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This study aims to investigate the effects of the Galectin-3 (Gal-3) inhibitor TD139 on inflammation and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF-α, assessing Gal-3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post-delivery placental tissues were analyzed. Data were analyzed using one-way or two-way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF-α-induced increases in Gal-3, IL-1ß, IL-6, MCP-1, and ERK/JNK/p38 activation in placental tissues. In STZ-induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF-α, IL-1ß, IL-6, and MCP-1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF-α stimulated placental tissues and STZ-induced GDM mice, suggesting its therapeutic potential for managing GDM-related placental inflammation and improving pregnancy outcomes. The study used TNF-α to mimic GDM in placental tissues and an STZ-induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.
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We develop a general theory of Fermi polarons at nonzero temperature, including particle-hole excitations of the Fermi sea shakeup to arbitrarily high orders. The exact set of equations of the spectral function is derived by using both Chevy ansatz and diagrammatic approach, and their equivalence is clarified to hold in free space only, with an unregularized infinitesimal interaction strength. The correction to the polaron spectral function arising from two-particle-hole excitations is explicitly examined for an exemplary case of Fermi polarons in one-dimensional optical lattices. We find quantitative improvements at low temperatures with the inclusion of two-particle-hole excitations, in both polaron energies and decay rates. Our exact theory of Fermi polarons with arbitrary orders of particle-hole excitations might be used to better understand the intriguing polaron dynamical responses in two or three dimensions, whether in free space or within lattices.
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Correlated variability in the visual cortex is modulated by stimulus properties. The stimulus dependence of correlated variability impacts stimulus coding and is indicative of circuit structure. An affine model combining a multiplicative factor and an additive offset has been proposed to explain how correlated variability in primary visual cortex (V1) depends on stimulus orientations. However, whether the affine model could be extended to explain modulations by other stimulus variables or variability shared between two brain areas is unknown. Motivated by a simple neural circuit mechanism, we modified the affine model to better explain the contrast dependence of neural variability shared within either primary or secondary visual cortex (V1 or V2) as well as the orientation dependence of neural variability shared between V1 and V2. Our results bridge neural circuit mechanisms and statistical models and provide a parsimonious explanation for the stimulus dependence of correlated variability within and between visual areas.
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Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M.bambusae sp. nov. and Microdochiumaustrale sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochiumsinense has been collected from diseased leaves of Phragmitesaustralis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided.
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Chronic kidney disease (CKD) has emerged as a significant public health concern. In this article, we investigated the mechanism of oat dietary fiber in regulating CKD. Our findings indicated that the gut microbiota of CKD patients promoted gut microbiota dysbiosis and kidney injury in CKD mice. Intervention with oat-resistant starch prepared by ultrasonic combined enzymatic hydrolysis (ORSU) and oat ß-glucan with a molecular weight of 5 × 104 Da (OBGM) elevated the levels of short-chain fatty acids (SCFAs) and regulated gut dysbiosis in the gut-humanized CKD mice. ORSU and OBGM also reduced CKD-related uremic toxins such as creatinine, indoxyl sulfate (IS), and p-cresol sulfate (PCS) levels; reinforced the intestinal barrier function of the gut-humanized CKD mice; and mitigated renal inflammation and fibrosis via the NF-κB/TGF-ß pathway. Therefore, ORSU and OBGM might delay the progression of CKD by modulating the gut microbiota to reduce uremic toxins levels. Our results explain the mechanism of oat dietary fiber aimed at mitigating CKD.
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A five-step phase shift demodulation scheme based on a multiwavelength averaging method is proposed to suppress crosstalk within an extrinsic Fabry-Perot interferometric (EFPI) sensor array. The paper focuses on a two-element sensing system based on the EFPI sensors to investigate the crosstalk in the EFPI sensor array. A detailed theoretical analysis of crosstalk suppression using the proposed demodulation method is presented. Numerical simulations and experiments are put forward to demonstrate the effectiveness of the proposed demodulation scheme in suppressing crosstalk under varying parameters. The results of the multiwavelength demodulation scheme indicate superior crosstalk suppression capability in contrast to the conventional five-step phase shift demodulation scheme based on a single-wavelength demodulation method. Furthermore, the paper reveals the enhanced crosstalk suppression capability of the proposed demodulation scheme when the cavity length difference between elements is not equal to zero. It alleviates the requirement for consistent cavity length among different elements in the sensing array. The proposed demodulation scheme exhibits excellent crosstalk suppression capabilities in optical multiplexing arrays by decreasing the dependency on extinction ratio and could be potentially used in the large-scale optical hydrophone array system.
