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JOURNAL/nrgr/04.03/01300535-202506000-00030/figure1/v/2024-08-05T133530Z/r/image-tiff Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors--NeuroD1, Ascl1, and Dlx2--in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore, we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4 (astrocyte endfeet signal), CX43 (gap junction signal), and S100ß. Importantly, none of these changes could be attributed to transgene leakage into pre-existing neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.
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Claudin18.2 (CLDN18.2) has emerged as a significant target in the treatment of advanced gastric cancer. The screening of patients positive for CLDN18.2 is crucial for the effective application of targeted therapies specific to CLND18.2. In this study, we developed a novel nanobody-based probe, [99mTc]Tc-PHG102, for use in nuclear medicine. We analyzed its radiochemical yield and stability to ensure accurate probe characterization. Additionally, we assessed the probe's affinity and specificity toward the CLDN18.2 target and evaluated its efficacy in the BGC82318.2 xenograft model for SPECT/CT imaging of gastric cancer. The binding of [99mTc]Tc-PHG102 to HEK-293T18.2 and BGC82318.2 cells was notably higher than its binding to HEK-293T18.1, HEK-293T, and BGC823 cells, with bound values of 12.87 ± 1.46%, 6.16 ± 0.34%, 1.25 ± 0.22%, 1.14 ± 0.26%, and 1.32 ± 0.07% AD, respectively. The binding ability of [99mTc]Tc-PHG102 was significantly different between CLDN18.2-positive and negative cells (P < 0.001). Imaging results demonstrated a time-dependent tumor accumulation of the radiotracer. Notably, at 0.5 h postinjection, rapid accumulation was observed with an average tumor uptake of 4.63 ± 0.81% ID/cc (n = 3), resulting in clear tumor visualization. By 1 h postinjection, as [99mTc]Tc-PHG102 was rapidly metabolized, a decrease in uptake by other organs was noted. Preliminary clinical imaging trials further confirmed the safety and effectiveness of the probe, indicating specificity for lesions expressing CLDN18.2 in gastric cancer and favorable in vivo metabolic properties. In conclusion, the nanobody-based probe [99mTc]Tc-PHG102 proves to be a safe and effective tool for detecting CLDN18.2 expression levels in gastric cancer tumors and for screening CLDN18.2-positive patients.
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BACKGROUND: Acute respiratory distress syndrome (ARDS) after cardiac surgery is a severe respiratory complication with high mortality and morbidity. Traditional clinical approaches may lead to under recognition of this heterogeneous syndrome, potentially resulting in diagnosis delay. This study aims to develop and external validate seven machine learning (ML) models, trained on electronic health records data, for predicting ARDS after cardiac surgery. METHODS: This multicenter, observational cohort study included patients who underwent cardiac surgery in the training and testing cohorts (data from Nanjing First Hospital), as well as those patients who had cardiac surgery in a validation cohort (data from Shanghai General Hospital). The number of important features was determined using the sliding windows sequential forward feature selection method (SWSFS). We developed a set of tree-based ML models, including Decision Tree, GBDT, AdaBoost, XGBoost, LightGBM, Random Forest, and Deep Forest. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score. The SHapley Additive exPlanation (SHAP) techinque was employed to interpret the ML model. Furthermore, a comparison was made between the ML models and traditional scoring systems. ARDS is defined according to the Berlin definition. RESULTS: A total of 1996 patients who had cardiac surgery were included in the study. The top five important features identified by the SWSFS were chronic obstructive pulmonary disease, preoperative albumin, central venous pressure_T4, cardiopulmonary bypass time, and left ventricular ejection fraction. Among the seven ML models, Deep Forest demonstrated the best performance, with an AUC of 0.882 and a Brier score of 0.809 in the validation cohort. Notably, the SHAP values effectively illustrated the contribution of the 13 features attributed to the model output and the individual feature's effect on model prediction. In addition, the ensemble ML models demonstrated better performance than the other six traditional scoring systems. CONCLUSIONS: Our study identified 13 important features and provided multiple ML models to enhance the risk stratification for ARDS after cardiac surgery. Using these predictors and ML models might provide a basis for early diagnostic and preventive strategies in the perioperative management of ARDS patients.
