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Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified. The risk variants found in the cases cause loss of function and result in a â¼10-fold increased odds of acquiring a myeloid malignancy. Partial CTR9 loss of function expands human hematopoietic stem cells (HSCs) by increased super elongation complex-mediated transcriptional activity, which thereby increases the expression of key regulators of HSC self-renewal. By following up on insights from a human genetic study examining inherited predisposition to the myeloid malignancies, we define a previously unknown antagonistic interaction between the PAF1 and super elongation complexes. These insights could enable targeted approaches for blood cancer prevention.
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Neoplasias Hematológicas , Fosfoproteínas , Elongación de la Transcripción Genética , Factores de Transcripción , Humanos , Neoplasias Hematológicas/genética , Células Madre Hematopoyéticas/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/genética , Fosfoproteínas/genéticaRESUMEN
The µ-opioid receptor (µOR) is an important target for pain management1 and molecular understanding of drug action on µOR will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance and single-molecule fluorescence resonance energy transfer, how ligand-specific conformational changes of µOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several conformations of the cytoplasmic face of the receptor that interconvert on different timescales, including a pre-activated conformation that is capable of G-protein binding, and a fully activated conformation that markedly reduces GDP affinity within the ternary complex. Interaction of ß-arrestin-1 with the µOR core binding site appears less specific and occurs with much lower affinity than binding of Gi.
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Ligandos , Conformación Proteica , Receptores Opioides mu , Humanos , beta-Arrestina 1/química , beta-Arrestina 1/metabolismo , Sitios de Unión , Transferencia Resonante de Energía de Fluorescencia , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/química , Guanosina Difosfato/metabolismo , Guanosina Difosfato/química , Modelos Moleculares , Unión Proteica , Receptores Opioides mu/metabolismo , Receptores Opioides mu/química , Imagen Individual de MoléculaRESUMEN
Extracellular vesicle (EV) molecular phenotyping offers enormous opportunities for cancer diagnostics. However, the majority of the associated studies adopted biomarker-based unimodal analysis to achieve cancer diagnosis, which has high false positives and low precision. Herein, we report a multimodal platform for the high-precision diagnosis of bladder cancer (BCa) through a multispectral 3D DNA machine in combination with a multimodal machine learning (ML) algorithm. The DNA machine was constructed using magnetic microparticles (MNPs) functionalized with aptamers that specifically identify the target of interest, i.e., five protein markers on bladder-cancer-derived urinary EVs (uEVs). The aptamers were hybridized with DNA-stabilized silver nanoclusters (DNA/AgNCs) and a G-quadruplex/hemin complex to form a sensing module. Such a DNA machine ensured multispectral detection of protein markers by fluorescence (FL), inductively coupled plasma mass spectrometry (ICP-MS), and UV-vis absorption (Abs). The obtained data sets then underwent uni- or multimodal ML for BCa diagnosis to compare the analytical performance. In this study, urine samples were obtained from our prospective cohort (n = 45). Our analytical results showed that the 3D DNA machine provided a detection limit of 9.2 × 103 particles mL-1 with a linear range of 4 × 104 to 5 × 107 particles mL-1 for uEVs. Moreover, the multimodal data fusion model exhibited an accuracy of 95.0%, a precision of 93.1%, and a recall rate of 93.2% on average, while those of the three types of unimodal models were no more than 91%. The elevated diagnosis precision by using the present fusion platform offers a perspective approach to diminishing the rate of misdiagnosis and overtreatment of BCa.
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Aprendizaje Automático , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/orina , Humanos , Biomarcadores de Tumor/orina , Biomarcadores de Tumor/análisis , ADN/química , Plata/química , Aptámeros de Nucleótidos/química , Vesículas Extracelulares/química , Nanopartículas del Metal/químicaRESUMEN
Human bronchial epithelial cells in the airway system, as the primary barrier between humans and the surrounding environment, assume a crucial function in orchestrating the processes of airway inflammation. Target to develop a new three-dimensional (3D) inflammatory model to airway system, and here we report a strategy by using self-assembling D-form peptide to cover the process. By testing physicochemical properties and biocompatibility of Sciobio-â ¢, we confirmed that it can rapidly self-assembles under the trigger of ions to form a 3D nanonetwork-like scaffold, which supports 3D cell culture including the cell strains like BEAS-2B cells. Subsequently, inflammation model was established by lipopolysaccharide (LPS), the expression of some markers of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-8 (IL-8), the levels of relevant inflammatory factors were measured by RT-qPCR and the secretion profile of inflammatory cytokines by ELISA, are obtained the quite difference effects in 2D and 3D microenvironment, which suggested Sciobio-â ¢ hydrogel is an ideal scaffold that create the microenvironment for 3D cell culture. Here we are success to establish a 3D inflammation model for airway system. This innovative model allows for rapid and accurate evaluation of drug metabolism and toxicological side effects, hope to use in drug screening for airway inflammatory diseases and beyond.
