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Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.
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Herein, the micro-porous polylactic acid coating applied on the surface of the cylindrical substrate is fabricated by a novel in situ pore-formation strategy based on the combinational effect of breath figure (BF) and vapor-induced phase separation (VIPS) processes. Under the condition of high environmental humidity, solvent pair of chloroform and dimethylformamide is employed for post-treatment onto pre-formed PLA coating to induce the pore-formation following the mechanism of BF and VIPS, respectively. A composite porous structure with both cellular-like and bi-continuous network morphologies is obtained. By tunning the experimental factors including the ratio of the solvent pair, environmental humidity, and temperature, morphological manipulation upon the pore morphology can be facilely achieved based on the control of mechanism transition between BF and VIPS. Paclitaxel is used as a model drug and loaded into the porous coating by the wicking effect of post-immersion. Coatings with different morphological features show varying drug loading and release capacities. The 28-day release test reveals dynamic release profiles between different coating samples, with the total release rate ranging from 35.70% to 79.96%. Optimal loading capacity of 19.28 µg cm-2 and 28-day release rate of 35.70% are achieved for the coating with composite BF-VIPS structure. This research established a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of drug-eluting coating with the feature of manipulative drug delivery.
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This study employed segmented variable-frequency ultrasound synergistic hot-air drying (SVFU-HAD) for Rhubarb slices, selected two sets of time nodes for frequency conversion (60 min, 120 min, and 90 min, 150 min), and two sequences of frequency conversion (high-frequency to low-frequency, and low-frequency to high-frequency). It aimed to investigate the effects of SVFU-HAD on the drying characteristics, quality, and heat transfer of Rhubarb slices. The findings indicated that segmented variable-frequency ultrasound has advantages in increasing drying rate and improving uniformity of cavitation effects compared to constant-frequency ultrasound. Analysis of physical properties revealed that the rehydration performance of dried products subjected to ultrasonic variable-frequency treatment (90 min, 150 min) according to the drying rate was better (RR > 3.3). The transition mode from high-frequency to low-frequency in variable-frequency ultrasonic treatment contributes to maintaining the overall color of Rhubarb. Analysis of chemical properties unveiled that Rhubarb treated with 40 kHz (0 min)-28 kHz (60 min)-25 kHz (120 min) segmented variable-frequency ultrasound contained overall higher levels of tannins, dianthrones and free anthraquinones content, which exceeded the average values by 3.24%, 26.65%, and 14.42%, respectively. In addition, thermal analysis results based on ANSYS Workbench software demonstrated that the drying uniformity of SVFU-HAD is superior to that of hot-air drying and constant-frequency ultrasound synergistic hot-air drying (CFU-HAD). Overall, the SVFU-HAD method employed in this study presents an innovative approach to ultrasound synergistic hot-air drying research with promising potential for enhancing the efficiency and quality characteristics of Rhubarb slices.
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Desecación , Calor , Rheum , Rheum/química , Desecación/métodos , Aire , Ondas UltrasónicasRESUMEN
To achieve rapid preparation of hydrogels without using conventional chemical initiators, a stable suspension of eutectic gallium indium (EGaIn) liquid metal nanoparticles is explored by probe-sonicating the metal in an aqueous solution. Liquid metal suspension was sonicated to serve as a photo-initiator for acrylamide polymerization and produce hydrogels. The initiation effect comes from the fact that liquid metal suspension after sonication can produce a large number of free radicals when exposed to ultraviolet (UV) radiation, leading to initiation. The changes of liquid metal nanodroplets under UV light irradiation have been systematically investigated. Further, the liquid metal colloidal solutions were used to prepare hydrogels with the same transparency and adjustable mechanical properties as the samples initiated by commercial photo-initiators. This work shows the great application potential of liquid metal in the preparation of hydrogels and provides a new technical idea for the design of multifunctional hydrogels.
