Adoptive cell therapy is challenged with quality large-scale production, heightening its production cost. Several cancer types have been associated with the expression of highly-immunogenic CTAG1 and CTAG2 antigens, which share common epitopes. Targeting two antigens on the same cancer could improve the antitumor response of TCR-T cells. In this study, we exploited an efficient way to generate large-fold quality TCR-T cells and also demonstrated that the common epitopes of CTAG1 and CTAG2 antigens provide an avenue for improved cancer-killing via dual-antigen-epitope targeting. Our study revealed that xeno/sera-free medium could expand TCR-T cells to over 500-fold, posing as a better replacement for FBS-supplemented media. Human AB serum was also shown to be a good alternative in the absence of xeno/sera-free media. Furthermore, TCR-T cells stimulated with beads-coated T-activator showed a better effector function than soluble T-activator stimulated TCR-T cells. Additionally, TCR-T cells that target multiple antigens in the same cancer yield better anticancer activity than those targeting a single antigen. This showed that targeting multiple antigens with a common epitope may enhance the antitumor response efficacy of T cell therapies.


Asunto(s)
Antígenos de Neoplasias , Inmunoterapia Adoptiva , Receptores de Antígenos de Linfocitos T , Antígenos de Neoplasias/inmunología , Humanos , Inmunoterapia Adoptiva/métodos , Receptores de Antígenos de Linfocitos T/inmunología , Animales , Epítopos de Linfocito T/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Ratones , Línea Celular Tumoral , Linfocitos T/inmunología , Epítopos/inmunología
11.
Opt Express ; 32(9): 16362-16370, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859265

RESUMEN

Particle manipulation through the transfer of light or sound momentum has emerged as a powerful technique with immense potential in various fields, including cell biology, microparticle assembly, and lab-on-chip technology. Here, we present a novel method called Programmable Photoacoustic Manipulation (PPAM) of microparticles in liquid, which enables rapid and precise arrangement and controllable transport of numerous silica particles in water. Our approach leverages the modulation of pulsed laser using digital micromirror devices (DMD) to generate localized Lamb waves in a stainless steel membrane and acoustic waves in water. The particles undergo a mechanical force of about several µN due to membrane vibrations and an acoustic radiation force of about tens of nN from the surrounding water. Consequently, this approach surpasses the efficiency of optical tweezers by effectively countering the viscous drag imposed by water and can be used to move thousands of particles on the membrane. The high power of the pulsed laser and the programmability of the DMD enhance the flexibility in particle manipulation. By integrating the benefits of optical and acoustic manipulation, this technique holds great promise for advancing large-scale manipulation, cell assembly, and drug delivery.

12.
Cancer Cell Int ; 24(1): 64, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336680

RESUMEN

BACKGROUND: Esophageal cancer (EC) is a global canker notorious for causing high mortality due to its relentless incidence rate, convoluted with unyielding recurrence and metastasis. However, these intricacies of EC are associated with an immoderate expression of NY-ESO-1 antigen, presenting a lifeline for adoptive T cell therapy. We hypothesized that naturally isolated higher-affinity T cell receptors (TCRs) that bind to NY-ESO-1 would allow T lymphocytes to target EC with a pronounced antitumor response efficacy. Also, targeting TRPV2, which is associated with tumorigenesis in EC, creates an avenue for dual-targeted therapy. We exploited the dual-targeting antitumor efficacy against EC. METHODS: We isolated antigen-specific TCRs (asTCRs) from a naive library constructed with TCRs obtained from enriched cytotoxic T lymphocytes. The robustness of our asTCRs and their TCR-T cell derivatives, Tranilast (TRPV2 inhibitor), and their bivalent treatment were evaluated with prospective cross-reactive human-peptide variants and tumor cells. RESULTS: Our study demonstrated that our naive unenhanced asTCRs and their TCR-Ts perpetuated their cognate HLA-A*02:01/NY-ESO-1(157-165) specificity, killing varying EC cells with higher cytotoxicity compared to the known affinity-enhanced TCR (TCRe) and its wild-type (TCR0) which targets the same NY-ESO-1 antigen. Furthermore, the TCR-Ts and Tranilast bivalent treatment showed superior EC killing compared to any of their monovalent treatments of either TCR-T or Tranilast. CONCLUSION: Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.