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Bronquios , Inflamación , Humanos , Inflamación/metabolismo , Células Cultivadas , Interleucina-1beta/metabolismo , Células Epiteliales/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Single-cell arrays have emerged as a versatile method for executing single-cell manipulations across an array of biological applications. In this paper, an innovative microfluidic platform is unveiled that utilizes optoelectronic tweezers (OETs) to array and sort individual cells at a flow rate of 20 µL min-1. This platform is also adept at executing dielectrophoresis (DEP)-based, light-guided single-cell retrievals from designated micro-wells. This presents a compelling non-contact method for the rapid and straightforward sorting of cells that are hard to distinguish. Within this system, cells are individually confined to micro-wells, achieving an impressive high single-cell capture rate exceeding 91.9%. The roles of illuminating patterns, flow velocities, and applied electrical voltages are delved into in enhancing the single-cell capture rate. By integrating the OET system with the micro-well arrays, the device showcases adaptability and a plethora of functions. It can concurrently trap and segregate specific cells, guided by their dielectric signatures. Experimental results, derived from a mixed sample of HepG2 and L-O2 cells, reveal a sorting accuracy for L-O2 cells surpassing 91%. Fluorescence markers allow for the identification of sequestered, fluorescence-tagged HepG2 cells, which can subsequently be selectively released within the chip. This platform's rapidity in capturing and releasing individual cells augments its potential for future biological research and applications.
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Pinzas Ópticas , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Análisis de la Célula Individual/instrumentación , Humanos , Separación Celular/instrumentación , Separación Celular/métodos , Microfluídica/métodos , Microfluídica/instrumentaciónRESUMEN
PURPOSE: The detrimental effects of pathological angiogenesis on the visual function are indisputable. Within a prominent role in chromosome segregation and tumor progression, aurora kinase B (AURKB) assumes a prominent role. However, its role in pathological retinal angiogenesis remains unclear. This study explores this latent mechanism. METHODS: To inhibit AURKB expression, we designed specific small interfering RNAs targeting AURKB and transfected them into vascular endothelial cells. Barasertib was selected as the AURKB inhibitor. The anti-angiogenic effects of both AURKB siRNA and barasertib were assessed in vitro by cell proliferation, transwell migration, and tube formation. To evaluate the angiogentic effects of AURKB in vivo, neonatal mice were exposed to 75% oxygen followed by normoxic repositioning to establish an oxygen-induced retinopathy (OIR) model. Subsequently, phosphate-buffered saline and barasertib were administered into OIR mice via intravitreal injection. The effects of AURKB on cell cycle proteins were determined by western blot analysis. RESULTS: We found that AURKB was overexpressed during pathological angiogenesis. AURKB siRNA and barasertib significantly inhibited endothelial cell proliferation, migration, and tube formation in vitro. Furthermore, AURKB inhibition attenuated retinal angiogenesis in the OIR model. A possible mechanism is the disruption of cell cycle by AURKB inhibition. CONCLUSION: In conclusion, AURKB significantly influenced pathological retinal angiogenesis, thereby presenting a promising therapeutic target in ocular neovascular diseases.
