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1.
Plant Cell ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941447

RESUMEN

Plants possess a robust and sophisticated innate immune system against pathogens and must balance growth with rapid pathogen detection and defense. The intracellular receptors with nucleotide-binding leucine-rich repeat (NLR) motifs recognize pathogen-derived effector proteins and thereby trigger the immune response. The expression of genes encoding NLR receptors is precisely controlled in multifaceted ways. The alternative splicing (AS) of introns in response to infection is recurrently observed but poorly understood. Here we report that the potato (Solanum tuberosum) NLR gene RB undergoes AS of its intron, resulting in two transcriptional isoforms, which coordinately regulate plant immunity and growth homeostasis. During normal growth, RB predominantly exists as intron-retained isoform RB_IR, encoding a truncated protein containing only the N-terminus of the NLR. Upon late blight infection, the pathogen induces intron splicing of RB, increasing the abundance of RB_CDS, which encodes a full-length and active R protein. By deploying the RB splicing isoforms fused with a luciferase reporter system, we identified IPI-O1 (also known as Avrblb1), the RB cognate effector, as a facilitator of RB AS. IPI-O1 directly interacts with potato splicing factor StCWC15, resulting in altered localization of StCWC15 from the nucleoplasm to the nucleolus and nuclear speckles. Mutations in IPI-O1 that eliminate StCWC15 binding also disrupt StCWC15 re-localization and RB intron splicing. Thus, our study reveals that StCWC15 serves as a surveillance facilitator that senses the pathogen-secreted effector and regulates the trade-off between RB-mediated plant immunity and growth, expanding our understanding of molecular plant-microbe interactions.

2.
PLoS Pathog ; 19(4): e1011346, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37083862

RESUMEN

Oomycetes are a group of filamentous microorganisms that include some of the biggest threats to food security and natural ecosystems. However, much of the molecular basis of the pathogenesis and the development in these organisms remains to be learned, largely due to shortage of efficient genetic manipulation methods. In this study, we developed modified transformation methods for two important oomycete species, Phytophthora infestans and Plasmopara viticola, that bring destructive damage in agricultural production. As part of the study, we established an improved Agrobacterium-mediated transformation (AMT) method by prokaryotic expression in Agrobacterium tumefaciens of AtVIP1 (VirE2-interacting protein 1), an Arabidopsis bZIP gene required for AMT but absent in oomycetes genomes. Using the new method, we achieved an increment in transformation efficiency in two P. infestans strains. We further obtained a positive GFP transformant of P. viticola using the modified AMT method. By combining this method with the CRISPR/Cas12a genome editing system, we successfully performed targeted mutagenesis and generated loss-of-function mutations in two P. infestans genes. We edited a MADS-box transcription factor-encoding gene and found that a homozygous mutation in MADS-box results in poor sporulation and significantly reduced virulence. Meanwhile, a single-copy avirulence effector-encoding gene Avr8 in P. infestans was targeted and the edited transformants were virulent on potato carrying the cognate resistance gene R8, suggesting that loss of Avr8 led to successful evasion of the host immune response by the pathogen. In summary, this study reports on a modified genetic transformation and genome editing system, providing a potential tool for accelerating molecular genetic studies not only in oomycetes, but also other microorganisms.


Asunto(s)
Ecosistema , Phytophthora infestans , Phytophthora infestans/genética , Agrobacterium tumefaciens/genética , Virulencia/genética , Mutación
3.
Cereb Cortex ; 34(1)2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-38037857

RESUMEN

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40 Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.


Asunto(s)
Enfermedad de Alzheimer , Sustancia Blanca , Humanos , Sustancia Gris/patología , Sustancia Blanca/patología , Estimulación Magnética Transcraneal , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/patología , Entrenamiento Cognitivo , Imagen por Resonancia Magnética/métodos , Encéfalo
4.
BMC Biol ; 22(1): 110, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38735918

