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1.
Prehosp Disaster Med ; : 1-9, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712485

RESUMEN

INTRODUCTION: Medical resuscitations in rugged prehospital settings require emergency personnel to perform high-risk procedures in low-resource conditions. Just-in-Time Guidance (JITG) utilizing augmented reality (AR) guidance may be a solution. There is little literature on the utility of AR-mediated JITG tools for facilitating the performance of emergent field care. STUDY OBJECTIVE: The objective of this study was to investigate the feasibility and efficacy of a novel AR-mediated JITG tool for emergency field procedures. METHODS: Emergency medical technician-basic (EMT-B) and paramedic cohorts were randomized to either video training (control) or JITG-AR guidance (intervention) groups for performing bag-valve-mask (BVM) ventilation, intraosseous (IO) line placement, and needle-decompression (Needle-d) in a medium-fidelity simulation environment. For the interventional condition, subjects used an AR technology platform to perform the tasks. The primary outcome was participant task performance; the secondary outcomes were participant-reported acceptability. Participant task score, task time, and acceptability ratings were reported descriptively and compared between the control and intervention groups using chi-square analysis for binary variables and unpaired t-testing for continuous variables. RESULTS: Sixty participants were enrolled (mean age 34.8 years; 72% male). In the EMT-B cohort, there was no difference in average task performance score between the control and JITG groups for the BVM and IO tasks; however, the control group had higher performance scores for the Needle-d task (mean score difference 22%; P = .01). In the paramedic cohort, there was no difference in performance scores between the control and JITG group for the BVM and Needle-d tasks, but the control group had higher task scores for the IO task (mean score difference 23%; P = .01). For all task and participant types, the control group performed tasks more quickly than in the JITG group. There was no difference in participant usability or usefulness ratings between the JITG or control conditions for any of the tasks, although paramedics reported they were less likely to use the JITG equipment again (mean difference 1.96 rating points; P = .02). CONCLUSIONS: This study demonstrated preliminary evidence that AR-mediated guidance for emergency medical procedures is feasible and acceptable. These observations, coupled with AR's promise for real-time interaction and on-going technological advancements, suggest the potential for this modality in training and practice that justifies future investigation.

2.
Atherosclerosis ; 392: 117527, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38583286

RESUMEN

BACKGROUND AND AIMS: Diabetic atherosclerotic vascular disease is characterized by extensive vascular calcification. However, an elevated blood glucose level alone does not explain this pathogenesis. We investigated the metabolic markers underlying diabetic atherosclerosis and whether extracellular Hsp90α (eHsp90α) triggers vascular endothelial calcification in this particular metabolic environment. METHODS: A parallel human/animal model metabolomics approach was used. We analyzed 40 serum samples collected from 24 patients with atherosclerosis and from the STZ-induced ApoE-/- mouse model. A multivariate statistical analysis of the data was performed, and mouse aortic tissue was collected for the assessment of plaque formation. In vitro, the effects of eHsp90α on endothelial cell calcification were assessed by serum analysis, Western blotting and immunoelectron microscopy. RESULTS: Diabetic ApoE-/- mice showed more severe plaque lesions and calcification damage. Stearamide, oleamide, l-thyroxine, l-homocitrulline and l-citrulline are biomarkers of diabetic ASVD; l-thyroxine was downregulated in both groups, and the thyroid sensitivity index was correlated with serum Hsp90α concentration. In vitro studies showed that eHsp90α increased Runx2 expression in endothelial cells through the LRP1 receptor. l-thyroxine reduced the increase in Runx2 levels caused by eHsp90α and affected the distribution and expression of LRP1 through hydrogen bonding with glutamine at position 1054 in the extracellular segment of LRP1. CONCLUSIONS: This study provides a mechanistic link between characteristic serum metabolites and diabetic atherosclerosis and thus offers new insight into the role of extracellular Hsp90α in promoting vascular calcification.

3.
PLoS Genet ; 20(4): e1011235, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38648200

RESUMEN

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.


