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To evaluate lenticular biomechanical and geometric parameters in Chinese adults with myopia and identify relevant factors using Brillouin microscopy (BM) and Pentacam. The biomechanical and geometric properties of the ocular lenses of Chinese adults with myopia were quantified using BM. Anterior segment images were acquired using a Pentacam. Correlated factors including age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), white-to-white ratio (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were analyzed. We studied 65 eyes from 65 participants (mean age, 25.23 ± 6.12 years). Width of Top Plateau (WTP), Width of Bottom Plateau (WBP), Slope of Anterior Cortex (SAC), Slope of Posterior Cortex (SPC), and Height of Plateau (Height) metrics obtained using BM showed mean values of 2.597 ± 0.393 mm, 4.310 ± 0.535 mm, 1.344 ± 0.549 GPa/mm, -1.343 ± 0.480 GPa/mm, and 3.373 ± 0.048 GPa, respectively. No significant correlation was found between these parameters and sex, SE, IOP, CCT, ACA, or Height. Interestingly, WBP (r = 0.467, P < 0.001), SAC (r = 0.412, P = 0.001), and SPC (r = -0.280, P = 0.024) were significantly associated with age, and an age-related increase of WBP (slope of 35.36 ± 10.08 µm per year) was identified. Both ACD and ACV showed significant correlations with SAC (r = 0.329 and 0.380, P = 0.008 and 0.002, respectively), but not with SPC. BM provided a novel perspective on lenticular biomechanical and geometric properties in Chinese adults with myopia, which correlated with age, AL, WTW, ACD, and ACV.
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During thermal deformation, grain coarsening due to grain growth and grain refinement resulting from dynamic recrystallization (DRX) collectively influence the deformed grain size. To investigate the separative and comprehensive effects of the two mechanisms in the Ni-38Cr-3.8Al alloy, grain growth experiments and isothermal compression tests were conducted. Kinetics models for grain growth and DRX behaviors were established based on the experimental data, which were integrated with finite element (FE) techniques to simulate the evolution of grain size throughout the entire thermal compression process. The effects of grain coarsening and grain refinement during this process were separated and quantified based on the simulation data. The results revealed that grain coarsening predominated during the heating and holding stages, with a longer holding time and higher holding temperatures intensifying this effect. However, during the compression stage, grain coarsening and grain refinement co-existed, and their competition was influenced by deformation parameters. Specifically, grain refinement dominated at strain rates exceeding 0.1 s-1, while grain coarsening dominated at lower strain rates (<0.1 s-1) and higher deformation temperatures (>1373 K). The simulated grain sizes closely matched the experimental observations.
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BACKGROUND: Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions. METHODS: We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3-18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models. RESULTS: The study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807-0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia. CONCLUSIONS: The XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3-18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.
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Miopía , Refracción Ocular , Adolescente , Niño , Preescolar , Humanos , Miopía/diagnóstico , Miopía/epidemiologíaRESUMEN
This study aimed to investigate the underlying pathophysiology of high myopia by analyzing the proteome of human corneal stromal lenticule samples obtained through small incision lenticule extraction (SMILE). A total of thirty-two patients who underwent SMILE were included in the study. Label-free quantitative proteomic analysis was performed on corneal stromal lenticule samples, equally representing high myopia (n = 10) and low myopia (n = 10) groups. The identified and profiled lenticule proteomes were analyzed using in silico tools to explore biological characteristics of differentially expressed proteins (DEPs). Additionally, LASSO regression and random forest model were employed to identify key proteins associated with the pathophysiology of high myopia. The DEPs were found to be closely linked to immune activation, extracellular matrix, and cell adhesion-related pathways according to gene ontology analysis. Specifically, decreased expression of COL1A1 and increased expression of CDH11 were associated with the pathogenesis of high myopia and validated by western blotting (n = 6) and quantitative real time polymerase chain reaction (n = 6). Overall, this study provides evidence that COL1A1 and CDH11 may contribute to the pathophysiology of high myopia based on comparative proteomic profiling of human corneal stromal lenticules obtained through SMILE.