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Organofosfatos , Quinazolinas , Enfermedades de la Retina , Neovascularización Retiniana , Animales , Ratones , Angiogénesis , Aurora Quinasa B/antagonistas & inhibidores , Aurora Quinasa B/metabolismo , División Celular , Proliferación Celular , Células Endoteliales/metabolismo , Ratones Endogámicos C57BL , Neovascularización Patológica , Oxígeno , Neovascularización Retiniana/metabolismo , ARN Interferente Pequeño/uso terapéuticoRESUMEN
In this study, a 4-(hydroxymethyl)-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane 1-oxide (PEPA)-functionalized acrylate monomer, PEPAA, is designed and utilized for the synthesis of macromolecular flame retardants poly(PEPAA-co-AM) with varying PEPAA/AM ratio through copolymerization with acrylamide (AM). The poly(PEPAA-co-AM) is then incorporated into polypropylene (PP) to prepare PP/poly(PEPAA-co-AM) composites. The flame retardant effect of poly(PEPAA-co-AM) on PP is investigated using cone calorimetric test (CCT), and compared with that of PEPAA homopolymer (P-PEPAA), AM homopolymer (PAM), and blends of P-PEPAA/PAM. The results demonstrate that, in comparison with P-PEPAA, PAM, and blends of P-PEPAA/PAM, the incorporation of poly(PEPAA-co-AM) significantly enhances the flame retardancy of PP. Notably, the best flame retardancy is achieved when the ratio of PEPAA/AM copolymerization in poly(PEPAA-co-AM) is 2/8. The morphology and composition of residual chars from combustion are analyzed using SEM-EDS while the residual graphitization degree is examined through Raman spectroscopy. Additionally, TG-FTIR-MS is utilized to investigate the pyrolysis products in gas phase during thermal decomposition of poly(PEPAA-co-AM). Based on these experimental results, a flame retardant mechanism for poly(PEPAA-co-AM) is proposed. The PP/poly(PEPAA-co-AM) composites not only retain the excellent processing properties of pure PP but also exhibit enhanced mechanical properties.
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PURPOSE: Lacrimal gland (LG) adenocarcinomas (ACs) are rare, with limited data. We compared clinicopathologic features and local recurrence, distant metastasis, and survival rates between LG AC and LG adenoid cystic carcinoma (ACC). METHODS: The records of LG AC patients treated from 2008 to 2022 and LG ACC patients treated from 1998 to 2022 at the same center were retrospectively reviewed. RESULTS: The study included 20 patients with AC; 10 de-novo AC, 10 ex-pleomorphic AC; and 51 ACC patients. The median age at diagnosis was 61 years for de-novo AC, 54 years for ex-pleomorphic AC, and 45 years for ACC. All groups had male predominance. The initial T category was T2 in 50% (5/10) of de-novo ACs; 60% (6/10) of ex-pleomorphic ACs; and 59% (30/51) of ACCs. Perineural invasion was present in 33% (5/15) of ACs and 90% (45/50) of ACCs ( p < 0.001). Of the 20 AC patients, 14 had eye-sparing surgery; 4 had orbital exenteration; and 2 had unresectable disease. All AC patients received postoperative radiotherapy and 15 (75%) received concurrent chemotherapy. Fourteen AC patients were tested for human growth factor receptor 2 expression, and 10 (71%) were human growth factor receptor 2 positive; 5 received human growth factor receptor 2-targeted therapy. AC and ACC had similar 5-year recurrence rates (20% and 33%, respectively, p = 0.31) and metastasis rates (20% and 34%, respectively, p = 0.30). de-novo AC, ex-pleomorphic AC, and ACC had similar 5-year disease-specific survival rates (80%, 79%, and 81%, respectively, p > 0.99). CONCLUSIONS: LG AC and ACC have similar baseline clinicopathologic features, except that perineural invasion is more common in ACC, and similar recurrence, metastasis, and survival rates. Human growth factor receptor 2-targeted therapy may be appropriate in some patients with LG AC.
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Adenocarcinoma , Carcinoma Adenoide Quístico , Neoplasias del Ojo , Enfermedades del Aparato Lagrimal , Humanos , Masculino , Carcinoma Adenoide Quístico/terapia , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/patología , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Enfermedades del Aparato Lagrimal/terapia , Enfermedades del Aparato Lagrimal/diagnóstico , Enfermedades del Aparato Lagrimal/patología , Neoplasias del Ojo/terapia , Neoplasias del Ojo/patología , Neoplasias del Ojo/diagnóstico , Anciano , Adulto , Adenocarcinoma/terapia , Adenocarcinoma/patología , Recurrencia Local de Neoplasia , Tasa de Supervivencia , Anciano de 80 o más Años , Aparato Lagrimal/patologíaRESUMEN
OBJECTIVE: To develop a machine learning diagnostic model based on MMP7 and other serological testing indicators for early and efficient diagnosis of biliary atresia (BA). METHODS: A retrospective analysis was conducted on patient information from those hospitalized for pathological jaundice at Beijing Children's Hospital between January 1, 2019, and December 31, 2023. Patients with serum MMP7, liver stiffness measurements, and other routine serological tests were included in the study. Six machine learning models were constructed, including logistic regression (LR), random forest (RF), decision tree (DET), support vector machine classifier (SVC), neural network (MLP), and extreme gradient boosting (XGBoost), to diagnose BA. The area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the various models. RESULTS: A total of 98 patients were included in the study, comprising 64 BA patients and 34 patients with other cholestatic liver diseases. Among the six machine learning models, the XGBoost algorithm model and RF algorithm model achieved the best predictive performance, with an AUROC of nearly 100% in both the training and validation sets. In the training set, these two algorithm models achieved an accuracy, precision, recall, F1 score, and AUROC of 1. Through model interpretation analysis, serum MMP7 levels, serum GGT levels, and acholic stools were identified as the most important indicators for diagnosing BA. The nomogram constructed based on the XGBoost algorithm model also demonstrated convenient and efficient diagnostic efficacy. CONCLUSION: Machine learning models, especially the XGBoost algorithm and RF algorithm models, constructed based on preoperative serum MMP7 and serological tests can diagnose BA more efficiently and accurately. The most important influencing factors for diagnosis are serum MMP7, serum GGT, and acholic stools.