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Procedimientos Quirúrgicos Cardíacos , Aprendizaje Automático , Síndrome de Dificultad Respiratoria , Humanos , Síndrome de Dificultad Respiratoria/etiología , Masculino , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Anciano , Curva ROC , Área Bajo la CurvaRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is one of the most deadly cancers in the world. It usually has a bad prognosis and is challenging to identify in its early stages. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be important in the control of signaling pathways, cell behaviors, and epigenetic modification that contribute to the growth of tumors. The purpose of this work was to examine the relationship between CCA and lncRNA AL161431.1. METHODS: Using TCGA clinical survival data, we evaluated the association between AL161431.1 expression and patient prognosis. Using the program cluster Profiler R, enrichment analysis was performed. Additionally, the association between immune cell infiltration and AL161431.1 expression was evaluated by a review of the TCGA database. Next, to ascertain if AL161431.1 influences tumor growth, migration, and invasion in CCA, functional in vitro assays were conducted. Quantitative real-time polymerase chain reaction (qPCR) was employed to gauge AL161431.1 expression levels in CCA cells. Western blot was used to measure protein levels. RESULTS: In CCA, AL161431.1 was extremely expressed. The patients in the high-risk group had a significantly poorer overall survival (OS) than the patients in the low-risk group. A more thorough look at the TCGA data showed a relationship between high expression levels of AL161431.1 and increased infiltration of T cells, T helper cells, and NK CD56dim cells. Furthermore, AL161431.1 knockdown in CCA cells impeded invasion, migration, and proliferation and also lowered the expression of phosphorylated Smad2/Smad3 to restrain the TGFß/SMAD signaling pathway. CONCLUSIONS: Our results indicate that the lncRNA AL161431.1 activates the TGFß/SMAD signaling pathway to enhance CCA development and metastasis. AL161431.1 could be a novel target for cholangiocarcinoma treatment or a diagnostic marker.
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Neoplasias de los Conductos Biliares , Movimiento Celular , Colangiocarcinoma , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Colangiocarcinoma/metabolismo , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Técnicas de Silenciamiento del Gen , Pronóstico , Femenino , Masculino , Invasividad NeoplásicaRESUMEN
INTRODUCTION: Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC). METHODS: Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC. RESULTS: NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation. CONCLUSION: Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.
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Apoptosis , Proliferación Celular , Resistencia a Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Largo no Codificante , Transducción de Señal , Humanos , ARN Largo no Codificante/genética , Resistencia a Antineoplásicos/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
The appropriate degradation characteristics of polydioxanone (PDO) are necessary for the safety and effectiveness of stents. This study aimed to investigate the degradation of PDO weaving tracheal stents (PW stents)in vitroandin vivo. The degradation solution ofS. aureus(SAU),E. coli(ECO),P. aeruginosa(PAE), and control (N) were prepared, and the PW stents were immersed for 12 weeks. Then, the radial support force, weight retention, pH, molecular structure, thermal performance, and morphology were determined. Furthermore, the PW stents were implanted into the abdominal cavity of rabbits, and omentum was embedded. At feeding for 16 weeks, the mechanical properties, and morphology were measured. During the first 8 weeks, the radial support force in all groups was progressively decreased. At week 2, the decline rate of radial support force in the experimental groups was significantly faster compared to the N group, and the difference was narrowed thereafter. The infrared spectrum showed that during the whole degradation process, SAU, ECO and PAE solution did not lead to the formation of new functional groups in PW stents.In vitroscanning electron microscope observation showed that SAU and ECO were more likely to gather and multiply at the weaving points of the PW stents, forming colonies.In vivoexperiments showed that the degradation in the concavity of weaving points of PW stents was more rapid and severe. The radial support loss rate reached more than 70% at week 4, and the radial support force was no longer measurable after week 8. In omentum, multinuclear giant cells and foreign giant cells were found to infiltrate. PW stents have good biocompatibility. The degradation rate of PW stents in the aseptic conditionsin vivowas faster than in the bacteriological environmentin vitro.