Asunto(s)
Neoplasias , Osteopontina , Macrófagos Asociados a Tumores , Humanos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Pronóstico , Neoplasias/inmunología , Neoplasias/genética , Osteopontina/genética , Osteopontina/metabolismo , Regulación Neoplásica de la Expresión Génica , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , beta Catenina/genética , beta Catenina/metabolismo , Análisis de la Célula Individual , Transducción de Señal , Macrófagos/inmunología , Macrófagos/metabolismo , Comunicación Celular/inmunología
4.
Transfus Clin Biol ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38670448

RESUMEN

BACKGROUND: An adequate blood supply is an important guarantee for saving lives and protecting health. In order to manage the blood supply more effectively when the condition of demand and supply are uncertainty, it is very important to forecast the demands of blood resources. MATERIALS AND METHODS: SARIMAX model and LSTM model were integrated into the prediction system of blood station. The collection and supply data of blood components was directly imported into the forecasting models to achieve automatic data update and model update. The forecasting daily demands of apheresis platelets, washing red blood cells (RBCs), suspended RBCs and plasma were recorded from January to June 2023 and compared with real data. RESULTS: The prediction models had good forecasting performances. In the goodness of fit results of apheresis platelet model, the maximum value of coefficient of determination (R2) could reach 87.6%, and the minimum value of the mean absolute percentage error (MAPE) was only 0.0037. The predicted data of washing RBCs could be basically fitted, and the MAPE was 0.0121. For the prediction of suspended RBCs, the R2 was greater than 66%, and the MAPE could be 0.0372. The plasma model generated very high goodness of fit results, with R2 of over 90% and the lowest MAPE of 0.0394. CONCLUSION: The forecasting models, which predicts future demands of different blood components based on historical data, can help managers to overcome the challenges of blood stock control more effectively, thereby reducing blood waste and blood shortages.

5.
Asian J Pharm Sci ; 19(1): 100888, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38434719

RESUMEN

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

6.
Ophthalmic Surg Lasers Imaging Retina ; 55(4): 212-219, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38319059

RESUMEN

BACKGROUND AND OBJECTIVE: We sought to establish normative quantitative contrast sensitivity function (qCSF) values in healthy adult eyes and investigate the effect of age on qCSF. PATIENTS AND METHODS: Healthy eyes underwent qCSF testing (adaptive sensory technology) and Snellen's visual acuity (VA). Descriptive statistics and mixed-effects multivariable linear regressions were evaluated. RESULTS: A total of 334 eyes (290 patients) with median age 61 years (range 21 to 88) had qCSF values as follows: area under the log contrast sensitivity function curve: 1.18; contrast acuity: 1.32; contrast sensitivity (CS) at 1 cycle per degree (cpd): 1.32; CS at 1.5 cpd: 1.37; CS at 3 cpd: 1.38; CS at 6 cpd: 1.20; CS at 12 cpd: 0.69; CS at 18 cpd: 0.22. Linear reductions in qCSF values per decade of age ranged from -0.02 to -0.07 vs 0.01 for visual acuity (VA). Age had a greater effect on the majority of qCSF values than VA (beta standardized regression coefficient ranged from -0.309 to -0.141 for qCSF values vs 0.177 for VA). CONCLUSIONS: We herein establish a normative database for qCSF and quantify the effect of age on qCSF values, adding evidence towards the validation of qCSF as a clinical endpoint. [Ophthalmic Surg Lasers Imaging Retina 2024;55:212-219.].


Asunto(s)
Envejecimiento , Sensibilidad de Contraste , Agudeza Visual , Humanos , Sensibilidad de Contraste/fisiología , Adulto , Femenino , Masculino , Persona de Mediana Edad , Agudeza Visual/fisiología , Anciano , Adulto Joven , Anciano de 80 o más Años , Envejecimiento/fisiología , Voluntarios Sanos , Valores de Referencia , Bases de Datos Factuales
7.
Inflammation ; 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38411775

RESUMEN

Retinal inflammation is a pivotal characteristic observed in various retinal degenerative disorders, notably age-related macular degeneration (AMD), primarily orchestrated by the activation of microglia. Targeting the inhibition of microglial activation has emerged as a therapeutic focal point. Quercetin (Qu), ubiquitously present in dietary sources and tea, has garnered attention for its anti-neuroinflammatory properties. However, the impact of Qu on retinal inflammation and the associated mechanistic pathways remains incompletely elucidated. In this study, retinal inflammation was induced in adult male C57BL/6 J mice through intraperitoneal administration of LPS. The results revealed that Qu pre-treatment induces a phenotypic shift in microglia from M1 phenotype to M2 phenotype. Furthermore, Qu attenuated retinal inflammation and stabilized the integrity of the blood-retina barrier (BRB). In vitro experiments revealed that Qu impedes microglial activation, proliferation, and migration, primarily via modulation the ERK/STAT3 signaling pathway. Notably, these actions of Qu significantly contributed to the preservation of photoreceptors. Consequently, Qu pre-treatment holds promise as an effective strategy for controlling retinal inflammation and preserving visual function.