RESUMEN

BACKGROUND: Plants differ more than threefold in seed oil contents (SOCs). Soybean (Glycine max), cotton (Gossypium hirsutum), rapeseed (Brassica napus), and sesame (Sesamum indicum) are four important oil crops with markedly different SOCs and fatty acid compositions. RESULTS: Compared to grain crops like maize and rice, expanded acyl-lipid metabolism genes and relatively higher expression levels of genes involved in seed oil synthesis (SOS) in the oil crops contributed to the oil accumulation in seeds. Here, we conducted comparative transcriptomics on oil crops with two different SOC materials. In common, DIHYDROLIPOAMIDE DEHYDROGENASE, STEAROYL-ACYL CARRIER PROTEIN DESATURASE, PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE, and oil-body protein genes were both differentially expressed between the high- and low-oil materials of each crop. By comparing functional components of SOS networks, we found that the strong correlations between genes in "glycolysis/gluconeogenesis" and "fatty acid synthesis" were conserved in both grain and oil crops, with PYRUVATE KINASE being the common factor affecting starch and lipid accumulation. Network alignment also found a conserved clique among oil crops affecting seed oil accumulation, which has been validated in Arabidopsis. Differently, secondary and protein metabolism affected oil synthesis to different degrees in different crops, and high SOC was due to less competition of the same precursors. The comparison of Arabidopsis mutants and wild type showed that CINNAMYL ALCOHOL DEHYDROGENASE 9, the conserved regulator we identified, was a factor resulting in different relative contents of lignins to oil in seeds. The interconnection of lipids and proteins was common but in different ways among crops, which partly led to differential oil production. CONCLUSIONS: This study goes beyond the observations made in studies of individual species to provide new insights into which genes and networks may be fundamental to seed oil accumulation from a multispecies perspective.


Asunto(s)
Productos Agrícolas , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Aceites de Plantas , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Aceites de Plantas/metabolismo , Perfilación de la Expresión Génica/métodos , Transcriptoma , Semillas/genética , Semillas/metabolismo , Regulación de la Expresión Génica de las Plantas
5.
Nano Lett ; 24(25): 7716-7723, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38848111

RESUMEN

Mixed-dimensional heterostructures integrate materials of diverse dimensions with unique electronic functionalities, providing a new platform for research in electron transport and optoelectronic detection. Here, we report a novel covalently bonded one-dimensional/two-dimensional (1D/2D) homojunction structure with robust junction contacts, which exhibits wide-spectrum (from the visible to near-infrared regions), self-driven photodetection, and polarization-sensitive photodetection capabilities. Benefiting from the ultralow dark current at zero bias voltage, the on/off ratio and detectivity of the device reach 1.5 × 103 and 3.24 × 109 Jones, respectively. Furthermore, the pronounced anisotropy of the WSe2 1D/2D homojunction is attributed to its low symmetry, enabling polarization-sensitive detection. In the absence of any external bias voltage, the device exhibits strong linear dichroism for wavelengths of 638 and 808 nm, with anisotropy ratios of 2.06 and 1.96, respectively. These results indicate that such mixed-dimensional structures can serve as attractive building blocks for novel optoelectronic detectors.

6.
Neuroimage ; 291: 120593, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38554780

RESUMEN

OBJECTIVE: The conventional methods for interpreting tau PET imaging in Alzheimer's disease (AD), including visual assessment and semi-quantitative analysis of fixed hallmark regions, are insensitive to detect individual small lesions because of the spatiotemporal neuropathology's heterogeneity. In this study, we proposed a latent feature-enhanced generative adversarial network model for the automatic extraction of individual brain tau deposition regions. METHODS: The latent feature-enhanced generative adversarial network we propose can learn the distribution characteristics of tau PET images of cognitively normal individuals and output the abnormal distribution regions of patients. This model was trained and validated using 1131 tau PET images from multiple centres (with distinct races, i.e., Caucasian and Mongoloid) with different tau PET ligands. The overall quality of synthetic imaging was evaluated using structural similarity (SSIM), peak signal to noise ratio (PSNR), and mean square error (MSE). The model was compared to the fixed templates method for diagnosing and predicting AD. RESULTS: The reconstructed images archived good quality, with SSIM = 0.967 ± 0.008, PSNR = 31.377 ± 3.633, and MSE = 0.0011 ± 0.0007 in the independent test set. The model showed higher classification accuracy (AUC = 0.843, 95 % CI = 0.796-0.890) and stronger correlation with clinical scales (r = 0.508, P < 0.0001). The model also achieved superior predictive performance in the survival analysis of cognitive decline, with a higher hazard ratio: 3.662, P < 0.001. INTERPRETATION: The LFGAN4Tau model presents a promising new approach for more accurate detection of individualized tau deposition. Its robustness across tracers and races makes it a potentially reliable diagnostic tool for AD in practice.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Proteínas tau/metabolismo , Encéfalo/metabolismo , Disfunción Cognitiva/patología , Tomografía de Emisión de Positrones/métodos
7.
Anal Chem ; 96(11): 4647-4656, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38441540