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Ensayo de Materiales , Polidioxanona , Stents , Tráquea , Animales , Polidioxanona/química , Conejos , Materiales Biocompatibles/química , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Concentración de Iones de Hidrógeno , EpiplónRESUMEN
PoissonERM is an R package used to conduct exposure-response (ER) analysis on binary outcomes for establishing the relationship between exposure and the occurrence of adverse events (AE). While Poisson regression could be implemented with glm(), PoissonERM provides a simple way to semi-automate the entire analysis and generate an abbreviated report as an R markdown (Rmd) file that includes the essential analysis details with brief conclusions. PoissonERM processes the provided data set using the information from the user's control script and generates summary tables/figures for the exposure metrics, covariates, and event counts of each endpoint (each type of AE). After checking the incidence rate of each AE, the correlation, and missing values in each covariate, an exposure-response model is developed for each endpoint based on the provided specifications. PoissonERM has the flexibility to incorporate and compare multiple scale transformations in its modeling. The best exposure metric is selected based on a univariate model's p-value or deviance ( Δ D $$ \Delta D $$ ) as specified. If a covariate search is specified in the control script, the final model is developed using backward elimination. PoissonERM identifies and avoids highly correlated covariates in the final model development of each endpoint. Predicting event incidence rates using external (simulated) exposure metric data is an additional functionality in PoissonERM, which is useful to understand the event occurrence associated with certain dose regimens. The summary outputs of the cleaned data, model developments, and predictions are saved in the working folder and can be compiled into a HTML report using Rmd.
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Due to rapid technological advancements, remote patient monitoring (RPM) technology has gained traction in recent years. While the effects of specific RPM interventions are known, few published reviews examine RPM in the context of care transitions from an inpatient hospital setting to a home environment. In this systematic review, we addressed this gap by examining the impacts of RPM interventions on patient safety, adherence, clinical and quality of life outcomes and cost-related outcomes during care transition from inpatient care to a home setting. We searched five academic databases (PubMed, CINAHL, PsycINFO, Embase and SCOPUS), screened 2606 articles, and included 29 studies from 16 countries. These studies examined seven types of RPM interventions (communication tools, computer-based systems, smartphone applications, web portals, augmented clinical devices with monitoring capabilities, wearables and standard clinical tools for intermittent monitoring). RPM interventions demonstrated positive outcomes in patient safety and adherence. RPM interventions also improved patients' mobility and functional statuses, but the impact on other clinical and quality-of-life measures, such as physical and mental health symptoms, remains inconclusive. In terms of cost-related outcomes, there was a clear downward trend in the risks of hospital admission/readmission, length of stay, number of outpatient visits and non-hospitalisation costs. Future research should explore whether incorporating intervention components with a strong human element alongside the deployment of technology enhances the effectiveness of RPM. The review highlights the need for more economic evaluations and implementation studies that shed light on the facilitators and barriers to adopting RPM interventions in different care settings.
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Cardiac fibrosis following myocardial infarction (MI) seriously affects the prognosis and survival rate of patients. This study aimed to determine the effect and regulation mechanism of the dedicator of cytokinesis 2 (DOCK2) during this process. Experiments were carried out in mice in vivo, and in Ang II treated cardiac fibroblasts (CFs) in vitro. DOCK2 was increased in mouse myocardial tissues after MI and Ang II-treated CFs. In MI mice, DOCK2 silencing improved cardiac function, and ameliorated cardiac fibrosis. DOCK2 knockdown suppressed the activation of CFs and decreased the expression of α-SMA, collagen I, and collagen III. Suppression of DOCK2 mitigated Ang II induced migration of CFs. DOCK2 inhibition reduced the activity of the PI3K/Akt and Wnt/ß-catenin pathways, while this change could be reversed by the pathway activators, SC79 and SKL2001. In summary, DOCK2 suppression improves cardiac dysfunction and attenuates cardiac fibrosis after MI via attenuating PI3K/Akt and Wnt/ß-catenin pathways.