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Atresia Biliar , Aprendizaje Automático , Metaloproteinasa 7 de la Matriz , Humanos , Atresia Biliar/diagnóstico , Atresia Biliar/sangre , Estudios Retrospectivos , Masculino , Femenino , Lactante , Metaloproteinasa 7 de la Matriz/sangre , Pruebas Serológicas/métodos , Curva ROC , Biomarcadores/sangre , PreescolarRESUMEN
Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self-assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable ß-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science.
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Mucosa Gástrica , Hidrogeles , Péptidos , Factor Trefoil-3 , Hidrogeles/química , Factor Trefoil-3/química , Factor Trefoil-3/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/lesiones , Péptidos/química , Péptidos/farmacología , Animales , Humanos , Sistemas de Liberación de Medicamentos , Ratones , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Phase control over cation exchange (CE) reactions has emerged as an important approach for the synthesis of nanomaterials (NMs). Although factors such as crystal structure and morphology have been studied for the phase engineering of CE reactions in NMs, there remains a lack of systematic investigation to reveal the impact factors in heterogeneous materials. Herein, we report a molybdenum disulfide induced phase control method for synthesizing multidimensional Co3S4-MoS2 heteronanostructures (HNs) via cation exchange. MoS2 in parent Cu1.94S-MoS2 HNs are proved to affect the thermodynamics and kinetics of CE reactions, and facilitate the formation of Co3S4-MoS2 HNs with controlled phase. This MoS2 induced phase control method can be extended to other parent HNs with multiple dimensions, which shows its universality. Further, theoretical calculations demonstrate that Co3S4 (111)/MoS2 (001) exhibits a higher adhesion work, providing further evidence that MoS2 enables phase control in the HNs CE reactions, inducing the generation of novel Co3S4-MoS2 HNs. As a proof-of-concept application, the obtained Co3S4-MoS2 heteronanoplates (HNPls) show remarkable performance in hydrogen evolution reactions (HER) under alkaline media. This synthetic methodology provides a unique way to control the crystal structure and fills the gap in the study of heterogeneous materials on CE reaction over phase engineering.
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The formation of soil in karst ecosystem has always been a scientific problem of great concern to human beings. Algae can grow on the exposed and non-nutrition carbonate surface, inducing and accelerating weathering of rock substrates, thus promoting soil formation. Yet the actual contribution of algae to solutional weathering intensity remains unclear. In this study, we performed weathering simulation experiment on two algae species (Klebsormidium dissectum (F.Gay) H.Ettl & G.Gärtner and Chlorella vulgaris Beijerinck), which were screened from carbonated rock surfaces from a typical karst region in South China. The results showed: (1) both algae have solutional weathering effect on carbonate rock, (2) there is no difference of solutional intensity observed, yet the solutional modes are different, suggesting different ecological adaptative strategies, (3) algae on carbonate rocks have higher carbonic anhydrase activity (CAA) and secrete more extracellular polysaccharide (EPS), accelerating rock weathering. (4) The absolute dissolution amount of carbonate rock with algae participation is 3 times of that of without algae. These results indicate the significant impact of terrestrial algae on carbonate rock solutional weathering and provides quantitative evidence that terrestrial algae are pioneer species. It also contributes to our further understanding of soil formation in karst ecosystems in South China.