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Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection.
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【Objective】 To analyze the clinical characteristics of serum vitamin K2 in children and its correlation with bone mineral density, so as to provide reference for the prevention of insufficient bone strength in children. 【Methods】 A total of 4 145 children who underwent serum vitamin K2 testing and physical examination at pediatric outpatient clinics of several municipal and county hospitals in Chongqing from January 2020 to March 2023 were retrospectively selected into this study for serum vitamin K2-related analysis.Further 844 school-age children who completed serum 25-(OH)D and lumbar bone densitometry measurements were screened to analyze the correlation between vitamin K2level and bone mineral density 【Results】 The overall serum vitamin K2 deficiency rate was 61.6% (2 553/4 145), and the difference in serum vitamin K2 deficiency rate between different age groups was statistically significant (χ2=39.364, P<0.05).The vitamin K2 level of children was significantly influenced by season and maternal education level (χ2=45.310,9.990, P<0.05).There were significant differences in age (Z=3.416), gender (χ2=9.218) and serum vitamin K2 deficiency rate (χ2=5.826) between normal bone mass development group and insufficient bone mass development group (P<0.05).Multivariate Logistic regression analysis suggested that vitamin K2 deficiency was an independent risk factor for insufficient bone mass development in school-age children (OR=1.37,95%CI:1.03 - 1.83, P=0.030). 【Conclusions】 There is a higher serum vitamin K2 deficiency rate among children, especially infants and school-age children.Decreased bone mineral density in school-age children may be associated with serum vitamin K2 deficiency.
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Metastasis is the main cause of colorectal cancer (CRC)-related death, and the 5-year relative survival rate for CRC patients with distant metastasis is only 14%. X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a zinc-rich protein belonging to the interferon (IFN)-induced gene family. Here, we report a metastasis-promoting role of XAF1 in CRC by acting as a novel adaptor of valosin-containing protein (VCP). XAF1 facilitates VCP-mediated deubiquitination of the E3 ligase RING finger protein 114 (RNF114), which promotes K48-linked ubiquitination and subsequent degradation of junction plakoglobin (JUP). The XAF1-VCP-RNF114-JUP axis is critical for the migration and metastasis of CRC cells. Moreover, we observe correlations between the protein levels of XAF1, RNF114, and JUP in clinical samples. Collectively, our findings reveal an oncogenic function of XAF1 in mCRC and suggest that the XAF1-VCP-RNF114-JUP axis is a potential therapeutic target for CRC treatment.
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Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Colorretais/genética , gama Catenina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína com Valosina/genética , Proteína com Valosina/metabolismoRESUMO
Atmospheric ammonia has great environmental implications due to its important role in ecosystem and nitrogen cycle, as well as contribution to formation of secondary particles. China is recognized as a hotspot of NH3 pollution owing to agricultural and livestock intensification. In the quest to achieve a comprehensive understanding of atmospheric ammonia load and to quantify its environmental impacts in China, relying solely either on existing measurements or on model simulations falls short. Their limitations, either in spatial coverage and integrity or in data quality, fails to meet the needs. Available reanalysis products exhibit a marked deficiency in ammonia data. We therefore aim to propose an integrated ammonia reanalysis product in China, adeptly melding satellite observations from the Infrared Atmospheric Sounding Interferometer (IASI) NH3 retrievals with chemical transport model simulation, capitalizing on the robust Ensemble Kalman Filter (EnKF) data assimilation methodology. The product is validated in high quality via the comparison against independent measurements from ground monitoring stations. Spanning a decade from 2013 to 2022, our reanalysis uncovers not just the spatial intricacies of NH3 concentrations but also their temporal dynamics. Our findings pinpointed the spatial disparities in atmospheric ammonia intensities, highlighting regional hotspots in the NCP, SCB, and Northeast China, and identified annual and seasonal patterns. Our research provides crucial insights for shaping future NH3 pollution prevention and control strategies in China.
