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OBJECTIVES: Utilizing RBC or PLT-related parameters to establish rules for the PLT-O reflex test can assist laboratories in quickly identifying specimens with interfered PLT-I that require PLT-O retesting. METHODS: Prospective PLT-I and PLT-O testing was performed on 6857 EDTA-anticoagulated whole blood samples, split randomly into training and validation cohorts at a 2:3 ratio. Reflex and non-reflex groups were distinguished based on the differences between PLT-I and PLT-O results. By comparing RBC and PLT parameter differences and flags in the training set, we pinpointed factors linked to PLT-O reflex testing. Utilizing Lasso regression, then refining through univariate and multivariate logistic regression, candidate parameters were selected. A predictive nomogram was constructed from these parameters and subsequently validated using the validation set. ROC curves were also plotted. RESULTS: Significant differences were observed between the reflex and non-reflex groups for 19 parameters including RBC, MCV, MCH, MCHC, RDW-CV, RDW-SD, Micro-RBC#, Micro-RBC%, Macro-RBC#, Macro-RBC%, MPV, PCT, P-LCC, P-LCR, PLR,"PLT clumps?" flag, "PLT abnormal histogram" flag, "IDA Anemia?" flag, and "RBC abnormal histogram" flag. After further analysis, Micro-RBC#, Macro-RBC%,"PLT clumps?", and "PLT abnormal histogram" flag were identified as candidate parameters to develop a nomogram with an AUC of 0.636 (95â¯%CI: 0.622-0.650), sensitivity of 42.9â¯% (95â¯%CI: 37.8-48.1â¯%), and specificity of 90.5â¯% (95â¯%C1: 89.6-91.3â¯%). CONCLUSIONS: The established rules may help laboratories improve efficiency and increase accuracy in determining platelet counts as a supplement to ICSH41 guidelines.
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Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in aquaculture. In this study, virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target antigen. Pichia pastoris constitutive secretory expression NTaer (GS115-NTaer) was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish immunity. The result shows that vaccination of GS115- NTaer for four weeks did not affect the growth performance of the host, while eliciting an effective immune protective response. Compared with the control group, the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α (TJP1α) gene, and significantly increased the contents of lysozyme (LYZ), complement C3 and C4 in the gut, indicating that the innate immune response of the fish was activated. The relative gene expression levels of macrophage-expressed gene 1 (MPEG1) and T cell receptor (TCR-α) in the gut, and MPEG1, CD4, CD8, TCR-α, GATA3, and T-bet in the spleen were all increased significantly, indicating that the cellular immune response of the fish was activated. Furthermore, the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased, which showed that humoral immunity was also activated. Moreover, inoculation with GS115-NTaer significantly changed the structure of gut microbiota. In particular, the relative ratio of (Firmicutes + Fusobacteriota + Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 groups. Lastly, the vaccinated fish were challenged with A. veronii, and the relative percent survival of GS115 and the GS115-NTear groups was 14.28% and 33.43%. This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish model. Collectively, this study provides information on the effectiveness of GS115-NTear as an oral vaccine for the green prevention and control of A. veronii infection in fish aquaculture.
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Environmental-friendless and high-performance thermoelectrics play a significant role in exploring sustainable clean energy. Among them, AgSbTe2 thermoelectrics, benefiting from the disorder in the cation sublattice and interface scattering from secondary phases of Ag2Te and Sb2Te3, exhibit low thermal conductivity and a maximum figure-of-merit ZT of 2.6 at 573 K via optimizing electrical properties and addressing phase transition issues. Therefore, AgSbTe2 shows considerable potential as a promising medium-temperature thermoelectric material. Additionally, with the increasing demands for device integration and portability in the information age, the research on flexible and wearable AgSbTe2 thermoelectrics aligns with contemporary development needs, leading to a growing number of research findings. This work provides a detailed and timely review of AgSbTe2-based thermoelectrics from materials to devices. Principles and performance optimization strategies are highlighted for the thermoelectric performance enhancement in AgSbTe2. The current challenges and future research directions of AgSbTe2-based thermoelectrics are pointed out. This review will guide the development of high-performance AgSbTe2-based thermoelectrics for practical applications.