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Most insects, including human-targeting mosquitoes, detect odors through odorant-activated ion channel complexes consisting of a divergent odorant-binding subunit (OR) and a conserved co-receptor subunit (Orco). As a basis for understanding how odorants activate these heteromeric receptors, we report here cryo-electron microscopy structures of two different heteromeric odorant receptor complexes containing ORs from disease-vector mosquitos Aedes aegypti or Anopheles gambiae. These structures reveal an unexpected stoichiometry of one OR to three Orco subunits. Comparison of structures in odorant-bound and unbound states indicates that odorant binding to the sole OR subunit is sufficient to open the channel pore, suggesting a mechanism of OR activation and a conceptual framework for understanding evolution of insect odorant receptor sensitivity.
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Aedes , Anopheles , Microscopía por Crioelectrón , Proteínas de Insectos , Odorantes , Receptores Odorantes , Animales , Aedes/fisiología , Anopheles/fisiología , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Multimerización de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Receptores Odorantes/química , Receptores Odorantes/metabolismoRESUMEN
Birefringent materials with high optical anisotropy have been identified as a research hotspot owing to their significant scientific and technological significance in modern optoelectronics for manipulating light polarization. Researchers studying borate systems have discovered that adding π-conjugated units placed in parallel can significantly increase the birefringence of crystalline solids; some examples include [BO3] units, [B2O5] units, and [B3O6] units. However, there are not many borates with strictly parallel configurations of π-conjugated [B2O5] units. In this study, a new bimetallic borate Sr2Cd4(B2O5)3 with near-parallel arrangement of π-conjugated [B2O5] units was discovered. Sr2Cd4(B2O5)3 possesses the maximum number density of [B2O5] units, shortest dihedral angle of [B2O5] units (between the two [BO3]), and largest degree of [CdO6] octahedral distortion among all the currently known Sr-Cd-B-O tetragonal system borates, making it demonstrate a large birefringence of 0.102 at 532 nm. Theoretical analysis proves that π-conjugated [B2O5] anions are the primary source of the large birefringence of Sr2Cd4(B2O5)3.
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The Diels-Alder (D-A) reaction between furan and maleimide is a thermally reversible reaction that has become a vital chemical technique for designing polymer structures and functions. The kinetics of this reaction, particularly in polymer bulk states, have significant practical implications. In this study, we investigated the feasibility of utilizing infrared spectroscopy to measure the D-A reaction kinetics in bulk-state polymer. Specifically, we synthesized furan-functionalized polystyrene and added a maleimide small-molecule compound to form a D-A adduct. The intensity of the characteristic absorption peak of the D-A adduct was quantitatively measured by infrared spectroscopy, and the dependence of conversion of the D-A reaction on time was obtained at different temperatures. Subsequently, the D-A reaction apparent kinetic coefficient kapp and the Arrhenius activation energy Ea,D-A were calculated. These results were compared with those determined from 1H-NMR in the polymer solution states.
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Rapid advancements in human-machine interaction and voice biometrics impose desirability on soft mechanical sensors for sensing complex dynamic signals. However, existing soft mechanical sensors mainly concern quasi-static signals such as pressure and pulsation for health monitoring, limiting their applications in emerging wearable electronics. Here, we propose a hydrogel-based soft mechanical sensor that enables recording a wide range of dynamic signals relevant to humans by combining a preloading design strategy and iontronic sensing mechanism. The proposed sensor offers a two-orders-of-magnitude larger working bandwidth (up to 1000 Hz) than most of the reported soft mechanical sensors and meanwhile provides a high sensitivity (-23 dB) that surpasses the common commercial microphone. The amplitude-frequency characteristic of the proposed sensor can be precisely tuned to meet the desired requirement by adjusting the preloads and the parameters of the microstructured hydrogel. The sensor is capable of recording instrumental sounds with high fidelity from simple pure tones to melodic songs. Demonstration of a skin-mountable sensor used for human-voice-based remote control of a toy car shows great potential for applications in the voice user interface of human-machine interactions.