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Reservoir computing (RC), a variant recurrent neural network, has very compact architecture and ability to efficiently reconstruct nonlinear dynamics by combining both memory capacity and nonlinear transformations. However, in the standard RC framework, there is a trade-off between memory capacity and nonlinear mapping, which limits its ability to handle complex tasks with long-term dependencies. To overcome this limitation, this paper proposes a new RC framework called neural delayed reservoir computing (ND-RC) with a chain structure reservoir that can decouple the memory capacity and nonlinearity, allowing for independent tuning of them, respectively. The proposed ND-RC model offers a promising solution to the memory-nonlinearity trade-off problem in RC and provides a more flexible and effective approach for modeling complex nonlinear systems with long-term dependencies. The proposed ND-RC framework is validated with typical benchmark nonlinear systems and is particularly successful in reconstructing and predicting the Mackey-Glass system with high time delays. The memory-nonlinearity decoupling ability is further confirmed by several standard tests.
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IMPORTANCE: Distoseptispora as a single genus in Distoseptisporaceae was introduced by morphological and phylogenetic analyses. Members of this genus occur mainly as asexual morphs, forming effuse, hairy colonies on decaying wood, plant stems, bamboo culms, and fallen leaves and shafts in terrestrial and freshwater habitats. In the present study, saprobic hyphomycetes from plant debris were investigated, and eight new Distoseptispora species were introduced based on morphology and phylogenetic analyses of LSU, ITS, TEF1, and RPB2 sequence data. This study provides important data on the species diversity, ecological environment, and geographical area of Distoseptispora, greatly updates the classification of Distoseptispora, and improves our understanding of the taxonomy of Distoseptispora.
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Ascomicetos , Filogenia , China , Meio Ambiente , Água DoceRESUMO
A practical and metal-free approach for the regioselective selenation of chromones employing Selectfluor reagent under mild conditions is described. The developed method is suitable for a wide substrate scope and affords 3-selenylated chromones in good to excellent yield with high selectivity. An ionic mechanism is proposed for this transformation. Furthermore, the application of potassium thiocyanate with enaminones for the synthesis of thiocyano chromones in this transformation is also successful.
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Background: Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation. Methods: Sixty H22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer. Results: T cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (p < 0.001), with a significant increase of TNF-α (p < 0.001) and IFN-γ secretion (p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand+ and perforin+ tumor-infiltrating lymphocytes (TILs) and apoptotic H22 tumor cells were significantly higher (p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand+ TILs (r = 0.9145, p < 0.001) and perforin+ TILs (r = 0.9619, p < 0.001). Conclusion: T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.
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Imunoterapia Adotiva , Linfócitos T Citotóxicos , Camundongos , Animais , Proteína Ligante Fas , Perforina , Imunidade CelularRESUMO
Preeclampsia (PE) and gestational diabetes mellitus (GDM) are pregnancy-specific complications, which affect maternal health and fetal outcomes. Currently, clinical and pathological studies have shown that placenta homeostasis is affected by these two maternal diseases. In this study, we aimed to gain insight into the heterogeneous changes in cell types in placental tissue-isolated from cesarean section by single-cell sequencing, including those patients diagnosed with PE (n = 5), GDM (n = 5) and healthy control (n = 5). A total of 96,048 cells (PE: 31,672; GDM: 25,294; control: 39,082) were identified in six cell types, dominated by trophoblast cells and immune cells. In addition, trophoblast cells were divided into four subtypes, including cytotrophoblast cells (CTBs), villous cytotrophoblasts (VCTs), syncytiotrophoblast (STB), and extravillous trophoblasts (EVTs). Immune cells are divided into lymphocytes and macrophages, of which macrophages have 3 subtypes (decidual macrophages, Hofbauer cells and macrophages), and lymphocytes have 4 subtypes (BloodNK, T cells, plasma cells, and decidual natural killer cells). Meanwhile, we also proved the orderly differentiation sequence of CTB into VCT, then STB and EVT. By pair-wise analysis of the expression and enrichment of differentially expressed genes in trophoblast cells between PE, GDM and control, it was found that these cells were involved in immune, nutrient transfer, hormone and oxidative stress pathways. In addition, T cells and macrophages play an immune defense role in both PE and GDM. The proportion of CTB and EVT cells in placental tissue was confirmed by flow cytometry. Taken together, our results suggested that the human placenta is a dynamic heterogenous organ dominated by trophoblast and immune cells, which perform their respective roles and interact with other cells in the environment to maintain normal placental function.