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Background/purpose: The impact of temporomandibular joint (TMJ) osseous destruction on bone mineral density (BMD) remains unclear due to controversial findings. Besides, no previous study has explored the relationship between idiopathic condylar resorption (ICR) and body composition. This study aimed to investigate the relationship between ICR and BMD or body composition. Materials and methods: Between July 2018 and August 2022, patients evaluated by an experienced dentist and diagnosed with temporomandibular disorders (TMDs) were referred to our center. They were recruited while they received the magnetic resonance image (MRI) examination, BMD and body composition completely. Patients were further categorized into TMDs with or without ICR groups according to MRI findings. One-way analysis of variance was used to compare the variables of BMD and body composition in the two groups. Results: In total, 67 patients were included in the analysis, with 42 categorized as TMDs with ICR and 25 as TMDs without ICR. Patients with ICR had a significantly higher lean mass percentage and lower fat mass percentage; lower android/gynoid fat ratio, and visceral adipose tissue area than those without ICR (P < 0.05). Besides, patients above age 30 with ICR had lower Z scores (P = 0.017) compared with subjects without ICR. Conclusion: TMDs patients with ICR show a relationship with body composition and affect the lean and fat mass distribution, especially android/gynoid fat ratio. The pathophysiological mechanism remains unclear. Further researches to investigate teeth binding, malocclusion and dietary habits are important to understand the association of ICR, BMD and body composition.
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Bosonic quantum devices offer a novel approach to realize quantum computations, where the quantum two-level system (qubit) is replaced with the quantum (an)harmonic oscillator (qumode) as the fundamental building block of the quantum simulator. The simulation of chemical structure and dynamics can then be achieved by representing or mapping the system Hamiltonians in terms of bosonic operators. In this Perspective, we review recent progress and future potential of using bosonic quantum devices for addressing a wide range of challenging chemical problems, including the calculation of molecular vibronic spectra, the simulation of gas-phase and solution-phase adiabatic and nonadiabatic chemical dynamics, the efficient solution of molecular graph theory problems, and the calculations of electronic structure.
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Aftobetin is a non-invasive diagnosis probe of Alzheimer's disease, that can bind with aggregated ß-amyloid peptide in eye's lenses, used for early diagnosis of Alzheimer's disease in a rapid and painless mode. The reported synthesis of this probe fell short in the aspects of greenness and economy due to the involvement of toxic Chromium(IV) oxidant, noble palladium catalyst, elevated reaction temperature, the long reaction time as well as the cumbersome workup. Herein, a holistic optimization of the synthetic process was achieved via the employment of flow technology and heterogenous photocatalysis. Firstly, the integration of heterogenous carbon nitrides photocatalysis and circulation flow technology furnished the air oxidation of alcohol and nickel catalyzed C-N coupling at 20-g scale, thus avoiding the use of toxic Chromium and precious palladium species respectively. Flow-intensified esterification between acyl chloride and alcohol, just taking 30 seconds replaced the Steglich esterification of 6 hours, also avoiding the generation of difficult-to-remove dicyclohexylurea. Finally, C-N coupling, esterification and Knoevenagel condensation were telescoped together, thus simplifying the reaction workup. This fully-flow protocol led to the on-demand synthesis of eight probes.
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Osteoporosis development is linked to abnormal bone marrow mesenchymal stem cells (BMSCs) differentiation. N6-methyladenosine (m6A), a prevalent mRNA modification, is known to influence BMSCs' osteogenic capacity. Qianggu decoction (QGD), a traditional Chinese medicine for osteoporosis, has unknown effects on BMSCs differentiation. This study investigates QGD's impact on BMSCs and its potential to ameliorate osteoporosis through m6A regulation. Using Sprague-Dawley (SD) rats with ovariectomy-induced osteoporosis, it is evaluated QGD's antiosteoporotic effects through micro-CT, histology, Western blotting, and osteoblastogenesis markers. QGD is found to enhance bone tissue growth and upregulate osteogenic markers Runx2, OPN, and OCN. It also promoted BMSCs osteogenic differentiation, as shown by increased calcium nodules and ALP activity. QGD treatment significantly increased m6A RNA levels and Mettl3 expression in BMSCs. Silencing Mettl3 with siRNA negated QGD's osteogenic effects. Collectively, QGD may improve BMSCs differentiation and mitigate osteoporosis, potentially through Mettl3-mediated m6A modification.
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In this work, we have implemented the time-dependent density functional theory approximate auxiliary s function (TDDFT-aas) method, which is an approximate TDDFT method. Instead of calculating the exact two-center electron integrals in the K coupling matrix when solving the Casida equation, we approximate the integrals, thereby reducing the computational cost. In contrast to the related TDDFT plus tight-binding (TDDFT+TB) method, a new type of gamma function is used in the coupling matrix that does not depend on the tight-binding parameters. The calculated absorption spectra of silver and gold nanoparticles using TDDFT-aas show good agreement with TDDFT and TDDFT+TB results. In addition, we have implemented the analytical excited-state gradients for the TDDFT-aas method, which makes it possible to calculate the emission energy of molecular systems.