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Enhancing the flame retardancy of epoxy (EP) resins typically entailed a trade-off with other physical properties. Herein, hyperbranched poly(amidoamine) (HPAA) and phytic acid (PA) were used to functionalize graphene oxide (GO) via electrostatic self-assembly in water to prepare a phosphorus-nitrogen functionalized graphene oxide nanosheet (PN-GOs), which could be utilized as high efficient flame-retardant additive of epoxy resin without sacrificing other properties. The PN-GOs demonstrated improved dispersion and compatibility within the EP matrix, which resulted in significant concurrent enhancements in both the mechanical performance and flame-retardant properties of the PN-GOs/EP nanocomposites over virgin EP. Notably, the incorporation of just 1.0 wt% PN-GOs yielded a 20.4, 6.4 and 42.7 % increases in flexural strength, flexural modulus and impact strength for the PN-GOs/EP nanocomposites, respectively. Furthermore, simultaneous reductions were achieved in the peak heat release rate (pHRR) by 60.0 %, total smoke production (TSP) by 43.0 %, peak CO production rate (pCOP) by 57.9 %, and peak CO2 production rate (pCO2P) by 63.9 %. This study presented a facile method for the design of GO-based nano flame retardants, expanding their application potential in polymer-matrix composites.
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Human cytomegalovirus (HCMV), a widely prevalent human beta-herpesvirus, establishes lifelong persistence in the host following primary infection. In healthy individuals, the virus is effectively controlled by HCMV-specific T cells and typically exhibits asymptomatic. The T cell immune response plays a pivotal role in combating HCMV infection, while HCMV employs various strategies to counteract it within the host. Previously, we reported that UL23, a tegument protein of HCMV, facilitates viral immune evasion from interferon-gamma (IFN-γ) responses, and it is well known that IFN-γ is mainly derived from T cells. However, the involvement of UL23 in viral immune evasion from T cell-mediated immunity remains unclear. Herein, we present compelling evidence that UL23 significantly enhances viral resistance against T cell-mediated cytotoxicity during HCMV infection from the co-culture assays of HCMV-infected cells with T cells. We found that IFN-γ plays a major role in regulating T cell cytotoxicity mediated by UL23. More interestingly, we demonstrated that UL23 not only regulates the IFN-γ downstream responses but also modulates the IFN-γ secretion by regulating T cell activities. Further experiments indicate that UL23 upregulates the expression and signaling of programmed death ligand 1 (PD-L1), which is responsible for inhibiting multiple aspects of T cell activities, including activation, apoptosis, and IFN-γ secretion, as determined through RNA-seq analysis and inhibitor-blocking experiments, ultimately facilitating viral replication and spread. Our findings highlight the potential role of UL23 as an alternative antagonist in suppressing T cell cytotoxicity and unveil a novel strategy for HCMV to evade T cell immunity. IMPORTANCE: T cell immunity is pivotal in controlling primary human cytomegalovirus (HCMV) infection, restricting periodic reactivation, and preventing HCMV-associated diseases. Despite inducing a robust T cell immune response, HCMV has developed sophisticated immune evasion mechanisms that specifically target T cell responses. Although numerous studies have been conducted on HCMV-specific T cells, the primary focus has been on the impact of HCMV on T cell recognition via major histocompatibility complex molecules. Our studies show for the first time that HCMV exploits the programmed death ligand 1 (PD-L1) inhibitory signaling pathway to evade T cell immunity by modulating the activities of T cells and thereby blocking the secretion of IFN-γ, which is directly mediated by HCMV-encoded tegument protein UL23. While PD-L1 has been extensively studied in the context of tumors and viruses, its involvement in HCMV infection and viral immune evasion is rarely reported. We observed an upregulation of PD-L1 in normal cells during HCMV infection and provided strong evidence supporting its critical role in UL23-induced inhibition of T cell-mediated cytotoxicity. The novel strategy employed by HCMV to manipulate the inhibitory signaling pathway of T cell immune activation for viral evasion through its encoded protein offers valuable insights for the understanding of HCMV-mediated T cell immunomodulation and developing innovative antiviral treatment strategies.
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Antígeno B7-H1 , Infecciones por Citomegalovirus , Citomegalovirus , Evasión Inmune , Interferón gamma , Transducción de Señal , Humanos , Citomegalovirus/inmunología , Citomegalovirus/fisiología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Linfocitos T/inmunología , Linfocitos T/virología , Proteínas Virales/metabolismo , Proteínas Virales/inmunología , Proteínas Virales/genéticaRESUMEN
Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG-Mngel) formed by crosslinking sodium alginate (SA) with manganese-doped bioactive glass (BG-Mn) is developed as a versatile platform for anti-tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune-suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG-Mngel with anti-PD-1 antibody (α-PD-1) for the treatment of malignant melanoma, it shows enhanced anti-tumor immune response and long-term immune memory response. Remarkably, BG-Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.