13.
Biopolymers ; : e23605, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864249

RESUMEN

Chemotherapy plays a crucial role in the clinical treatment of triple-negative breast cancer (TNBC), but drug resistance limits its clinical application. The active ingredients of Chaihu Shugan Powder (CSP; Bupleurum Liver-Coursing Powder), quercetin and luteolin, both belong to flavonoid compounds and have significant anti-tumor potential, which can promote chemotherapy sensitivity. However, the correlation between the two and TNBC paclitaxel (PTX) chemotherapy sensitivity is unknown. We collected herbal components of CSP from the TCMSP database, and screened effective molecules and corresponding targets. STRING database was utilized to construct a protein-protein interaction network combining effective molecules and target genes. The top 50 nodes ranked by affinity were chosen for subsequent functional analysis, and the drug-active ingredient-gene interaction network was established using Cytoscape software. Molecular docking was used to determine the small molecules that target TNBC PTX resistance. The "clusterProfiler" package was utilized for GO and KEGG enrichment analyses on the top 50 genes to determine the pathways affected by CSP. Cell counting and colony formation assays evaluated cell viability, IC50 values, and proliferation capacity. Flow cytometry tested PTX intracellular accumulation. Western blot assayed the expression of TNF pathway-related proteins. Active ingredients of CSP, quercetin and luteolin, could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization. Quercetin and luteolin repressed the TNF signaling pathway and promoted PTX chemotherapy sensitization. Quercetin and luteolin could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization through the TNF signaling pathway. Therefore, the use of quercetin and luteolin plus PTX treatment provides a prospective strategy for TNBC treatment.

14.
PLoS Comput Biol ; 19(5): e1011100, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37186644

RESUMEN

Non-ribosomal peptide synthetase (NRPS) is a diverse family of biosynthetic enzymes for the assembly of bioactive peptides. Despite advances in microbial sequencing, the lack of a consistent standard for annotating NRPS domains and modules has made data-driven discoveries challenging. To address this, we introduced a standardized architecture for NRPS, by using known conserved motifs to partition typical domains. This motif-and-intermotif standardization allowed for systematic evaluations of sequence properties from a large number of NRPS pathways, resulting in the most comprehensive cross-kingdom C domain subtype classifications to date, as well as the discovery and experimental validation of novel conserved motifs with functional significance. Furthermore, our coevolution analysis revealed important barriers associated with re-engineering NRPSs and uncovered the entanglement between phylogeny and substrate specificity in NRPS sequences. Our findings provide a comprehensive and statistically insightful analysis of NRPS sequences, opening avenues for future data-driven discoveries.


Asunto(s)
Péptido Sintasas , Péptidos , Péptidos/química , Péptido Sintasas/genética , Péptido Sintasas/química , Péptido Sintasas/metabolismo
15.
Scand J Gastroenterol ; 59(1): 118-124, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37712446