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BACKGROUND: For several decades, it has been recognized that overactivation of the glutamate-gated N-methyl-D-aspartate receptors (NMDARs) and subsequent Ca2+ toxicity play a critical role in ischemic brain injury. 24S-hydroxycholesterol (24S-HC) is a major cholesterol metabolite in the brain, which has been identified as a potent positive allosteric modulator of NMDAR in rat hippocampal neurons. We hypothesize that 24S-HC worsens ischemic brain injury via its potentiation of the NMDAR, and reducing the production of 24S-HC by targeting its synthetic enzyme CYP46A1 provides neuroprotection. METHODS: We tested this hypothesis using electrophysiological, pharmacological, and transgenic approaches and in vitro and in vivo cerebral ischemia models. RESULTS: Our data show that 24S-HC potentiates NMDAR activation in primary cultured mouse cortical neurons in a concentration-dependent manner. At 10 µmol/L, it dramatically increases the steady-state currents by 51% and slightly increases the peak currents by 20%. Furthermore, 24S-HC increases NMDA and oxygen-glucose deprivation-induced cortical neuronal injury. The increased neuronal injury is largely abolished by NMDAR channel blocker MK-801, suggesting an NMDAR-dependent mechanism. Pharmacological inhibition of CYP46A1 by voriconazole or gene knockout of Cyp46a1 dramatically reduces ischemic brain injury. CONCLUSIONS: These results identify a new mechanism and signaling cascade that critically impacts stroke outcome: CYP46A1 â 24S-HC â NMDAR â ischemic brain injury. They offer proof of principle for further development of new strategies for stroke intervention by targeting CYP46A1 or its metabolite 24S-HC.
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BACKGROUND AND PURPOSE: This study aimed to investigate the risk factors for recurrent laryngeal nerve (RLN) injury after microwave ablation (MWA) of thyroid nodules and to identify factors influencing the recovery time of post-procedure hoarseness. MATERIALS AND METHODS: We retrospectively analyzed data from patients who underwent MWA for thyroid nodules at five hospitals between November 2018 and July 2022. Patients were divided into malignant and benign nodule groups. Variables analyzed included nodule size and location, the shortest distance from nodules to the thyroid capsule and tracheoesophageal groove (TEG-D), and ablation parameters. Univariate and multivariate analyses were performed to identify risk factors. Kaplan-Meier and Cox analyses were used to evaluate the recovery time of hoarseness after MWA. RESULTS: The study included 1,216 patients (mean age 44⯱â¯12 [SD] years; 901 women) with 602 malignant nodules and 614 benign nodules. The posterior capsule distance (PCD) and TEG-D were identified as independent influencing factors for hoarseness in all patients (Pâ¯=â¯0.014, ORâ¯=â¯0.068; Pâ¯<â¯0.001, ORâ¯=â¯0.005; AUCâ¯=â¯0.869). TEG-D was a significant risk factor for hoarseness, with safe thresholds identified at 4.9â¯mm for malignant nodules and 2.2â¯mm for benign nodules. Among patients who developed hoarseness, those in the close-distance group (TEG-D≤2 mm) had a longer recovery time compared to the distant-distance group. TEG-D was an independent factor influencing recovery time (Pâ¯=â¯0.008, HRâ¯=â¯11.204). CONCLUSION: Clinicians should consider several factors, particularly TEG-D and PCD, when assessing the risk of RLN injury before MWA. TEG-D was a vital independent factor influencing recovery time. SUMMARY: Clinicians should pay attention to several influencing factors for RLN injury before MWA and TEG-D was an independent influencing factor for recovery time of hoarseness after MWA.