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Hidrogeles , Melanoma , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Melanoma/terapia , Melanoma/patología , Modelos Animales de Enfermedad , Hipertermia Inducida/métodos , Humanos , Metástasis de la Neoplasia , Línea Celular Tumoral , Rayos Infrarrojos/uso terapéuticoRESUMEN
BACKGROUND & AIMS: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including hepatitis B surface antigen, hepatitis B envelope antigen, hepatitis B core antigen, HBV DNA, and HBV RNA. RESULTS: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. CONCLUSION: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.
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Rapid and quantitative detection of 2,4,6-trinitrophenol (TNP) is very crucial for homeland security, military application, and environment protection. Herein, a nine-metal Zn(II)-Nd(III) nanoring 1 with a diameter of 2.3 nm was constructed by the use of a long-chain Schiff base ligand, which shows ratiometric fluorescence response to TNP with high selectivity and sensitivity. The fluorescence sensing behavior of 1 to TNP is expressed by a first-order equation I1060nm/I560nm = -0.0128*[TNP] + 0.9723, which can be used to quantitatively analyze TNP concentrations in solution. The limits of detection (LODs) to TNP based on the ligand-centered (LC) and Nd(III) emissions of 1 are 5.93 µM and 3.18 µM, respectively. The fluorescence response mechanism to TNP is attributed to the competitive absorption effect and photoinduced electron transfer (PET). The luminescence quenching of 1 is dominated by static process.
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Rapid and quantitative detection of isoquercitrin (Isq) has been attracting much attention due to its outstanding pharmacological and physiological activities. Herein, an interesting 48-metal Zn(II)-Nd(III) nanocluster (1, molecular sizes 1.3 × 2.8 × 3.1 nm) with salen-type Schiff base ligand was constructed as molecular sensor for the luminescence detection of Isq. 1 exhibits visible ligand-centered emission and NIR luminescence of Nd(III), and shows ratiometric fluorescence response to Isq with high sensitivity even in the presence of other interferences. The fluorescence sensing behavior can be expressed by a second-order equation I1060nm/I480nm = A*[Isq]2 + B*[Isq] + C, which is used to quantitatively analyze the Isq concentrations in DMF and FCS. The LODs to Isq for the ligand-centered and lanthanide emissions of 1 in DMF are 0.21 µM and 0.11 nM, respectively. The quenching of the ligand-centered emission of 1 caused by Isq is attributed to the competitive absorption of light energy and "inner effect", while, the luminescence enhancement is due to the "antenna effect".
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Introduction: Accurate detection of potato seedlings is crucial for obtaining information on potato seedlings and ultimately increasing potato yield. This study aims to enhance the detection of potato seedlings in drone-captured images through a novel lightweight model. Methods: We established a dataset of drone-captured images of potato seedlings and proposed the VBGS-YOLOv8n model, an improved version of YOLOv8n. This model employs a lighter VanillaNet as the backbone network in-stead of the original YOLOv8n model. To address the small target features of potato seedlings, we introduced a weighted bidirectional feature pyramid network to replace the path aggregation network, reducing information loss between network layers, facilitating rapid multi-scale feature fusion, and enhancing detection performance. Additionally, we incorporated GSConv and Slim-neck designs at the Neck section to balance accuracy while reducing model complexity. Results: The VBGS-YOLOv8n model, with 1,524,943 parameters and 4.2 billion FLOPs, achieves a precision of 97.1%, a mean average precision of 98.4%, and an inference time of 2.0ms. Comparative tests reveal that VBGS-YOLOv8n strikes a balance between detection accuracy, speed, and model efficiency compared to YOLOv8 and other mainstream networks. Specifically, compared to YOLOv8, the model parameters and FLOPs are reduced by 51.7% and 52.8% respectively, while precision and a mean average precision are improved by 1.4% and 0.8% respectively, and the inference time is reduced by 31.0%. Discussion: Comparative tests with mainstream models, including YOLOv7, YOLOv5, RetinaNet, and QueryDet, demonstrate that VBGS-YOLOv8n outperforms these models in terms of detection accuracy, speed, and efficiency. The research highlights the effectiveness of VBGS-YOLOv8n in the efficient detection of potato seedlings in drone remote sensing images, providing a valuable reference for subsequent identification and deployment on mobile devices.