9.
Micromachines (Basel) ; 15(1)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38276852

RESUMEN

Traditional ytterbium-doped high-power fiber lasers generally use a unidirectional output structure. To reduce the cost and improve the efficiency of the fiber laser, we propose a bidirectional output fiber laser (BOFL). The BOFL has many advantages over that of the traditional unidirectional output fiber laser (UOFL) and has a wide application in the industrial field. In theory, the model of the BOFL is established, and a comparison of the nonlinear effect in the traditional UOFL and the BOFL is studied. Experimentally, high-power continuous wave (CW) and quasi-continuous wave (QCW) BOFLs are demonstrated. In the continuous laser, we first combine the BOFL with the oscillating amplifying integrated structure, and a near-single-mode bidirectional 2 × 4 kW output with a total power of above 8 kW is demonstrated. Then, with the simple BOFL, a CW bidirectional 2 × 5 kW output with a total power of above 10 kW is demonstrated. By means of pump source modulation, a QCW BOFL is developed, and the output of a near-single mode QCW laser with a peak output of 2 × 4.5 kW with a total peak power of more than 9 kW is realized. Both CW and QCW output BOFL are the highest powers reported at present.

10.
Clin Exp Ophthalmol ; 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38282307

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) are implicated in retinal pathophysiology; however, their expression profiles and functions in photoreceptor apoptosis are largely unknown. We explored circRNA-expression profiles and circUvrag (host gene: Uvrag, ultraviolet radiation resistance associated gene) function in light-induced photoreceptor apoptosis. METHODS: Sprague-Dawley rats and 661 W photoreceptor cells were exposed to blue light to establish light-induced photoreceptor degeneration. Differentially expressed circRNAs were identified using microarrays. Potential functions of dysregulated circRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircUvrag expression and localization were evaluated using quantitative RT-PCR and fluorescence in situ hybridization, respectively. CircUvrag overexpression and knockdown were induced using a plasmid and a small interfering RNA, respectively, and retinal function and structure were assessed using scotopic electroretinography, haematoxylin-eosin staining, and TUNEL staining. Microglial migration was assessed using IBA1 immunostaining. The apoptosis ratio of photoreceptor cells in vitro was detected using flow cytometry. RESULTS: We identified 764 differentially expressed circRNAs, which were potentially related with the development of retinal structures, including neurons, dendrites, and synapses, and might participate in nervous-system pathophysiology. Light exposure enriched circUvrag in the cytoplasm of photoreceptors in the outer nuclear layer (ONL). CircUvrag knockdown decreased photoreceptor apoptosis and microglial migration to the ONL after light exposure, preserving ONL thickness and a-wave amplitude. In vitro, circUvrag knockdown inhibited photoreceptor apoptosis, although circUvrag overexpression slightly promoted photoreceptor apoptosis. CONCLUSIONS: CircUvrag knockdown attenuated light-induced photoreceptor apoptosis, and might be a potential target in retinal degeneration.