RESUMEN

Telomerase is a basic reverse transcriptase that maintains the telomere length in cells, and accurate and specific sensing of telomerase in living cells is critical for medical diagnostics and disease therapeutics. Herein, we demonstrate for the first time the construction of an enzymatically controlled DNA nanomachine with endogenous apurinic/apyrimidinic endonuclease 1 (APE1) as a driving force for one-step imaging of telomerase in living cells. The DNA nanomachine is designed by rational engineering of substrate probes and reporter probes embedded with an enzyme-activatable site (i.e., AP site) and their subsequent assembly on a gold nanoparticle (AuNP). Upon recognition and cleavage of the AP site in the substrate probe by APE1, the loop of the substrate probe unfolds, exposing telomeric primer (TP) with the 3'-OH end. Subsequently, the TP is elongated by telomerase at the 3'-OH end to generate a long telomeric product. The resultant telomeric product acts as a swing arm that can hybridize with a reporter probe to initiate the APE1-powered walking reaction, ultimately generating a significantly enhanced fluorescence signal. Notably, endogenous APE1 is used as the driving force of the DNA nanomachine, avoiding the introduction of exogenous auxiliary cofactors into the cellular microenvironment. Owing to the high kinetics and high amplification efficiency of the APE1-powered DNA nanomachine, this strategy enables one-step sensitive sensing of telomerase in vitro and in vivo. It can successfully discriminate telomerase activity between cancer cells and normal cells, screen telomerase inhibitors, and monitor the variations of telomerase activity in living cells, offering a prospective platform for molecular diagnostics and drug discovery.


Asunto(s)
Nanopartículas del Metal , Telomerasa , Humanos , Telomerasa/metabolismo , Oro/química , Nanopartículas del Metal/química , ADN/química , Células HeLa , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo
8.
Hum Brain Mapp ; 45(7): e26689, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38703095

RESUMEN

Tau pathology and its spatial propagation in Alzheimer's disease (AD) play crucial roles in the neurodegenerative cascade leading to dementia. However, the underlying mechanisms linking tau spreading to glucose metabolism remain elusive. To address this, we aimed to examine the association between pathologic tau aggregation, functional connectivity, and cascading glucose metabolism and further explore the underlying interplay mechanisms. In this prospective cohort study, we enrolled 79 participants with 18F-Florzolotau positron emission tomography (PET), 18F-fluorodeoxyglucose PET, resting-state functional, and anatomical magnetic resonance imaging (MRI) images in the hospital-based Shanghai Memory Study. We employed generalized linear regression and correlation analyses to assess the associations between Florzolotau accumulation, functional connectivity, and glucose metabolism in whole-brain and network-specific manners. Causal mediation analysis was used to evaluate whether functional connectivity mediates the association between pathologic tau and cascading glucose metabolism. We examined 22 normal controls and 57 patients with AD. In the AD group, functional connectivity was associated with Florzolotau covariance (ß = .837, r = 0.472, p < .001) and glucose covariance (ß = 1.01, r = 0.499, p < .001). Brain regions with higher tau accumulation tend to be connected to other regions with high tau accumulation through functional connectivity or metabolic connectivity. Mediation analyses further suggest that functional connectivity partially modulates the influence of tau accumulation on downstream glucose metabolism (mediation proportion: 49.9%). Pathologic tau may affect functionally connected neurons directly, triggering downstream glucose metabolism changes. This study sheds light on the intricate relationship between tau pathology, functional connectivity, and downstream glucose metabolism, providing critical insights into AD pathophysiology and potential therapeutic targets.