RESUMEN

BACKGROUNDS AND AIMS: Magnetic resonance cholangiopancreatography (MRCP) plays a significant role in diagnosing common bile duct stones (CBDS). Currently, there are no studies to detect CBDS by using the deep learning (DL) model in MRCP. This study aimed to use the DL model You Only Look Once version 5 (YOLOv5) to diagnose CBDS in MRCP images and verify its validity compared to the accuracy of radiologists. METHODS: By collecting the thick-slab MRCP images of patients diagnosed with CBDS, 4 submodels of YOLOv5 were used to train and validate the performance. Precision, recall rate, and mean average precision (mAP) were used to evaluate model performance. Analyze possible reasons that may affect detection accuracy by validating MRCP images in 63 CBDS patients and comparing them with radiologist detection accuracy. Calculate the correctness of YOLOv5 for detecting one CBDS and multiple CBDS separately. RESULTS: The precision of YOLOv5l (0.970) was higher than that of YOLOv5x (0.909), YOLOv5m (0.874), and YOLOv5s (0.939). The mAP did not differ significantly between the 4 submodels, with the following results: YOLOv5l (0.942), YOLOv5x (0.947), YOLO5s (0.927), and YOLOv5m (0.946). However, in terms of training time, YOLOv5s was the fastest (4.8 h), detecting CBDS in only 7.2 milliseconds per image. In 63 patients the YOLOv5l model detected CBDS with an accuracy of 90.5% compared to 92.1% for radiologists, analyzing the difference between the positive group successfully identified and the unidentified negative group not. The incorporated variables include common bile duct diameter > 1 cm (p = .560), combined gallbladder stones (p = .706), maximum stone diameter (p = .057), combined cholangitis (p = .846), and combined pancreatitis (p = .656), and the number of CBDS (p = .415). When only one CBDS was present, the accuracy rate reached 94%. When multiple CBDSs were present, the recognition rate dropped to 70%. CONCLUSION: YOLOv5l is the model with the best results and is almost as accurate as the radiologist's detection of CBDS and is also capable of detecting the number of CBDS. Although the accuracy of the test gradually decreases as the number of stones increases, it can still be useful for the clinician's initial diagnosis.


Asunto(s)
Aprendizaje Profundo , Cálculos Biliares , Humanos , Pancreatocolangiografía por Resonancia Magnética , Colangiopancreatografia Retrógrada Endoscópica/métodos , Cálculos Biliares/diagnóstico por imagen , Conducto Colédoco , Estudios Retrospectivos
16.
Inorg Chem ; 63(1): 441-450, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38149999

RESUMEN

New amine-amino-bis(phenolate) ligands (H2LtBu and H2LCl) with a cyclic tertiary amine (pyrrolidine) as a side arm and tBu or Cl group on the phenolate ring have been prepared. The alkane elimination reaction between these free ligands and rare-earth tris(alkyl)s Ln(CH2SiMe3)3(THF)2 afforded the corresponding silylalkyl complexes LtBuLnCH2SiMe3(THF) (Ln = Y (1), Lu (2)) and LClYCH2SiMe3(THF) (3), where the solid-state structure of complex 1 was unambiguously confirmed by X-ray diffraction (XRD) analysis. These rare-earth metal complexes have been utilized as catalysts for the ring-opening polymerization (ROP) of biobased δ-caprolactone (δCL), either in the absence or presence of alcohols, to give poly(δ-caprolactone) (PδCL) with controlled molecular weight and narrow distribution (D < 1.2). The polymerization kinetics of δCL in toluene with yttrium complexes 1 and 3 were investigated. Oligomers prepared with complex 3 alone and the 3/PhCHMeOH binary catalyst system were well characterized with 1H NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS). Moreover, chemical recycling of the resultant PδCL was achieved with high yield in a solution at ambient temperature (>92%) or in bulk at 130 °C (>82%) by using commercial KOtBu as a promotor.

17.
Arch Virol ; 169(5): 96, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619633

RESUMEN

In recent years, the pig industry in Xinjiang, China, has been severely impacted by outbreaks of porcine epidemic diarrhea (PED), despite vaccination efforts. In this study, we investigated the genetic characteristics of currently prevalent porcine epidemic diarrhea virus (PEDV) strains in the region. We collected 548 samples from animals with suspected PED on large-scale pig farms in Xinjiang. Of these, 258 tested positive for PEDV by RT-PCR, yielding an overall positivity rate of 47.08%. S1 gene sequencing and phylogenetic analysis were conducted on 23 randomly selected RT-PCR-positive samples. Three endemic strains of PEDV (PEDV/CH/XU/2020, PEDV/CH/XK/2020, and PEDV/CH/XA/2020) were isolated, and their complete genome sequences were analyzed for evidence of genetic recombination. Sequence comparison of the S gene indicated significant variations in the S1 gene of the Xinjiang strains compared to the vaccine strains CV777, AJ1102, and LWL, with 90.2%-98.5% nucleotide sequence identity. Notably, both the N-terminal and C-terminal domains of the S protein showed significant variation. Genetic evolutionary analysis identified the GIIa subtype as the dominant genotype among the epidemic strains in Xinjiang. Recombination analysis revealed inter-subtype recombination events in the PEDV/CH/XK/2020 and XJ1904-34 strains. These findings highlight the extensive genetic variation in the predominant GIIa genotype of PEDV in Xinjiang, which does not match the genotype of the currently used vaccine strains. These data may guide further efforts toward the development of effective vaccines for the control of PED.