11.
Endocr Pract ; 30(2): 122-127, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37952581

RESUMEN

OBJECTIVE: People with diabetes mellitus, particularly those with limited access to longitudinal care, frequently present to the emergency department (ED). Continuous glucose monitoring (CGM) has been shown to improve outcomes in ambulatory settings, so we hypothesized that it would be beneficial if initiated upon ED discharge. METHODS: We randomized adults with diabetes who were seen in the ED for hypo- or hyperglycemia to either 14 days of flash CGM or care coordination alone. All participants were scheduled to follow up in our diabetes specialty clinic. Outcomes included clinic attendance, the 3-month change in hemoglobin A1c, and repeat ED utilization. RESULTS: We recruited 30 participants, including 13 with newly diagnosed diabetes. All but one (97%) had type 2 diabetes. We found no significant difference between the CGM (n = 16) and control (n = 14) groups in terms of clinic attendance (75 vs 64%, P = .61) or repeat ED utilization (31 vs 50%, P = .35), although our power was low. The absolute reduction in A1c was greater in the CGM group (5.2 vs 2.4%, P = .08). Among newly diagnosed participants for whom we had data, 7 out of 7 in the CGM group had a follow-up A1c under 7% compared to 1 out of 3 in the control group (P = .03). Over 90% of patients and providers found the CGM useful. CONCLUSIONS: Our data demonstrate the feasibility of starting CGM in the ED, a valuable setting for engaging difficult-to-reach patients. Our pilot study was limited by its small sample size, however, as recruitment in the ED can be challenging.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglucemia , Adulto , Humanos , Glucemia , Hemoglobina Glucada , Hipoglucemiantes , Hipoglucemia/diagnóstico , Proyectos Piloto , Diabetes Mellitus Tipo 2/terapia , Automonitorización de la Glucosa Sanguínea , Monitoreo Continuo de Glucosa , Alta del Paciente
12.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 813-822, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37955702

RESUMEN

PURPOSE: The purpose of this study is to investigate test-retest reliability and agreement of the quantitative contrast sensitivity function test (qCSF) in the retina clinic. METHODS: A total of 121 right eyes of 121 patients were tested and consecutively re-tested with qCSF in the retina clinic. Outcomes included area under the logarithm of contrast sensitivity function curve (AULCSF), contrast acuity, and contrast sensitivity thresholds at 1-18 cycles per degree (cpd). Test-retest means were compared with paired t-test, variability was compared with the Brown-Forsythe test, and intraclass correlation coefficient (ICC) and Bland Altman plots evaluated reliability and agreement. RESULTS: Mean test-retest differences for all qCSF metrics ranged from 0.02 to 0.05 log units without statistically significant differences in variability. Standard deviations ranged from 0.08 to 0.14. Coefficients of repeatability ranged from 0.16 to 0.27 log units. ICC > 0.9 for all metrics except 1cpd (ICC = 0.84, all p < 0.001); AULCSF ICC = 0.971. CONCLUSION: qCSF-measured contrast sensitivity shows great test-retest repeatability and agreement in the retina clinic.


Asunto(s)
Sensibilidad de Contraste , Pruebas de Visión , Humanos , Reproducibilidad de los Resultados , Retina
13.
Acta Pharm Sin B ; 13(12): 5091-5106, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38045037

RESUMEN

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

14.
Sci Rep ; 13(1): 21218, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040833

RESUMEN

Quasi-continuous wave (QCW) laser has a very broad application in the industrial field, especially in additive manufacturing, surface treatment, laser cutting, laser cleaning, and laser drilling. Compared with the unidirectional fiber laser, the bidirectional output can be achieved two ports high power output with only one resonator, which can greatly reduce the industrial cost. However, there are few researches on QCW fiber lasers with bidirectional output. Here, we optimized and demonstrated a bidirectional output QCW laser with output power of 2 × 4.5 kW based on a double-clad ytterbium-doped fiber with a core/cladding diameter of 25/400 µm. The peak power at both ends reached 4515 W and 4694 W, respectively. The Raman suppression ratio at both ends of A and B is about 12 dB, and the beam quality factor M2 is about 1.37 and 1.42, respectively. The corresponding optical-to-optical efficiency is 79%. To the best of our knowledge, this is the highest peak power of QCW laser with near-single-mode beam quality in a bidirectional structure laser.

15.
Int Wound J ; 21(3): e14476, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37909396

RESUMEN

Diabetic foot ulcer (DFU) complications involve autophagy dysregulation. This study aimed to identify autophagy-related bioindicators in DFU. Differentially expressed genes (DEGs) between DFU and healthy samples were analysed from the Gene Expression Omnibus (GEO) datasets, GSE7014 and GSE29221. The roles of autophagy-related DEGs were investigated using protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO) enrichment, and Gene Set Enrichment Analysis (GSEA). Immune cell infiltration's correlation with these DEGs was also assessed. From the Human Autophagy Database (HADB), 232 autophagy-related genes (ARGs) were identified, with an intersection of 17 key DEGs between GSE7014 and GSE29221. These genes are involved in pathways like autophagy-animal, NOD-like receptor signalling, and apoptosis. In the protein network, epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) showed significant interactions with ARGs. Survival analysis indicated the prognostic importance of calpain 2 (CAPN2), integrin subunit beta 1 (ITGB1), and vesicle-associated membrane protein 3 (VAMP3). Lower immune scores were observed in the type 2 diabetes mellitus (DM2) group than in controls. Autophagy and ARGs significantly influence DFU pathophysiology.