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Cirugía Laser de Córnea , Miopía , Humanos , Proteómica , Sustancia Propia/metabolismo , Miopía/metabolismo , Láseres de ExcímerosRESUMEN
PURPOSE: To investigate the long-term preservation effects of nutrient capsules on the physiological activity, collagen fiber structure and transmittance of corneal stromal lenticules derived from small incision lenticule extraction (SMILE). METHODS: A new nutrient capsule was constructed for long-term preservation of SMILE-derived corneal stromal lenticules. The lenticules were randomly divided into 99% anhydrous glycerol, and hydrogel nutrient capsules. After preserving for 1 year at -80 °C, lenticules were compared with fresh lenticules. The optical transmittance, tissue morphology, ultrastructure, cells activity and immunogenicity of the lenticules was detected and compared between different groups. RESULTS: The rate of apoptotic cells was significantly higher in the glycerol group compared with the nutrient capsule group (P < 0.0001). More viable cells were present in the lenticules after nutrient capsule preservation compared to the glycerol group (P = 0.0003). The mean transmittance of the lenticules in the glycerol group (50 ± 18%) was significantly lower (P = 0.0008) compared to the control group (75 ± 11%), and the lenticules transmittance of the nutrient capsule group (64 ± 15%) after long-term preservation was not significantly different (P = 0.23) compared to the control group. The structure of HE staining showed that the collagen fibers in the nutrient capsule group were arranged in parallel and neatly, and a few cavitation vesicles were visible inside the tissue. There was no significant difference in the number of lenticular collagen fibers in the nutritional capsule group compared to the fresh lenticule group (P = 0.06). HLA-DR, HLA-ABC, CD45, CD25 and CD69 expression was low in all groups of lenticules after preservation. CONCLUSIONS: Nutrient capsules can preserve lenticules for a long time and maintain the transmission structure and cells activity of lenticules.
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Sustancia Propia , Glicerol , Glicerol/farmacología , Criopreservación , Colágeno/farmacología , Matriz ExtracelularRESUMEN
The microbiota is essential for the extraction of energy and nutrition from plant-based diets and may have facilitated primate adaptation to new dietary niches in response to rapid environmental shifts. In this study, metagenomic sequencing technology was used to analyze the compositional structure and functional differences of the gut microbial community of Francois' langurs (Trachypithecus francoisi) under different environmental and dietary conditions. The results showed that in terms of the composition of the gut microbial community, there were significant differences among the gut microbiota of Francois' langurs (anthropogenic disturbed populations, wild populations, and captive populations) under different environmental and dietary conditions. The microbial communities with the highest abundance in Francois' langurs were Firmicutes and Bacteroidetes. Firmicutes was the most abundant phylum in anthropogenic disturbed Francois' langurs and the least abundant in captive Francois' langurs. The abundance of Bacteroidetes was highest in captive Francois' langurs. In the analysis and comparison of alpha diversity, the diversity of the gut microbiota of Francois' langurs affected by anthropogenic disturbance was the highest. The significant differences in gut microbiota between Francois' langurs in different environments and different diets were further supported by principal coordinate analysis (PCoA), with the disturbance group having a gut microbiota more similar to the wild group. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation analysis indicated a high abundance of functional genes involved in carbohydrate metabolism, amino acid metabolism, replication and repair, cofactor and vitamin metabolism, and other amino acid metabolism pathways. Additionally, the functional genes involved in carbohydrate metabolism pathways were significantly enriched in the gut microbial community of Francois' langurs that were anthropogenic disturbed and captive. The gut microbiota of the Francois' langurs exhibited potential plasticity for dietary flexibility, and long-term food availability in captive populations leads to changes in gut microbiota composition and function. This study explored the composition and function of the gut microbiota of Francois' langurs and provided a scientific basis for understanding the physiological and health status of Francois' langurs, effectively protecting the population of wild Francois' langurs and reintroducing captive Francois' langurs into the wild.
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Heterostructured nanomaterials have arisen as electrocatalysts with great potential for hydrogen evolution reaction (HER), considering their superiority in integrating different active components but are plagued by their insufficient active site density in a wide pH range. In this report, double sulfur-vacancy-decorated CoS1.097@MoS2 core-shell heterojunctions are designed, which contain a primary structure of hollow CoS1.097 nanocubes and a secondary structure of ultrathin MoS2 nanosheets. Taking advantage of the core-shell type heterointerfaces and double sulfur-vacancy, the CoS1.097@MoS2 catalyst exhibits pH-universal HER performance, achieving the overpotentials at 10 mA cm-2 of 190, 139, and 220 mV in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS, respectively. Systematic theoretical results show that the double sulfur-vacancy can endow the CoS1.097@MoS2 core-shell heterojunctions with promoted electron/mass transfer and enhanced reactive kinetics, thus boosting HER performance. This work clearly demonstrates an indispensable role of double sulfur-vacancy in enhancing the electrocatalytic HER performance of core-shell type heterojunctions under a wide pH operating condition.