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Viral diseases pose a significant threat to livestock husbandry and plant cultivation. CRISPR/Cas9-mediated targeted editing of viral genes offers a promising approach to antiviral therapy. The silkworm, Bombyx mori, is an economically important insect susceptible to infection by B. mori nucleopolyhedrovirus (BmNPV), and viral outbreaks cause severe economic losses to the sericulture industry. Here, we identified BmNPV orf76 as a viral late gene that is highly similar to Autographa californica multiple nucleopolyhedrovirus Ac93. The deletion of orf76 abolished BmNPV proliferation and hindered the production of infectious budded viruses. We generated a transgenic line, Cas9(+)/sgorf76(+), that did not affect the growth or development of the silkworm and demonstrated that the transgenic line Cas9(+)/sgorf76(+) efficiently cleaved orf76 at the sgorf76 site, resulting in large deletions at 120 h post-infection, with no observed off-target effects. Survival analyses revealed that the transgenic line Cas9(+)/sgorf76(+) exhibited significantly higher survival rates than the control lines Cas9(-)/sgorf76(-), regardless of the BmNPV inoculation dose. Additionally, the number of BmNPV DNA copies and the expression levels of viral genes were markedly inhibited in the transgenic line Cas9(+)/sgorf76(+) compared with the control line Cas9(-)/sgorf76(-). The results provide a promising target for Cas9-mediated antiviral therapy against BmNPV, and the findings provide new insights for baculovirus gene function studies and lepidopteran pest control.
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In the last decades, 4-nitrophenol is regarded as one of highly toxic organic pollutants in industrial wastewater, which attracts great concern to earth sustainability. Herein, atomically dispersed ternary FeCoNb active sites were incorporated into nitrogen-doped honeycomb-like mesoporous carbon (termed FeCoNb/NHC) by a two-step pyrolysis strategy, whose morphology, structure and size were characterized by a set of techniques. Further, the catalytic activity and reusability of the as-prepared FeCoNb/NHC were rigorously examined by using 4-NP catalytic hydrogenation as a proof-of-concept model. The influence of the secondary pyrolysis temperature on the catalytic performance was investigated, combined by illuminating the catalytic mechanism. The resultant catalyst exhibited significantly enhanced catalytic features with a normalized rate constant (kapp) of 1.2 × 104 min-1g-1 and superior stability, surpassing the home-made catalysts in the control groups and earlier research. This study provides some constructive insights for preparation of high-efficiency and cost-effectiveness single-atom nanocatalysts in organic pollutants environmental remediation.
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Acute myeloid leukaemia (AML) is a common and highly aggressive haematological malignancy in adults. Senescence-associated secretory phenotype (SASP) plays important roles in tumorigenesis and progression of tumour. However, the prognostic value of SASP in patients with AML has not been clarified. The present study aims to explore the prognostic value of SASP and develop a prognostic risk signature for AML. The RNA-sequencing data was collected from the TCGA, GTEx and TARGET databases. Subsequently, differentially expressed gene analysis, univariate Cox regression and LASSO regression were applied to identified prognostic SASP-related genes and construct a prognostic risk-scoring model. The risk score of each patient were calculated and patients were divided into high- or low-risk groups by the median risk score. This novel prognostic signature included 11 genes: G6PD, CDK4, RPS6KA1, UBC, H2BC12, KIR2DL4, HSF1, IFIT3, PIM1, RUNX3 and TRIM21. The patients with AML in the high-risk group had shorter OS, demonstrating that the risk score acted as a prognostic predictor, which was validated in the TAGET-AML dataset. Univariate and multivariate analysis revealed the risk score was an independent prognostic factor in patients with AML. Furthermore, the present study revealed that the risk score was associated with immune landscape, immune checkpoint gene expression and chemotherapeutic efficacy. In the present study, we constructed and validated a unique SASP-related prognostic model to assess therapeutic effect and prognosis in patients with AML, which might contribute to understanding the role of SASP in AML and guiding the treatment for AML.