16.
Biomater Sci ; 11(21): 7158-7168, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37718624

RESUMEN

MR-guided focused ultrasound surgery (MRgFUS) is driving a new direction in non-invasive thermal ablation therapy with spatial specificity and real-time temperature monitoring. Although widely used in clinical practice, it remains challenging to completely ablate the tumor margin due to fear of damaging the surrounding tissues, thus leading to low efficacy and a series of complications. Herein, we have developed novel pH-responsive drug-loading magnetosomes (STPSD nanoplatform) for increasing the T2-contrast and improved the ablation efficiency with a clinical MRgFUS system. Specifically, this STPSD nanoplatform is functionalized by pH-responsive peptides (STP-TPE), encapsulating superparamagnetic iron oxide (SPIO) and doxorubicin (DOX), which can cause drug release and SPIO deposition at the tumor site triggered by acidity and MRgFUS. Under MRgFUS treatment, the increased vascular permeability caused by hyperthermia can improve the uptake of SPIO and DOX by tumor cells, so as to enhance ultrasound energy absorption and further enhance the efficacy of chemotherapy to completely ablate tumor margins. Moreover, we demonstrated that a series of MR sequences including T2-weighted imaging (T2WI), contrast-enhanced T1WI imaging (T1WI C+), maximum intensity projection (MIP), volume rendering (VR) and ADC mapping can be further utilized to monitor the MRgFUS ablation effect in rat models. Overall, this smart nanoplatform has the capacity to be a powerful tool to promote the therapeutic MRgFUS effect and minimize the side effects to surrounding tissues.

17.
J Cell Mol Med ; 27(20): 3026-3052, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37700485

RESUMEN

Prenatal tobacco exposure (PTE) correlates significantly with a surge in adverse pregnancy outcomes, yet its pathological mechanisms remain partially unexplored. This study aims to meticulously examine the repercussions of PTE on placental immune landscapes, employing a coordinated research methodology encompassing bioinformatics, machine learning and animal studies. Concurrently, it aims to screen biomarkers and potential compounds that could sensitively indicate and mitigate placental immune disorders. In the course of this research, two gene expression omnibus (GEO) microarrays, namely GSE27272 and GSE7434, were included. Gene set enrichment analysis (GSEA) and immune enrichment investigations on differentially expressed genes (DEGs) indicated that PTE might perturb numerous innate or adaptive immune-related biological processes. A cohort of 52 immune-associated DEGs was acquired by cross-referencing the DEGs with gene sets derived from the ImmPort database. A protein-protein interaction (PPI) network was subsequently established, from which 10 hub genes were extracted using the maximal clique centrality (MCC) algorithm (JUN, NPY, SST, FLT4, FGF13, HBEGF, NR0B2, AREG, NR1I2, SEMA5B). Moreover, we substantiated the elevated affinity of tobacco reproductive toxicants, specifically nicotine and nitrosamine, with hub genes through molecular docking (JUN, FGF13 and NR1I2). This suggested that these genes could potentially serve as crucial loci for tobacco's influence on the placental immune microenvironment. To further elucidate the immune microenvironment landscape, consistent clustering analysis was conducted, yielding three subtypes, where the abundance of follicular helper T cells (p < 0.05) in subtype A, M2 macrophages (p < 0.01), neutrophils (p < 0.05) in subtype B and CD8+ T cells (p < 0.05), resting NK cells (p < 0.05), M2 macrophages (p < 0.05) in subtype C were significantly different from the control group. Additionally, three pivotal modules, designated as red, blue and green, were identified, each bearing a close association with differentially infiltrated immunocytes, as discerned by the weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis was subsequently conducted on these modules. To further probe into the mechanisms by which immune-associated DEGs are implicated in intercellular communication, 20 genes serving as ligands or receptors and connected to differentially infiltrating immunocytes were isolated. Employing a variety of machine learning techniques, including one-way logistic regression, LASSO regression, random forest and artificial neural networks, we screened 11 signature genes from the intersection of immune-associated DEGs and secretory protein-encoding genes derived from the Human Protein Atlas. Notably, CCL18 and IFNA4 emerged as prospective peripheral blood markers capable of identifying PTE-induced immune disorders. These markers demonstrated impressive predictive power, as indicated by the area under the curve (AUC) of 0.713 (0.548-0.857) and 0.780 (0.618-0.914), respectively. Furthermore, we predicted 34 potential compounds, including cyclosporine, oestrogen and so on, which may engage with hub genes and attenuate immune disorders instigated by PTE. The diagnostic performance of these biomarkers, alongside the interventional effect of cyclosporine, was further corroborated in animal studies via ELISA, Western blot and immunofluorescence assays. In summary, this study identifies a disturbance in the placental immune landscape, a secondary effect of PTE, which may underlie multiple pregnancy complications. Importantly, our research contributes to the noninvasive and timely detection of PTE-induced placental immune disorders, while also offering innovative therapeutic strategies for their treatment.