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Meloxicam (MLX) is a novel nonsteroidal anti-inflammatory drug, but on the other hand, it has become one of the common microcontaminants in surface waters and sewage. Herein, we report the preparation of a ternary-metal Zn(II)-Cd(II)-Eu(III) nanocluster 1 for the response of MLX through the enhancement of lanthanide luminescence. The luminescence sensing behavior of 1 is expressed by the equation I615nm = 3060 × [MLX] + 46,604, which can be used in the quantitative analysis of MLX concentrations in meloxicam dispersible tablets. Filter paper strips bearing 1 can be used to qualitatively detect MLX by a color change to red under a UV lamp. The luminescence response time is no more than five s, and the detection limit is as low as 2.31 × 10-2 nM.
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Antiinflamatorios no Esteroideos , Europio , Meloxicam , Zinc , Meloxicam/análisis , Zinc/química , Zinc/análisis , Europio/química , Antiinflamatorios no Esteroideos/análisis , Antiinflamatorios no Esteroideos/química , Mediciones Luminiscentes , Luminiscencia , Nanoestructuras/química , Límite de DetecciónRESUMEN
Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.
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A nine-metal Zn(II)-Eu(III) nanoring 1 with a diameter of about 2.3 nm was constructed by the use of a long-chain Schiff base ligand. It shows a luminescence response to neopterin (Neo) through the enhancement of lanthanide emission with high selectivity and sensitivity, which can be used to quantitatively analyze the concentrations of Neo in fetal calf serum and urine. The luminescence sensing of 1 to Neo is temperature-dependent, and it displays more obvious response behavior at lower temperatures. Filter paper strips bearing 1 can be used to qualitatively detect Neo by the color change from chartreuse to red under a UV lamp. The limit of detection is as low as 3.77 × 10-2 nM.
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Europio , Nanoestructuras , Neopterin , Temperatura , Zinc , Zinc/química , Zinc/análisis , Neopterin/análisis , Neopterin/orina , Neopterin/sangre , Europio/química , Nanoestructuras/química , Humanos , Luminiscencia , Mediciones Luminiscentes , Biomarcadores/análisis , Biomarcadores/sangre , Límite de Detección , AnimalesRESUMEN
A cube-like Zn(II)-Eu(III) nanocluster 1 (molecular sizes: 1.8 × 2.0 × 2.0 nm) was constructed by the use of a new long-chain Schiff base ligand. It shows a ratiometric fluorescence response to levofloxacin (LFX) with high sensitivity and selectivity, which can be expressed as I615 nm/I550 nm = A*[LFX]2 + B*[LFX] + C. It is used to quantitatively detect the LFX concentrations in fetal calf serum (FCS) and tablets sold in pharmacy. Filter paper strips bearing 1 can be used to qualitatively detect LFX by a color change to red under a UV lamp. 1 and its hybrid with sodium alginate (SA), 1@SA, display potential applications in the qualitative detection of LFX in FCS and the medicine. The limit of detection of 1 to LFX is as low as 2.1 × 10-2 nM.
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Alginatos , Europio , Levofloxacino , Zinc , Alginatos/química , Zinc/química , Zinc/sangre , Levofloxacino/sangre , Levofloxacino/análisis , Europio/química , Espectrometría de Fluorescencia , Animales , Humanos , Bovinos , Comprimidos , Colorantes Fluorescentes/químicaRESUMEN
Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques. We then perform loss-of-function screens to identify the nuclear export gene, XPO1, as a vulnerability. We find that the FDA approved XPO1 inhibitor, KPT-330, suppresses TRIP13 expression, which is required for survival. We further identify synergy between KPT-330 and doxorubicin, a chemotherapy used in high-risk FHWT. Taken together, we identify XPO1 inhibition with KPT-330 as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.