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Biomarcadores de Tumor , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/mortalidad , Pronóstico , Femenino , Biomarcadores de Tumor/genética , Masculino , Perfilación de la Expresión Génica , Persona de Mediana Edad , Regulación Leucémica de la Expresión Génica , Transcriptoma/genética , Adulto , Factores de RiesgoRESUMEN
Background: Wound healing has always been a serious issue for doctors and primary health care systems. In addition, adipose stem cell-derived exosomes have been proven to play a positive and effective role in tissue repair and regeneration. A systematic review of these preclinical studies was performed to assess the efficacy of adipose stem cell-derived exosomes (ADSC-Exos) in treating wounds. This article aimed to study the effectiveness of ADSC-Exos for the treatment of animal skin wounds and includes a meta-analysis of exosomes from general wounds and diabetic ulcer wounds in in vitro models of animals to provide a theoretical basis for clinical translation. Methods: A total of 19 studies with 356 animals were identified by searching the PubMed, Cochrane, MEDLINE Complete, Web of Science, CNKI and Wanfang databases from inception to 15 November 2022. No language or time restrictions were applied. Stata17 was used for all the data analyses. Results: The meta-analysis showed that ADSC-Exo therapy significantly improved the wound healing rate in the control group, except in the diabetes group on day 7. Day 7 of general wounds [standard mean difference (SMD) 2.87, 95% confidence interval (CI) 1.91-3.83)] and day 14 (SMD 2.89, 95%CI 1.47-4.30). Day 14 (SMD 3.43, 95%CI 1.28-5.58) of diabetic wounds. Other outcomes, such as blood vessel density, collagen deposition and wound re-epithelization, improved with the administration of ADSC-Exos. Conclusions: A meta-analysis showed that ADSC-Exo therapy applied to general and diabetic wounds can promote neovascularization, improve epithelization and collagen fiber deposition, promote healing, and reduce scar formation. ADSC-Exos have broad potential in preclinical research and clinical fields.
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The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionalized methoxypoly(ethylene glycol), which exhibit exceptional single-particle brightness and excellent free diffusion capability in the ECS of brain tissues. Tracking single RGNs in acute brain slices allowed us to dynamically map spatial organizational features and redox levels within the ECS of brain tissues in disease models. This provides a powerful super-resolution imaging method that offers a potential opportunity to study the dynamic changes in the ECS microenvironment and to understand the physiological and pathological roles of the ECS in vivo.
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Encéfalo , Espacio Extracelular , Glutatión , Nanopartículas , Oxidación-Reducción , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Animales , Espacio Extracelular/metabolismo , Espacio Extracelular/química , Glutatión/química , Glutatión/metabolismo , Nanopartículas/química , Ratones , Polietilenglicoles/químicaRESUMEN
We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.
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Aprendizaje Profundo , Recurrencia Local de Neoplasia , Neoplasias Vesicales sin Invasión Muscular , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Neoplasias Vesicales sin Invasión Muscular/patología , Curva ROC , Medición de Riesgo/métodosRESUMEN
This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.
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Our previous study has shown that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exo) alleviated burn-induced acute lung injury (ALI). In this study, we explored a novel mechanism by which hUCMSCs-exo contributed to the inhibition of burn-induced ALI. The ALI rat model with severe burn was established for the in vivo experiments, and rats PMVECs were stimulated with the serum from burn-induced ALI rats for the in vitro experiments. The pathological changes of lung tissues were evaluated by HE staining; the cell viability was measured using CCK-8; the iron level and Fe2+ concentration were assessed using Iron Assay Kit and Fe2+ fluorescence detection probe; the mRNA expression of SLC7A11 and GPX4 were measured by qRT-PCR; the protein levels of SLC7A11, GPX4, Nrf2 and HO-1 were detected by western blot. Both the in vivo and in vitro experiments revealed that ferroptosis was significantly induced in burn-induced ALI, which as verified by increased iron level and Fe2+ concentration, and decreased SLC7A11 and GPX4 mRNA and protein levels. Furthermore, both hUCMSCs-exo and Fer-1 (the inhibitor of ferroptosis) alleviated lung inflammation and up-regulated protein levels of Nrf2 and HO-1 in the lung tissues of burn-induced ALI rats. These results suggested that hUCMSCs-exo exhibited a protective role against burn-induced ALI by inhibiting ferroptosis, partly owing to the activation of Nrf2/HO-1 pathway, thus providing a novel therapeutic strategy for burn-induced ALI.