18.
J Biomed Inform ; 146: 104488, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37678485

RESUMEN

OBJECTIVE: To develop a hybrid neural network-based blood donation prediction method, via this predictive model, we can obtain the best estimate of whole blood in Beijing Tongzhou District Central Blood Station and help managers smoothly solve the allocation problem under fluctuating hospital demand and limited resources. METHOD: Inspired by the practical problems faced by blood stations providing transfusion services to several hospitals, a hybrid model based on a time-series prediction method and neural network, SARIMAX-TCN-LSTM is proposed for the prediction of daily whole blood donations. The experiment was performed at the central blood station in Tongzhou district, where we used whole blood donations from January 1, 2015, to November 14, 2021, as the subject, supplemented by meteorological and epidemic factors affecting blood donation, to predict daily blood donations for the next two weeks. RESULT: The hybrid model significantly outperformed the traditional time series forecasting method on multiple regression metrics, with twice as effective fitting as the baseline and a 33% reduction in Root Mean Squared Error (RMSE). Results indicate that the proposed model can improve the prediction accuracy of daily blood donations, and the co-validity of the structure was evidenced in an ablation experiment. CONCLUSION: Development and evaluation of a hybrid neural network-based model structure improve the prediction of daily blood donations. This intelligent forecasting method can help managers to overcome the challenges of sudden blood demand and contribute to the optimization of resource allocation tasks.

19.
Materials (Basel) ; 16(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37374442

RESUMEN

Metasurface-based research with phase-change materials has been a prominent and rapidly developing research field that has drawn considerable attention in recent years. In this paper, we proposed a kind of tunable metasurface based on the simplest metal-insulator-metal structure, which can be realized by the mutual transformation of insulating and metallic states of vanadium dioxide (VO2) and can realize the functional switching of photonic spin Hall effect (PSHE), absorption and beam deflection at the same terahertz frequency. When VO2 is insulating, combined with the geometric phase, the metasurface can realize PSHE. A normal incident linear polarized wave will be split into two spin-polarized reflection beams traveling in two off-normal directions. When VO2 is in the metal state, the designed metasurface can be used as a wave absorber and a deflector, which will completely absorb LCP waves, while the reflected amplitude of RCP waves is 0.828 and deflects. Our design only consists of one layer of artificial structure with two materials and is easy to realize in the experiment compared with the metasurface of a multi-layer structure, which can provide new ideas for the research of tunable multifunctional metasurface.

20.
J Control Release ; 358: 681-705, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37196900

RESUMEN

Gliomas are the most aggressive and lethal tumors of the central nervous system, for which few therapeutic options exist. Surgical resection is the primary treatment for most gliomas; however, tumor recurrence is nearly inevitable. Emerging nanobiotechnology-based strategies have shown great prospects for early glioma diagnosis, physiological barrier traversing, postoperative regrowth suppression, and microenvironment remodeling. Herein, we focus on the postoperative scenario and summarize the key properties of the glioma microenvironment, especially its immune peculiarities. We elucidate the challenges of managing recurrent glioma. We also discuss the potential of nanobiotechnology in addressing the therapeutic challenges of recurrent glioma, including optimizing the design of drug delivery systems, enhancing intracranial accumulation, and restoring the anti-glioma immune response. The development of these technologies offers new opportunities for accelerating the drug development process and treating recurrent glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Microambiente Tumoral
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