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Despite the discovery of a series of fullerenes and a handful of noncarbon clusters with the typical topology of I h-C60, the smallest fullerene with a large degree of curvature, C20, and its other-element counterparts are difficult to isolate experimentally. In coinage metal nanoclusters (NCs), the first all-gold fullerene, Au32, was discovered after a long-lasting pursuit, but the isolation of similar silvery fullerene structures is still challenging. Herein, we report a flying saucer-shaped 102-nuclei silver NC (Ag102) with a silvery fullerene kernel of Ag32, which is embraced by a robust cyclic anionic passivation layer of (KPO4)10. This Ag32 kernel can be viewed as a non-centered icosahedron Ag12 encaged into a dodecahedron Ag20, forming the silvery fullerene of Ag12@Ag20. The anionic layer (KPO4)10 is located at the interlayer between the Ag32 kernel and Ag70 shell, passivating the Ag32 silvery fullerene and templating the Ag70 shell. The t BuPhS- and CF3COO- ligands on the silver shell show a regioselective arrangement with the 60 t BuPhS- ligands as expanders covering the upper and lower of the flying saucer and 10 CF3COO- as terminators neatly encircling the edges of the structure. In addition, Ag102 shows excellent photothermal conversion efficiency (η) from the visible to near-infrared region (η = 67.1% ± 0.9% at 450 nm, 60.9% ± 0.9% at 660 nm and 50.2% ± 0.5% at 808 nm), rendering it a promising material for photothermal converters and potential application in remote laser ignition. This work not only captures silver kernels with the topology of the smallest fullerene C20, but also provides a pathway for incorporating alkali metal (M) into coinage metal NCs via M-oxoanions.
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Background: To quantify the changes in dynamic visual acuity (DVA) and explain the hidden reasons after acute exposure to hypobaric hypoxia status. Methods: The study group comprised 18 healthy male and 15 healthy female participants aged 20-24 years old. DVA was measured with the self-developed software of Meidixin (Tianjin) Co., Ltd. Measurements were taken at eight altitudes. Data analysis was performed using the Kolmogorov-Smirnov test, paired sample T-test, and two-way repeated measures analysis of variance (ANOVA) for repeated measurements. Results: At constant altitude, DVA showed an overall decreasing trend with increasing angular velocity and a fluctuating decrease at the vast majority of altitudes. At constant angular velocities, DVA gradually increased with altitude, with the most pronounced increase in DVA at altitude 5, and thereafter a gradual decrease in DVA as altitude increased. Finally, as altitude decreased, DVA increased again and reached a higher level at the end of the experiment, which was superior to the DVA in the initial state. Conclusion: Under a hypobaric hypoxic environment at high altitude, DVA was affected by the angular velocity and the degree of hypoxia, manifesting as an increase or decrease in DVA, which affects the pilot's observation of the display and control interfaces during the driving process, acquisition of information, and decision-making ability, which in turn may potentially jeopardize the safety of the flight.
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The significant effects of lipid binding on the functionality of potassium channel KcsA have been validated by brilliant studies. However, the specific interactions between lipids and KcsA, such as binding parameters for each binding event, have not been fully elucidated. In this study, we employed native mass spectrometry to investigate the binding of lipids to KcsA and their effects on the channel. The tetrameric structure of KcsA remains intact even in the absence of lipid binding. However, the subunit architecture of the E71A mutant, which is constantly open at low pH, relies on tightly associated copurified lipids. Furthermore, we observed that lipids exhibit weak binding to KcsA at high pH when the channel is at a closed/inactivation state in the absence of permeant cation K+. This feeble interaction potentially facilitates the association of K+ ions, leading to the transition of the channel to a resting closed/open state. Interestingly, both anionic and zwitterionic lipids strongly bind to KcsA at low pH when the channel is in an open/inactivation state. We also investigated the binding patterns of KcsA with natural lipids derived from E. coli and Streptomyces lividans. Interestingly, lipids from E. coli exhibited much stronger binding affinity compared to the lipids from S. lividans. Among the natural lipids from S. lividans, free fatty acids and triacylglycerols demonstrated the tightest binding to KcsA, whereas no detectable binding events were observed with natural phosphatidic acid lipids. These findings suggest that the lipid association pattern in S. lividans, the natural host for KcsA, warrants further investigation. In conclusion, our study sheds light on the role of lipids in stabilizing KcsA and highlights the importance of specific lipid-protein interactions in modulating its conformational states.