Asunto(s)
Disentería , Virus de la Diarrea Epidémica Porcina , Vacunas , Animales , Porcinos , Filogenia , Virus de la Diarrea Epidémica Porcina/genética , Evolución Biológica , China/epidemiología
18.
Clin Lab ; 70(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38469775

RESUMEN

BACKGROUND: The aim of this study was to verify the analytical performance of the UD90DT electrochemiluminescence immunoassay system (the UD90DT system) for measuring high-sensitivity cardiac troponin T (hs-cTnT). METHODS: According to the Clinical and Laboratory Standards Institute guidelines, the imprecision, linearity, reference interval, limit of blank (LoB), limit of detection (LoD), and functional sensitivity (FS) of hs-cTnT using the UD90DT system were verified. The trueness was validated using the Proficiency Testing (PT) materials. RESULTS: The within-run and between-run coefficients of variations (CVs) of two hs-cTnT levels were 7.2% and 1.5%, and 7.1% and 2.6%, respectively. The biases of the PT samples (n = 6) all fell within the allowable total error. The linearity satisfied the requirements, with a slope of 0.9963 and an R12 value of 0.9998. The hs-cTnT levels of the healthy volunteers (n = 20) ranged from 3.0 ng/L to 7.7 ng/L. All blank calibrator measurements (n = 20) fell within the LoD claim, and none of the samples (n = 25) had a LoB value ≤ 3.0 ng/L. The FS was 5.3 ng/L. Furthermore, a good correlation between the UD90DT system and the Cobas e 601 module was observed for hs-cTnT. CONCLUSIONS: The analytical performance of hs-cTnT using the UD90DT system is acceptable and satisfies clinical needs.


Asunto(s)
Pruebas Inmunológicas , Troponina T , Humanos , Límite de Detección , Inmunoensayo , Biomarcadores
19.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33431650

RESUMEN

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.


Asunto(s)
COVID-19 , Trazado de Contacto , Máscaras , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Humanos
20.
Biochem Genet ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753026

RESUMEN

The Stat (signal transducer and activator of transcription) gene family plays a vital role in regulating immunity and the processes of cellular proliferation, differentiation, and apoptosis across diverse organisms. Although the functions of Stat genes in immunity have been extensively documented in many mammals, limited data are available for reptiles. We used phylogenetic analysis to identify eight putative members of the Stat family (Stat1-1, Stat1-2, Stat2, Stat3, Stat4, Stat5b, Stat6-1, and Stat6-2) within the genome of M. reevesii, a freshwater turtle found in East Asia. Sequence analysis showed that the Stat genes contain four conserved structural domains protein interaction domain, coiled-coil domain, DNA-binding domain, and Src homology domain 2. In addition, Stat1, Stat2, and Stat6 contain TAZ2bind, Apolipo_F, and TALPID3 structural domains. The mRNA levels of Stat genes were upregulated in spleen tissues at 4, 8, 12, and 16 h after administration of lipopolysaccharide, a potent activator of the immune system. Stat5b expression at 12-h LPS post-injection exhibited the most substantial difference from the control. The expression of Stat5b in spleen tissue cellular was verified by immunofluorescence. These results suggest that Stat5b plays a role in the immune response of M. reevesii and may prove to be as a positive marker of an immune response in future studies.

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