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Grain boundary engineering (GBE) is considered to be an attractive approach to microstructure control, which significantly enhances the grain-boundary-related properties of face-centered cubic (FCC) metals. During the twinning-related GBE, the microstructures are characterized as abundant special twin boundaries that sufficiently disrupt the connectivity of the random boundary network. However, controlling the grain boundary character distribution (GBCD) is an extremely difficult issue, as it strongly depends on diverse processing parameters. This article provides a comprehensive review of controlling GBCD during the twinning-related GBE of FCC materials. To commence, this review elaborates on the theory of twinning-related GBE, the microscopic mechanisms used in the optimization of GBCD, and the optimization objectives of GBCD. Aiming to achieve control over the GBCD, the influence of the initial microstructure, thermo-mechanical processing (TMP) routes, and thermal deformation parameters on the twinning-related microstructures and associated evolution mechanisms are discussed thoroughly. Especially, the development of twinning-related kinetics models for predicting the evolution of twin density is highlighted. Furthermore, this review addresses the applications of twinning-related GBE in enhancing the mechanical properties and corrosion resistance of FCC materials. Finally, future prospects in terms of controlling the GBCD during twinning-related GBE are proposed. This study will contribute to optimizing the GBCD and designing GBE routes for better grain-boundary-related properties in terms of FCC materials.
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Gut microbiota play an important role in impacting the host's metabolism, immunity, speciation, and many other functions. How sex and environment affect the structure and function of fecal microbiota in red deer (Cervus elaphus) is still unclear, particularly with regard to the intake of different diets. In this study, non-invasive molecular sexing techniques were used to determine the sex of fecal samples from both wild and captive red deer during the overwintering period. Fecal microbiota composition and diversity analyses were performed using amplicons from the V4-V5 region of the 16S rRNA gene sequenced on the Illumina HiSeq platform. Based on Picrust2 prediction software, potential function distribution information was evaluated by comparing the Kyoto Encyclopedia of Genes and Genome (KEGG). The results showed that the fecal microbiota of the wild deer (WF, n = 10; WM, n = 12) was significantly enriched in Firmicutes and decreased in Bacteroidetes, while the captive deer (CF, n = 8; CM, n = 3) had a significantly higher number of Bacteroidetes. The dominant species of fecal microbiota in the wild and captive red deer were similar at the genus level. The alpha diversity index shows significant difference in fecal microbiota diversity between the males and females in wild deer (p < 0.05). Beta diversity shows significant inter-group differences between wild and captive deer (p < 0.05) but no significant differences between female and male in wild or captive deer. The metabolism was the most important pathway at the first level of KEGG pathway analysis. In the secondary pathway of metabolism, glycan biosynthesis and metabolism, energy metabolism, and the metabolism of other amino acids were significantly different. In summary, these compositional and functional variations in the fecal microbiota of red deer may be helpful for guiding conservation management and policy decision-making, providing important information for future applications of population management and conservation.
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The spatiotemporal phase transformation during hot stamping would considerably effect the microstructure and mechanical properties of steels. In order to manufacture hot-stamping components of ultra-high-strength steel with tailored mechanical properties, the effect of the quenching time and the temperature of the die on the phase-transformation characteristics and mechanical property of ultra-high-strength steel was deeply studied. A finite element (FE) model coupled with a thermomechanical phase was employed to perform a succession of simulations for hot stamping corresponding to different quenching times and the temperatures of die, and the corresponding hot stamping experiments were performed. The 3D mapping surfaces of the temperature; quenching time; and three microstructures, namely austenite, bainite, and martensite, were constructed, and the mapping relationships in such surfaces were further explained by microstructural observations. Subsequently, based on the test results of the mechanical properties, the relationship curves of hardness and tensile strength, hardness, and elongation at break were fitted respectively, and then the 3D mapping surfaces were constructed for hardness, tensile strength, and elongation at break, which varied with the temperature die and quenching time. Finally, the quenching parameters of the automobile B-pillar were designed according to the constructed mapping relationship, and the hot-stamping FE simulation of the automobile B-pillar was developed. The result shows that those constructed mapping surfaces are helpful for adjusting the local mechanical property of the steels by designing the parameters.