Asunto(s)
Enfermedad de Alzheimer , Fluorodesoxiglucosa F18 , Imagen por Resonancia Magnética , Red Nerviosa , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Masculino , Femenino , Anciano , Proteínas tau/metabolismo , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/metabolismo , Red Nerviosa/fisiopatología , Glucosa/metabolismo , Conectoma , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/fisiopatología , Anciano de 80 o más Años
9.
Hum Brain Mapp ; 45(4): e26647, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38488448

RESUMEN

Parkinson's disease (PD) patients exhibit deficits in primary sensorimotor and higher-order executive functions. The gradient reflects the functional spectrum in sensorimotor-associated areas of the brain. We aimed to determine whether the gradient is disrupted in PD patients and how this disruption is associated with treatment outcome. Seventy-six patients (mean age, 59.2 ± 12.4 years [standard deviation], 44 women) and 34 controls participants (mean age, 58.1 ± 10.0 years [standard deviation], 19 women) were evaluated. We explored functional and structural gradients in PD patients and control participants. Patients were followed during 2 weeks of multidisciplinary intensive rehabilitation therapy (MIRT). The Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) was administered to patients before and after treatment. We investigated PD-related alterations in the principal functional and structural gradients. We further used a support vector machine (SVM) and correlation analysis to assess the classification ability and treatment outcomes related to PD gradient alterations, respectively. The gradients showed significant differences between patients and control participants, mainly in somatosensory and visual networks involved in primary function, and higher-level association networks (dorsal attentional network (DAN) and default mode network (DMN)) related to motor control and execution. On the basis of the combined functional and structural gradient features of these networks, the SVM achieved an accuracy of 91.2% in discriminating patients from control participants. Treatment reduced the gradient difference. The altered gradient exhibited a significant correlation with motor improvement and was mainly distributed across the visual network, DAN and DMN. This study revealed damage to gradients in the brain characterized by sensorimotor and executive control deficits in PD patients. The application of gradient features to neurological disorders could lead to the development of potential diagnostic and treatment markers for PD.


Asunto(s)
Enfermedad de Parkinson , Corteza Sensoriomotora , Humanos , Femenino , Persona de Mediana Edad , Anciano , Imagen por Resonancia Magnética , Función Ejecutiva , Mapeo Encefálico
10.
Small ; 20(13): e2308688, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37946695

RESUMEN

Lymph node metastasis (LNM) is a significant barrier to the prognosis of patients with gastric cancer (GC). Helicobacter pylori (H. pylori)-positive GC patients experience a higher rate of LNM than H. pylori-negative GC patients. However, the underlying mechanism remains unclear. Based on the findings of this study, H. pylori-positive GC patients have greater lymphangiogenesis and lymph node immunosuppression than H. pylori-negative GC patients. In addition, miR-1246 is overexpressed in the plasma small extracellular vesicles (sEVs) of H. pylori-positive GC patients, indicating a poor prognosis. Functionally, sEVs derived from GC cells infected with H. pylori deliver miR-1246 to lymphatic endothelial cells (LECs) and promote lymphangiogenesis and lymphatic remodeling. Mechanistically, miR-1246 suppresses GSK3ß expression and promotes ß-Catenin and downstream MMP7 expression in LECs. miR-1246 also stabilizes programmed death ligand-1 (PD-L1) by suppressing GSK3ß and induces the apoptosis of CD8+ T cells. Overall, miR-1246 in plasma sEVs may be a novel biomarker and therapeutic target in GC-LNM.


Asunto(s)
Vesículas Extracelulares , Helicobacter pylori , MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Linfangiogénesis , Células Endoteliales/metabolismo , Linfocitos T CD8-positivos/metabolismo , Glucógeno Sintasa Quinasa 3 beta , MicroARNs/genética , Vesículas Extracelulares/metabolismo
11.
Small ; 20(2): e2304311, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37697695

RESUMEN

Due to the increased integration and miniaturization of electronic devices, traditional electronic packaging materials, such as epoxy resin (EP), cannot solve electromagnetic interference (EMI) in electronic devices. Thus, the development of multifunctional electronic packaging materials with superior electromagnetic wave absorption (EMA), high heat dissipation, and flame retardancy is critical for current demand. This study employs an in-situ growth method to load layered double hydroxides (LDH) onto transition metal carbides (MXene), synthesizing a novel composite material (MXene@LDH). MXene@LDH possesses a sandwich structure and exhibits excellent EMA performance, thermal conductivity, and flame retardancy. By adjusting the load of LDH, under the synergistic effect of multiple factors, such as dielectric and polarization losses, this work achieves an EMA material with a remarkable minimum reflection loss (RL) of -52.064 dB and a maximum effective absorption bandwidth (EAB) of 4.5 GHz. Furthermore, MXene@LDH emerges a bridging effect in EP, namely MXene@LDH/EP, leading to a 118.75% increase in thermal conductivity compared to EP. Simultaneously, MXene@LDH/EP contributes to the enhanced flame retardancy compared to EP, resulting in a 46.5% reduction in the total heat release (THR). In summary, this work provides a promising candidate advanced electronic packaging material for high-power density electronic packaging.