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Uveal melanoma (UVM) prognosis and the possibilities for targeted therapy depend on a thorough understanding of immune infiltration features and the analysis of genomic and immune signatures. Leveraging multi-omics data from The Cancer Genome Atlas and GEO datasets, we employed an unsupervised clustering algorithm to categorize UVM into immune-related subgroups. Subsequent multi-omics analysis revealed two distinct UVM subtypes, each characterized by unique genomic mutations and immune microenvironment disparities. The aggressive UMCS2 subtype exhibited higher TNM stage and poorer survival, marked by elevated metabolism and increased immune infiltration. However, UMCS2 displayed heightened tumor mutational burden and immune dysfunction, leading to reduced responsiveness to immunotherapy. Importantly, these subtypes demonstrated differential sensitivity to targeted drugs due to significant variances in metabolic and immune environments, with UMCS2 displaying lower sensitivity. We developed a robust, subtype-specific marker-based risk scoring system. This system's diagnostic accuracy was validated through ROC curves, decision curve analysis, and calibration curves, all yielding satisfactory results. Additionally, cell experiments identified the pivotal function of HTR2B, the most crucial factor in this risk model. Knocking down HTR2B significantly reduced the activity, proliferation, and invasion ability of the UVM cell line. These findings underscored the impact of gene and immune microenvironment alterations in driving distinct molecular subtypes, emphasizing the need for precise treatment strategies. The molecular subtyping-based risk assessment system not only aids in predicting patient prognosis but also guides the identification of populations suitable for combined treatment. Molecules represented by HTR2B in the model may serve as effective therapeutic targets for UVM.Communicated by Ramaswamy H. Sarma.
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Purpose: To investigate the etiology and demographic associations of patients presenting with eyelid lacerations to a US level 1 trauma center emergency department (ED). Patient and Methods: A retrospective chart review of all patients with eyelid lacerations presenting to the ED at a single level 1 trauma center was performed. Eyelid lacerations were categorized as simple eyelid lacerations, eyelid lacerations with eyelid margin involvement, and eyelid lacerations with nasolacrimal system involvement. Data on demographics and clinical characteristics were analyzed. Results: A total of 303 eyelid laceration cases were identified, 56% were simple eyelid lacerations, followed by 24% with nasolacrimal involvement and 20% involving the eyelid margin. Sixty percent of animal bites/scratches resulted in a nasolacrimal system involving laceration, most commonly affecting children. Falls were the most common etiology in children and patients over the age of 60. Black patients, patients presenting with concomitant ophthalmic injuries, and those with Medicaid insurance were more likely to have an assault etiology (p < 0.05 for all). Conclusion: Falls were the most common etiology for eyelid lacerations in children and the elderly, while assault was the most common in adults. Identifying the most common etiology by demographic factors can help raise awareness regarding targeted prevention strategies for high-risk populations.
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Hydrophones play a crucial role in underwater target detection within sonar systems. However, existing hydrophones often encounter challenges such as low sensitivity and poor signal-to-noise ratio (SNR) in the detection of low-frequency acoustic signals. This work introduces a capacitive hydrophone (CH) designed for highly sensitive detection of low-frequency underwater sound signals. Comprising a latex film/silver electrode and a structured hydrogel as the electrolyte layer, the CH is enclosed in a cylindrical casing. By strategically integrating a carbon nanotube (CNT) topology network within a pyramid microarray in the hydrogel, the sensor efficiently forms the electric double layer (EDL), enhancing sensitivity and precision. The CH showcases exceptional low-pressure sensitivity across a wide frequency spectrum (20 to 800 Hz), achieving a receiving sensitivity of up to -159.7 dB in the critical low-frequency band (20 to 125 Hz), surpassing the performance of the commercial hydrophone (RHC-14) by a substantial margin of 33.29 dB. Furthermore, the CH maintains a superior SNR, enabling the detection of sound waves as faint as 0.3 Pa. This study demonstrates the capabilities of the CH in detecting maritime vessels and underwater sounds, underscoring the potential of the CNT-enhanced EDL sensing mechanism for future low-frequency hydrophone design.
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Purpose: To evaluate choroidal thickness and retinal nerve fiber layer (RNFL) thickness in different trimesters using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods: A prospective comparative study included 45 healthy pregnant women in the first trimester, 45 women in the second, 45 women in the third and 45 healthy non-pregnant women as the control group. Macular choroidal thickness was measured at three locations: The subfoveal, 1 âmm temporal, and 1 âmm nasal from the fovea with EDI-OCT. Peripapillary choroidal thickness (PPCT) and RNFL thickness parameters were automatically calculated by the Spectralis OCT. Results: The subfoveal, temporal and nasal macular choroidal thickness were all significantly thicker in the second trimester, compared with those parameters in the first, the third trimesters and the control group (all P â< â0.05). The PPCT was significantly increased in the second trimeter compared with the control group at global, temporal, temporal inferior, nasal and nasal inferior positions (all P â< â0.05). The RNFL thickness was also significantly increased in pregnant women at nasal superior and nasal inferior quadrants (all P â< â0.05). Conclusions: The choroidal thickness in pregnant women was found to be thicker than the control group, regardless of macular or optic disc location. Findings of RNFL thickening might indicate subclinical involvement of the central nervous system.