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In thermal deformation of materials, grain refinement induced by dynamic recrystallization (DRX) is often pursued to obtain excellent mechanical properties. Here, the thermal deformation behaviors of SAE 5137H steel were investigated and characterized at temperature and strain rate range of 1123-1483 K and 0.01-10 s-1. Meanwhile, a design approach in speed-loading paths for grain refinement during current-heating compression was proposed, and these paths are linked to a typical three-dimensional (3D) response surface. Depending on the acquired stress-strain curves, the flow behaviors of this steel were analyzed and the typical 3D processing map was constructed to clarify the stable processing parameter domains during the continuous deformation process. Then, by the typical 3D processing map and microstructure observation, the 3D deformation mechanism map was constructed to connect the processing parameters and microstructural mechanisms. Subsequently, the 3D activation energy map was constructed to evaluate these deformation mechanisms, and the enhanced deformation mechanism map was constructed. Eventually, based on the enhanced deformation mechanism map, the speed-loading paths for SAE 5137H steel during current-heating compression were designed and they are mapped in a 3D response surface.
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BACKGROUND: CD103+CD8+ tissue-resident memory T (TRM) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT). METHODS: Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103+CD8+ TRM cells. RESULTS: Patients with high CD103+CD8+ TRM cells infiltration, but not CD8+ T cells, are more likely to benefit from immunotherapy and ACT. The presence of TRM cells is highly associated with an enhanced IFNγ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103+CD8+ TRM cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients. CONCLUSIONS: CD103+CD8+ TRM cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients.
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Neoplasias de la Vejiga Urinaria , Linfocitos T CD8-positivos , Humanos , Memoria Inmunológica , Linfocitos Infiltrantes de Tumor , Células T de Memoria , Músculos/metabolismo , Músculos/patología , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
BACKGROUND: This study aims to reveal the clinical significance of stromal-infiltrating tumor-associated macrophages (TAMs) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: This study included 288 patients from the TCGA database and 118 patients from Fudan University Shanghai Cancer Center with MIBC. The CIBERSORT model and immunohistochemistry were used to evaluate TAM infiltration. Cox regression analyses were employed to calculate their prognostic value. RESULTS: Among all 23 immune phenotypes analyzed in the TCGA cohort, pan-macrophage infiltration was significantly associated with poor prognosis (p = 0.001). Further analyses found that stromal TAM infiltration could be an independent prognostic predictor for recurrence-free survival (RFS; HR: 1.019, 95% CI: 1.006-1.033, p = 0.004). High stromal infiltration was related to unfavorable RFS. After stratification by adjuvant chemotherapy (ACT), patients without ACT could be differentiated by TAM infiltration (p = 0.036), while patients with ACT could not. Moreover, TAM infiltration was negatively associated with IFN-γ-related mRNA panel, which was shown to have strong predictive value for clinical response to programmed death-1 (PD-1) inhibition. CONCLUSIONS: Stromal TAM infiltration could be an independent prognosticator for MIBC patients. This might have potential to guide precise treatments such as ACT and immune checkpoint blockade in MIBC.
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Neoplasias de la Vejiga Urinaria , China , Humanos , Músculos , Pronóstico , Macrófagos Asociados a Tumores , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
BACKGROUND: TIGIT and PD-1 are checkpoint receptors that could regulate the functional status of immune cells through independent pathways. However, the clinical significance of immune classification based on TIGIT and PD-1 expression remains unclear in muscle-invasive bladder cancer (MIBC). METHODS: Patients with MIBC from four independent cohorts were categorised into three clusters. Survival analysis conducted through Kaplan-Meier curves and Cox regression model. Immune contexture was measured by immunohistochemistry and CIBERSORT algorithm. Twenty-five fresh tumour tissue samples were utilised to evaluate functional state of CD8+ T cells by flow cytometry. RESULTS: Cluster I (TIGITlowPD-1low) contained widely poor immune infiltrates with higher FGFR3 mutation, Cluster II (TIGITlowPD-1high) exhibited a highly infiltrated contexture with increased cytolytic CD8+ T cells and had the best prognosis, Cluster III (TIGIThigh) presented a suppressive tumour microenvironment (TME) featured by exhausted CD8+ T cells and basal molecular subtype. Patients of Cluster III had the worst survival but could benefit more from adjuvant chemotherapy and anti-PD-L1 immunotherapy, and also presented limited FGFR3 signalling signature but activated immunotherapeutic and EGFR-associated pathway. CONCLUSIONS: TIGIT/PD-1-based risk stratification with distinct immune and molecular features could be served as a predictor for systematic therapeutic response including adjuvant chemotherapy and immunotherapy in MIBC patients.