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Diabetes Gestacional , Pré-Eclâmpsia , Humanos , Gravidez , Feminino , Placenta/metabolismo , Diabetes Gestacional/metabolismo , Pré-Eclâmpsia/metabolismo , Cesárea , Trofoblastos/metabolismo , Células Matadoras NaturaisRESUMO
Anesthetics, which include both local and general varieties, are a unique class of drugs widely utilized in clinical surgery to alleviate pain and promote relaxation in patients. Although numerous anesthetics and their traditional formulations are available in the market, only a select few exhibit excellent anesthetic properties that meet clinical requirements. The main challenges are the potential toxic and adverse effects of anesthetics, as well as the presence of the blood-brain barrier (BBB), which makes it difficult for most general anesthetics to effectively penetrate to the brain. Loading anesthetics onto nanocarriers as anesthetic nanomedicines might address these challenges and improve anesthesia effectiveness, reduce toxic and adverse effects, while significantly enhance the efficiency of general anesthetics passing through the BBB. Consequently, anesthetic nanomedicines play a crucial role in the field of anesthesia. Despite their significance, research on anesthetic nanomedicines is still in its infancy, especially when compared to other types of nanomedicines in terms of depth and breadth. Although local anesthetic nanomedicines have received considerable attention and essentially meet clinical needs, there are few reported instances of nanomedicines for general anesthetics. Given the extensive usage of anesthetics and the many of them need for improved performance, emerging anesthetic nanomedicines face both unparalleled opportunities and considerable challenges in terms of theory and technology. Thus, a comprehensive summary with systematic analyses of anesthetic nanomedicines is urgently required. This review provides a comprehensive summary of the classification, properties, and research status of anesthetic nanomedicines, along with an exploration of their opportunities and challenges. In addition, future research directions and development prospects are discussed. It is hoped that researchers from diverse disciplines will collaborate to study anesthetic nanomedicines and develop them as a valuable anesthetic dosage form for clinical surgery.
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Anestesia , Anestésicos Gerais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Nanomedicina , Anestésicos Locais , EncéfaloRESUMO
BACKGROUND: RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive. METHODS: RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis. RESULTS: RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2. CONCLUSION: Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC.
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Neoplasias Colorretais , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Fator de Transcrição STAT3/metabolismo , Hibridização in Situ Fluorescente , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , RNA , Proliferação de Células , Chaperonas Moleculares/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Movimento Celular/genética , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismoRESUMO
A new goal-systems model is proposed to help explain when individuals will protect themselves against the risks inherent to social connection. This model assumes that people satisfy the goal to feel included in safe social connections-connections where they are valued and protected rather than at risk of being harmed-by devaluing rejecting friends, trusting in expectancy-consistent relationships, and avoiding infectious strangers. In the hypothesized goal system, frustrating the fundamental goal to feel safe in social connection sensitizes regulatory systems that afford safety from the risk of being interpersonally rejected (i.e., the risk-regulation system), existentially uncertain (i.e., the social-safety system), or physically infected (i.e., the behavioral-immune system). Conversely, fulfilling the fundamental goal to feel safe in social connection desensitizes these self-protective systems. A 3-week experimental daily diary study (N = 555) tested the model hypotheses. We intervened to fulfill the goal to feel safe in social connection by repeatedly conditioning experimental participants to associate their romantic partners with highly positive, approachable words and images. We then tracked how vigilantly experimental versus control participants protected themselves when they encountered social rejection, unexpected behavior, or contagious illness in everyday life. Multilevel analyses revealed that the intervention lessoned self-protective defenses against each of these risks for participants who ordinarily felt most vulnerable to them. The findings provide the first evidence that the fundamental goal to feel safe in social connection can co-opt the risk-regulation, social-safety, and behavioral-immune systems as independent means for its pursuit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).