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Hydrogen-bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co2-HOF-X, X=COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12â M HCl) and strong base (5â M NaOH) for at least 10â days. More impressively, by varying the -X groups of the dinuclear cobalt complexes, the microenvironment of Co2-HOF-X can be modulated, giving rise to obviously different photocatalytic H2 production rates, following the -X group sequence of -COOMe>-Br>-tBu>-OMe. The optimized Co2-HOF-COOMe shows H2 generation rate up to 12.8â mmol g-1 h-1 in the absence of any additional noble-metal photosensitizers and cocatalysts, which is superior to most reported Pt-assisted photocatalytic systems. Experiments and theoretical calculations reveal that the -X groups grafted on Co2-HOF-X possess different electron-withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H2 production, and leading to the distinctly different photocatalytic activity.
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OBJECTIVE: To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation. METHODS: The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods. Among them, 20 patients were fixed with single small incision with honeycomb titanium plate (titanium plate group), including 11 males and 9 females, aged from 23 to 65 years old with an average of (47.40±12.58) years old;12 patients on the left side, 8 patients on the right side;11 patients with type â ¢, 3 patients with type â £, and 6 patients with type â ¤ according to Rockwood classification. Twenty patients were fixed with clavicular hook plate (clavicular hook group), including 8 males and 12 females, aged from 24 to 65 years old with an average of (48.40±12.08) years old;12 patients on the left side, 8 patients on the right side;10 patients with type â ¢, 2 patients with type â £, and 8 patients with type â ¤ according to Rockwood classification. Operative time, incision length, intraoperative blood loss, hospital stay, visual analogue scale (VAS) and Constant-Murley score of shoulder joint function were compared between two groups. Anteroposterior radiographs of the affected shoulder joint were recorded before, immediately and 6 months after surgery, and the coracoclavicular distance was measured and compared. RESULTS: Both groups of patients were successfully completed operation without serious complications. All patients were followed up for 6 to 15 months with an average of (11.9±4.8) months. There were no incisional infection, internal plant fracture or failure, bone tunnel fracture and other complications occurred. The incision length of titanium plate group (35.90±3.14) mm was significantly shorter than that of clavicular hook group (49.30±3.79) mm (P<0.05). There were no significant difference in operative time, intraoperative blood loss and hospital stay between two groups (P>0.05). At 1 and 3 months after operation, VAS of titanium plate group was lower than that of clavicular hook group (P<0.05). Connstant-Murley scores in titanium plate group at 1, 3 and 6 months after operation were (86.80±1.36), (91.60±2.32) and (94.90±2.22), respectively;and in clavicular hook group were (78.45±5.47), (85.55±2.01) and (90.25±1.92), which were higher than that of clavicular hook group (P<0.05). There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after operation(P>0.05). CONCLUSION: For the treatment of acute acromioclavicular joint dislocation, single small incision combined with honeycomb titanium plate have advantages of shorter incision, fast recovery of shoulder joint function without the second operation, and has good satisfaction of patient.
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Articulación Acromioclavicular , Placas Óseas , Titanio , Humanos , Masculino , Articulación Acromioclavicular/cirugía , Articulación Acromioclavicular/lesiones , Femenino , Persona de Mediana Edad , Adulto , Anciano , Estudios Retrospectivos , Luxaciones Articulares/cirugía , Adulto Joven , Fijación Interna de Fracturas/métodosRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC), which is so called because of the lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) receptors on the cancer cells, accounts for 10%-15% of all breast cancers. The heterogeneity of the tumor microenvironment is high. However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood. METHODS: We analyzed single-cell RNA sequencing data from five HER2 positive, 12 ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry. RESULTS: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2-integrin-aLb2 complex, and then release interleukin 1 beta (IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth. CONCLUSION: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.