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Neoplasias de la Vejiga Urinaria , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Músculos/metabolismo , Músculos/patología , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Receptores Inmunológicos/genética , Estudios Retrospectivos , Microambiente Tumoral/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Immune checkpoint blockade (ICB) and adjuvant chemotherapy (ACT) have shown clinical benefit in muscle-invasive bladder cancer (MIBC) with only a few predictive biomarkers identified so far. Neuropilin-1 (NRP1) has been identified as a key immune checkpoint and a novel immunotherapeutic target but the clinical significance of NRP1 remains unclear in MIBC. METHODS: Three independent cohorts were involved in our study: IMvigor210 Cohort (n = 348), The Cancer Genome Atlas Cohort (TCGA, n = 391), and Zhongshan Hospital Cohort (ZSHS, n = 130). Parallel detection and validation of risk stratification based on NRP1 expression were executed in patients treated with anti-PD-L1 agent and adjuvant chemotherapy (ACT). RESULTS: NRP1 expression conferred poor survival and predicted response to both PD-L1 blockade and cisplatin-based ACT in MIBC. Further exploration revealed high-level NRP1 was extremely associated with infiltration of exhausted CD8+ T cells, immature NK cells and M2 polarized tumor-associated macrophages in MIBC patients. Moreover, elevated NRP1 expression was also correlated with low mutation burden and reduced mutation in cell cycle pathway. CONCLUSIONS: Our study firstly identified and validated the clinical implications of NRP1 expression for prognosis and systematic therapeutic responses (PD-L1 blockade and ACT) in MIBC. NRP1 expression was associated with an immunosuppressive microenvironment with dysfunctional effector immune cells. Prospective investigations of its roles in the therapeutic landscape of MIBC warrant more consideration.
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Neuropilina-1 , Neoplasias de la Vejiga Urinaria , Linfocitos T CD8-positivos , Humanos , Músculos/metabolismo , Invasividad Neoplásica , Neuropilina-1/genética , Pronóstico , Estudios Prospectivos , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: Muscle-invasive bladder cancer (MIBC) is an aggressive and heterogeneous malignancy. Tumor-associated macrophages (TAMs) are key infiltrating cell populations in the inflammatory microenvironment of malignant tumors including MIBC. It intrigues us to explore the clinical significance and immunoregulatory role of TAMs infiltration and polarization in MIBC. METHODS: A total of 141 patients with MIBC from Zhongshan Hospital and 391 patients with MIBC from The Cancer Genome Atlas (TCGA) database were included in this study. Moreover, 195 patients who received anti-PD-L1 therapy from the IMvigor210 trial were enrolled. Patients were categorized into three subtypes considering the infiltration level and polarization status of TAMs, denoted as TAMlow (Subtype I), TAMhigh&M2/M1low (Subtype II), and TAMhigh&M2/M1high (Subtype III). RESULTS: Subtype III suffered inferior prognosis, and Subtype II could benefit more from adjuvant chemotherapy (ACT). Subtype III was featured with increased pro-tumor cells and immunosuppressive cytokines, while Subtype II possessed more immunogenic cells infiltration with activated and tumoricidal properties. Subtype II and Subtype III presented basal/squamous-like characterization and showed additional prognostic merit beyond molecular classification. Subtype I exhibited elevated level of FGFR3 signature, while Subtype II had EGFR signaling activation and immunotherapeutic indication. Additionally, Subtype II patients were indeed highly sensitive to PD-L1 blockade therapy in IMvigor210 trial. CONCLUSION: The infiltration and polarization status of TAMs shaped distinct immune microenvironment with predictive significance for survival outcome, ACT benefit, and PD-L1 blockade therapy sensitivity in MIBC. Immune classification based on TAMs polarization and infiltration might provide tools to tailor chemotherapy and immunotherapy.