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Hidrazinas , Neoplasias Renales , Triazoles , Tumor de Wilms , Humanos , Proteína Exportina 1 , Transporte Activo de Núcleo Celular , Carioferinas/genética , Carioferinas/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Línea Celular Tumoral , Apoptosis , Recurrencia Local de Neoplasia , Doxorrubicina/farmacología , Tumor de Wilms/tratamiento farmacológico , Tumor de Wilms/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMEN
The epidermal growth factor receptor, EGFR, is frequently activated in lung cancer and glioblastoma by genomic alterations including missense mutations. The different mutation spectra in these diseases are reflected in divergent responses to EGFR inhibition: significant patient benefit in lung cancer, but limited in glioblastoma. Here, we report a comprehensive mutational analysis of EGFR function. We perform saturation mutagenesis of EGFR and assess function of ~22,500 variants in a human EGFR-dependent lung cancer cell line. This approach reveals enrichment of erlotinib-insensitive variants of known and unknown significance in the dimerization, transmembrane, and kinase domains. Multiple EGFR extracellular domain variants, not associated with approved targeted therapies, are sensitive to afatinib and dacomitinib in vitro. Two glioblastoma patients with somatic EGFR G598V dimerization domain mutations show responses to dacomitinib treatment followed by within-pathway resistance mutation in one case. In summary, this comprehensive screen expands the landscape of functional EGFR variants and suggests broader clinical investigation of EGFR inhibition for cancers harboring extracellular domain mutations.
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Glioblastoma , Neoplasias Pulmonares , Humanos , Glioblastoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , MutaciónRESUMEN
OBJECTIVE: To construct and evaluate a nomogram prediction model for the risk of diabetic foot in patients with type 2 diabetes based on their clinical data, and to assist clinical healthcare professionals in identifying high-risk factors and developing targeted intervention measures. METHODS: We retrospectively collected clinical data from 478 hospitalized patients with type 2 diabetes at the First Affiliated Hospital of Shantou University Medical College from January 2019 to December 2021. The patients were divided into a diabetic foot group (n=312) and a non-diabetic foot group (n=166) based on whether they had diabetic foot. The baseline data of both groups were collected. Univariate and multivariate analyses as well as logistic regression analysis were conducted to explore the risk factors for diabetic foot. A nomogram prediction model was established using the package "rms" version 4.3. The model was internally validated using the area under the receiver operating characteristic curve (AUC). Additionally, the decision curve analysis (DCA) was performed to evaluate the performance of the nomogram model. RESULTS: The results from the logistic regression analysis revealed that being male, smoking, duration of diabetes, glycated hemoglobin, hyperlipidemia, and atherosclerosis were influencing factors for diabetic foot (all P<0.05). The AUC of the model in predicting diabetic foot was 0.804, with a sensitivity of 75.3% and specificity of 74.4%. Harrell's C-index of the nomogram prediction model for diabetic foot was 0.804 (95% CI: 0.762-0.844), with a threshold value of >0.675. The DCA findings demonstrated that the nomogram model provided a net clinical benefit. CONCLUSION: The nomogram prediction model constructed in this study showed good predictive performance and can provide a basis for clinical workers to prevent and intervene in diabetic foot, thereby improving the overall diagnosis and treatment.
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The active cyano-group in polyacrylonitrile has severe passivation of lithium anode under larger current density, which restricts the wide application of polyacrylonitrile(PAN) in lithium metal batteries. Herein, in order to address the excessive passivation of lithium metal by PAN, inspired by the pre-oxidation of carbon fibers, PAN was pre-oxidized at 230 °C, which transformed part of the cyano group into a more chemically stable cyclized structure. The electrochemical and mechanical properties of the composite solid electrolyte were effectively improved by introducing the fast ionic conductor Li6.25La3Zr2Al0.25O12 into PAN by electrospinning. The oxidized PAN-based composite solid electrolyte presents high ionic conductivity (3.05 × 10-3 S·cm-1) and high lithium transference number of 0.79 at 25 °C, further contributing to a high electrochemical window (5.3 V). The solid-state batteries assembled by Li||10 wt%-LLZAO@230-oxy-PAN||NCM523 behave superb electrochemical performance, delivering a high initial discharge capacity of 157 mAh g-1 at 0.2 C. After 100 cycles, the capacity retention was 93.3 %, indicating the electrolyte displays great electrochemical stability. This work provides new insights into the structural design of polymer-based high-voltage batteries.