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Developing the topochemical polymerization of metal-organic frameworks (MOFs) is of pronounced significance for expanding their functionalities but is still a challenge on third-order nonlinear optics (NLO). Here, we report diacetylene MOF (CAS-1-3) films prepared using a stepwise deposition method and film structural transformation approach, featuring dynamic structural diversity. The MOF structures were determined by the three-dimensional electron diffraction (3D ED) method from nanocrystals collected from the films, which provides a reliable strategy for determining the precise structure of unknown MOF films. We demonstrate the well-aligned diacetylene groups in the MOFs can promote topological polymerization to produce a highly conjugated system under thermal stimulation. As a result, the three MOF films have distinct NLO properties: the CAS-1 film exhibits saturable absorption (SA) while CAS-2 and CAS-3 films exhibit reverse saturable absorption (RSA). Interestingly, due to the topochemical polymerization of the MOF films, a transition from SA to RSA response was observed with increasing temperatures, and the optical limiting effect was significantly enhanced (â¼46 times). This study provides a new strategy for preparing NLO materials and thermally regulation of nonlinear optics.
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After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situ using quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150Glued and Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell's endocytic transport mechanism.
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2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.
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Antineoplásicos , Cromonas , Ácidos de Lewis , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Humanos , Cromonas/química , Cromonas/farmacología , Cromonas/síntesis química , Línea Celular Tumoral , Ácidos de Lewis/química , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Catálisis , Relación Estructura-ActividadRESUMEN
Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.
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Endocitosis , Virus de la Influenza A , Microtúbulos , Puntos Cuánticos , Puntos Cuánticos/química , Microtúbulos/metabolismo , Microtúbulos/virología , Humanos , Virus de la Influenza A/fisiología , Internalización del Virus , Animales , Perros , Células de Riñón Canino Madin Darby , Citoesqueleto de Actina/metabolismoRESUMEN
The mechanical properties of halide perovskites have been attracting ever-increasing interest for their significant importance in future industrial applications. However, studies focused on the effect of B-site substitution of molecular perovskites on their mechanical properties are rare, which makes it favorable to shed light on their fundamental structure-mechanical property relationships. Here, using isostructural halide perovskites, [C4H12N2][BCl3]·H2O (B = NH4+; K+), constructed by ionic bonds and hydrogen bonds, respectively, as the model systems, we investigate their mechanical properties through high-pressure synchrotron X-ray diffraction experiments and density functional theory calculations. Owing to the similar sizes of NH4+ and K+, the two compounds possess almost identical cell parameters and frameworks. Upon compression, the two perovskites exhibit analogous behavior except for slight differences in the shrinkage ratio of principal axes and the onset pressure of amorphization. The fitted bulk moduli of [C4H12N2][KCl3]·H2O and [C4H12N2][NH4Cl3]·H2O are 43.89 and 27.28 GPa, respectively. These results demonstrate that the simple replacement of K+ by NH4+ can significantly reduce the structural rigidity of the corresponding compounds, which is ascribed to the weaker strength of NH4â¯Cl hydrogen bonds than that of K-Cl bonds.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). METHODS: Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. RESULTS: Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. CONCLUSIONS: This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD's adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.
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Diabetes Mellitus Tipo 2 , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Anciano , Factores de Riesgo , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Volumen Sistólico , Adulto , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/etiología , Fenómenos BiomecánicosRESUMEN
BACKGROUND: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). METHODS: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. RESULTS: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (ß = - 6.05, P < 0.001) and impaired global longitudinal strain (ß = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (ß = - 45.81, P = 0.008), LV global circumferential strain (ß = 18.25, P = 0.003), LA reservoir strain (ß = - 59.20, P < 0.001) and strain rate (ß = - 2.90, P = 0.002). CONCLUSIONS: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.