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Neoplasias de la Vejiga Urinaria , Antígeno B7-H1/uso terapéutico , Humanos , Músculos/patología , Pronóstico , Microambiente Tumoral , Macrófagos Asociados a Tumores , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
BACKGROUND: Latency-associated peptide (LAP) was identified as crucial immune regulator in tumor microenvironment (TME) in recent researches. In this study, we aimed to estimate the predictive value of LAP expression for clinical survival and therapeutic response in muscle-invasive bladder cancer (MIBC). METHODS: Our study encompassed 140 MIBC patients from Zhongshan Hospital (ZSHS cohort), 401 patients from The Cancer Genome Atlas (TCGA cohort) and 195 patients received PDL1 blockade from IMvigor210 trial. Survival analyses were conducted through Kaplan-Meier curve and Cox regression model. LAP expression and its association with immune contexture were evaluated in ZSHS and TCGA cohort. RESULTS: We found that high intratumoral LAP+ cells infiltration anticipated inferior survival and adjuvant chemotherapy (ACT) response, and was closely related to an immunoevasive contexture with increased M2 macrophages, neutrophils and conspicuously a cluster of highly exhausted CD8+ T cells. The combinational analysis of LAP+ cells and CD8+ T cells infiltration stratified patients into distinct risk groups with implications for therapeutic sensitivity to PDL1 blockade and refinement of molecular classification in MIBC. CONCLUSIONS: LAP expression was correlated with patients' inferior prognosis, ACT-tolerance and an immunoevasive TME with exhausted CD8+ T cell infiltration, suggesting that LAP could serve as a promising therapeutic target in MIBC. Simultaneously, our novel TME classification based on LAP+ cells and CD8+ T cells infiltration and its potential in appraising PDL1 blockade application for MIBC patients deserved further validation.
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Linfocitos T CD8-positivos/inmunología , Quimioterapia Adyuvante/mortalidad , Resistencia a Antineoplásicos , Neoplasias de los Músculos/patología , Péptidos/metabolismo , Precursores de Proteínas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/patología , Estudios de Seguimiento , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias de los Músculos/tratamiento farmacológico , Neoplasias de los Músculos/inmunología , Neoplasias de los Músculos/metabolismo , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Escape del Tumor , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
In order to obtain the desired mechanical properties of products, an innovative method of loading parameter designs for acquiring the desired grain refinement is proposed, and it has been applied in the compression process of Ni80A superalloy. The deformation mechanism maps derived from processing maps based on the Dynamic Materials Model (DMM) theory were constructed, since the critical indicator values corresponding to dynamic recrystallization (DRX) and dynamic recovery (DRV) mechanisms were determined. The processing-parameter domains with DRX mechanisms were separated from the deformation mechanism map, while such domains were chaotic and difficult to apply in innovative parameter loading path design. The speed-loading path derived from strain rate-loading path in a compression process was pursued. The grain refinement domains are discretized into a finite series of sub-domains with clear processing parameters, and the optimal strain rate of each sub-domain is determined by step-by-step finite element simulation. A 3D response surface of the innovative optimal loading path of strain rate was fitted by interpolating methods. Finally, the isothermal compression experiments for Ni80A superalloy were conducted, and the microstructure observations indicated that the desired grain refinement was achieved. This innovative method of parameter loading path design contributes to the microstructure adjustment of the alloys with DRX mechanism.
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Single-scale frameworks are often used to analyze the habitat selections of species. Research on habitat selection can be significantly improved using multi-scale models that enable greater in-depth analyses of the scale dependence between species and specific environmental factors. In this study, the winter habitat selection of red deer in the Gogostaihanwula Nature Reserve, Inner Mongolia, was studied using a multi-scale model. Each selected covariate was included in multi-scale models at their "characteristic scale", and we used an all subsets approach and model selection framework to assess habitat selection. The results showed that: (1) Univariate logistic regression analysis showed that the response scale of red deer to environmental factors was different among different covariate. The optimal scale of the single covariate was 800-3200 m, slope (SLP), altitude (ELE), and ratio of deciduous broad-leaved forests were 800 m in large scale, except that the farmland ratio was 200 m in fine scale. The optimal scale of road density and grassland ratio is both 1600 m, and the optimal scale of net forest production capacity is 3200 m; (2) distance to forest edges, distance to cement roads, distance to villages, altitude, distance to all road, and slope of the region were the most important factors affecting winter habitat selection. The outcomes of this study indicate that future studies on the effectiveness of habitat selections will benefit from multi-scale models. In addition to increasing interpretive and predictive capabilities, multi-scale habitat selection models enhance our understanding of how species respond to their environments and contribute to the formulation of effective conservation and management strategies for ungulata.
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In this study, the complete mitochondrial genome (mt DNA) of Amur Moose (Alces alces cameloides) was sequenced, using muscle tissue obtained from a male Amur moose. The total length of the mitochondrial genome is 16,305 bp. The genome structure of Amur moose is similar to other moose and it contains 12S rRNA gene, 16S rRNA gene, 22 tRNA genes, 13 protein-coding genes, and 1 control region.