12.
Small ; 20(25): e2308724, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38229571

RESUMEN

In future information storage and processing, magnonics is one of the most promising candidates to replace traditional microelectronics. Yttrium iron garnet (YIG) films with perpendicular magnetic anisotropy (PMA) have aroused widespread interest in magnonics. Obtaining strong PMA in a thick YIG film with a small lattice mismatch (η) has been fascinating but challenging. Here, a novel strategy is proposed to reduce the required minimum strain value for producing PMA and increase the maximum thickness for maintaining PMA in YIG films by slight oxygen deficiency. Strong PMA is achieved in the YIG film with an η of only 0.4% and a film thickness up to 60 nm, representing the strongest PMA for such a small η reported so far. Combining transmission electron microscopy analyses, magnetic measurements, and a theoretical model, it is demonstrated that the enhancement of PMA physically originates from the reduction of saturation magnetization and the increase of magnetostriction coefficient induced by oxygen deficiency. The Gilbert damping values of the 60-nm-thick YIG films with PMA are on the order of 10-4. This strategy improves the flexibility for the practical applications of YIG-based magnonic devices and provides promising insights for the theoretical understanding and the experimental enhancement of PMA in garnet films.

13.
J Immunol ; 2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36426987

RESUMEN

The process of parturition is associated with inflammation within the uterine tissues, and IL-1ß is a key proinflammatory cytokine involved. Autophagy is emerging as an important pathway to remove redundant cellular components. However, it is not known whether IL-1ß employs the autophagy pathway to degrade collagen, thereby participating in membrane rupture at parturition. In this study, we investigated this issue in human amnion. Results showed that IL-1ß levels were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture, which was accompanied by decreased abundance of COL1A1 and COL1A2 protein but not their mRNA, the two components of collagen I. Consistently, IL-1ß treatment of cultured primary human amnion fibroblasts reduced COL1A1 and COL1A2 protein but not their mRNA abundance along with increased abundance of autophagy activation markers, including the microtubule-associated protein L chain 3ß II/I ratio and autophagy-related 7 (ATG7) in the cells. The reduction in COL1A1 and COL1A2 protein abundance induced by IL-1ß could be blocked by the lysosome inhibitor chloroquine or small interfering RNA-mediated knockdown of ATG7 or ER-phagy receptor FAM134C, suggesting that FAM134C-mediated ER-phagy was involved in IL-1ß-induced reduction in COL1A1 and COL1A2 protein in amnion fibroblasts. Consistently, levels of L chain 3ß II/I ratio, ATG7, and FAM134C were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture. Conclusively, increased IL-1ß abundance in human amnion may stimulate ER-phagy-mediated COL1A1 and COL1A2 protein degradation in amnion fibroblasts, thereby participating in membrane rupture at parturition.

14.
J Immunol ; 2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36288908

RESUMEN

The process of parturition is associated with inflammation within the uterine tissues, and IL-1ß is a key proinflammatory cytokine involved. Autophagy is emerging as an important pathway to remove redundant cellular components. However, it is not known whether IL-1ß employs the autophagy pathway to degrade collagen, thereby participating in membrane rupture at parturition. In this study, we investigated this issue in human amnion. Results showed that IL-1ß levels were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture, which was accompanied by decreased abundance of COL1A1 and COL1A2 protein but not their mRNA, the two components of collagen I. Consistently, IL-1ß treatment of cultured primary human amnion fibroblasts reduced COL1A1 and COL1A2 protein but not their mRNA abundance along with increased abundance of autophagy activation markers, including the microtubule-associated protein L chain 3ß II/I ratio and autophagy-related 7 (ATG7) in the cells. The reduction in COL1A1 and COL1A2 protein abundance induced by IL-1ß could be blocked by the lysosome inhibitor chloroquine or small interfering RNA-mediated knockdown of ATG7 or ER-phagy receptor FAM134C, suggesting that FAM134C-mediated ER-phagy was involved in IL-1ß-induced reduction in COL1A1 and COL1A2 protein in amnion fibroblasts. Consistently, levels of L chain 3ß II/I ratio, ATG7, and FAM134C were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture. Conclusively, increased IL-1ß abundance in human amnion may stimulate ER-phagy-mediated COL1A1 and COL1A2 protein degradation in amnion fibroblasts, thereby participating in membrane rupture at parturition.

15.
Childs Nerv Syst ; 40(7): 2245-2250, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38635073

RESUMEN

BACKGROUND: Craniopharyngioma is a common intracranial tumour in children. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Defects in pituitary function cause shortages of growth hormone, gonadotropin, corticotropin, thyrotropin, and vasopressin, resulting in short stature, delayed puberty, feebleness, lethargy, polyuria, etc. However, manifestations involving precocious puberty (PP) are rare. CASE REPORT: In both patients, surgical resection was performed after the diagnosis of craniopharyngioma, and breast development occurred postoperatively at one month in one patient and at one year and three months in the other patient. Central precocious puberty (CPP) was diagnosed via relevant examinations. Leuprorelin was injected subcutaneously every 28 days, and changes in height, weight, bone age, gonadal ultrasound and sex hormones were recorded. During the follow-up of the two children, the sex hormone levels were significantly reduced, and significant acceleration in bone age was not observed. CONCLUSIONS: CPP was induced by craniopharyngioma surgery, and treatment with gonadotropin-releasing hormone analogues (GnRHa) inhibited sexual development and bone age progression. More attention should be given to monitoring for CPP during long-term follow-up of craniopharyngiomas in the clinic.


Asunto(s)
Craneofaringioma , Neoplasias Hipofisarias , Pubertad Precoz , Humanos , Craneofaringioma/cirugía , Craneofaringioma/complicaciones , Leuprolida/uso terapéutico , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/complicaciones , Complicaciones Posoperatorias/etiología , Pubertad Precoz/etiología
16.
Nano Lett ; 23(4): 1424-1434, 2023 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-36779813

RESUMEN

Combination immunotherapy synergizing the PD-1 blockade with OX40 agonism has become a research hotspot, due to its enormous potential to overcome the restricted clinical objective response suffered by monotherapy. Questions of timing and sequence have been important aspects of immunotherapies when considering immunologic mechanisms; however, most of the time the straightforward additive approach was taken. Herein, our work is the first to investigate an alternative timing of aOX40 and aPD-1 treatment in melanoma-bearing mice, and it demonstrates that sequential administration (aOX40 first, then aPD-1 following) provided superior antitumor benefits than concurrent treatment. Based on that, to further avoid the limits suffered by solution forms, we adopted pharmaceutical technologies to construct an in situ-formed physical- and chemical-dually ROS-responsive nano-in-gel platform to implement sequential and prolonged release of aPD-1 and aOX40. Equipped with these advantages, the as-prepared (aPD-1NCs&aOX40)@Gels elicited augmented combination immunity and achieved great eradication of both primary and distant melanoma tumors in vivo.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Melanoma , Nanoestructuras , Animales , Ratones , Geles/química , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Especies Reactivas de Oxígeno , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Receptores OX40/antagonistas & inhibidores , Receptores OX40/inmunología
17.
J Environ Manage ; 356: 120600, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38547823

RESUMEN

The 'extreme' emission abatement during the lockdown (from the end of 2019 to the early 2020) provided an experimental period to investigate the corresponding source-specific effects of aerosol. In this study, the variations of source-specific light absorption (babs) and direct radiative effect (DRE) were obtained during and after the lockdown period by using the artificial neural network (ANN) and source apportionment environmental receptor model. The results showed that the babs decreased for all sources during the two periods. The most reductions were observed with ∼90% for traffic-related emissions (during the lockdown) and ∼85% for coal combustion (after the lockdown), respectively. Heightened babs (370 nm) values were obtained for coal and biomass burning during the lockdown, which was attributed to the enhanced atmospheric oxidization capacity. Nevertheless, the variations of babs (880 nm) after the lockdown was mainly due to the weakening of oxidation and reduced emissions of secondary precursors. The present study indicated that the large-scale emission reduction can promote both reductions of babs (370 nm) and DRE (34-68%) during the lockdown. The primary emissions decrease (e.g., Traffic emission) may enhance atmosphere oxidation, increase the ultraviolet wavelength light absorption and DRE efficiencies. The source-specific emission reduction may be contributed to various radiation effects, which is beneficial for the adopting of control strategies.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Carbón Mineral , Aerosoles/análisis , Biomasa , Material Particulado/análisis , China
18.
Prep Biochem Biotechnol ; 54(1): 103-114, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37184437

RESUMEN

Gamma-aminobutyric acid (GABA) is an vital neurotransmitter, and the reaction to obtain GABA through biocatalysis requires coenzymes, which are therefore limited in the production of GABA. In this study, polyacrylamide hydrogels doped with chitosan and waste toner were synthesized for glutamate decarboxylase (GAD) and coenzyme co-immobilization to realize the production of GABA and the recovery of coenzymes. Enzymatic properties of immobilized GAD were discussed. The immobilized enzymes have significantly improved pH and temperature tolerance compared to free enzymes. In terms of reusability, after 10 repeated reuses of the immobilized GAD, the residual enzyme activity of immobilized GAD still retains 100% of the initial enzyme activity, and the immobilized coenzyme can also be kept at about 32%, with better stability and reusability. And under the control of no exogenous pH, immobilized GAD showed good performance in producing GABA. Therefore, in many ways, the new composite hydrogel provides another way for the utilization of waste toner and promises the possibility of industrial production of GABA.


Asunto(s)
Quitosano , Glutamato Descarboxilasa/química , Ácido gamma-Aminobutírico , Coenzimas , Fenómenos Magnéticos
19.
Water Sci Technol ; 89(11): 2936-2950, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38877623

RESUMEN

Increasingly frequent urban floods strain the traditional grey infrastructure, overwhelming the capacity of drainage networks and causing challenges in managing stormwater. The heavy precipitation leads to flooding and damage to drainage systems. Consequently, efficient mitigation strategies for flooding have been researched deeply. Green infrastructure (GI) has proved to be effective in responding the increasing risk of flood and alleviate pressure on drainage systems. However, as the primary infrastructure of stormwater management, there is still a lack of attention to the dynamic operation feature of urban sewer systems during precipitation events. To fill this gap, we proposed a novel approach that integrates hydraulic characteristics and the topological structure of a sewer network system. This approach aims to identify influential nodes, which contribute to the connectivity of the sewer network amidst dynamic changes in inflow during precipitation events. Furthermore, we adopted rain barrels to serve as exemplars of GI, and 14 GI layout schemes are produced based on the different ranks of influential nodes. Implementing GI measures on both poorly performing and well-performing nodes can yield distinct benefits in mitigating node flooding. This approach provides a new perspective for stormwater management, establishing effective synergy between GI and the drainage system.


Asunto(s)
Drenaje de Agua , Inundaciones , Lluvia
20.
J Environ Sci (China) ; 138: 406-417, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38135406

RESUMEN

In this study, online water-soluble inorganic ions were detected to deduce the formation mechanism of secondary inorganic aerosol in Xianyang, China during wintertime. The dominant inorganic ions of sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+) (the sum of those is abbreviated as SNA) accounted for 17%, 21%, and 12% of PM2.5 mass, respectively. While the air quality deteriorated from excellent to poor grades, the precursor gas sulfur dioxide (SO2) of SO42- increased and then decreased with a fluctuation, while nitrogen dioxide (NO2) and ammonia (NH3), precursors of NO3- and NH4+, and SNA show increasing trends. Meteorological factors including boundary layer height (BLH), temperature, and wind speed also show decline trends, except relative humidity (RH). Meanwhile, the secondary conversion ratio shows a remarkable increasing trend, indicating that there was a strong secondary transformation. From the perspective of chemical mechanisms, RH is positively correlated with sulfur oxidation ratios (SOR), nitrogen oxidation ratios (NOR), and ammonia conversion ratios, representing that the increase of humidity could promote the generation of SNA. Notably, SOR and NOR were also positively related to the ammonia. On the one hand, the low wind speed and BLH led to the accumulation of pollutants. On the other hand, the increases of RH and ammonia promoted more formations of SNA and PM2.5. The results advance our identification of the contributors to the haze episodes and assist to establish more efficient emission controls in Xianyang, in addition to other cities with similar emission and geographical characteristics.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Amoníaco , Monitoreo del Ambiente , Estaciones del Año , China , Nitratos/análisis , Nitrógeno , Aerosoles/análisis
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