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COVID-19 , Neoplasias Hematológicas , Reinfección , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/virología , Factores de Riesgo , Masculino , Persona de Mediana Edad , Reinfección/epidemiología , Reinfección/virología , Femenino , Anciano , Adulto , Índice de Severidad de la EnfermedadRESUMEN
An in-depth understanding of structure-activity relationship between the phase constitution and solar-to-hydrogen (STH) conversion efficiency is conducive to guiding the optimization route of targeted photocatalyst candidates, further establishing advanced photocatalytic systems. Herein, based on the concept of phase engineering, we encompassed the crystalline phase of CdS and achieved precise regulation of phase proportion as well as phase boundary width in the phase junction for the first time. The above cooperative effect not only modifies energy band distribution for sufficient redox potentials, but also guarantees the reverse migration orientation of photogenerated carriers in phase junction, thereby endowing photocarriers with a prolonged lifetime. Compared to pure cubic or hexagonal phase (72.6 or 101.1 µmol h-1 g-1), this CdS system with optimized phase junction demonstrates an improved photocatalytic hydrogen evolution activity of 1.04 mmol h-1 g-1 and favorable stability without cocatalyst assistance, which mainly stems from an efficient protons reduction process interacting with long-lived photogenerated electrons. This research explores the mechanism behind phase regulation and its relationship with junction capability, providing a powerful strategy to manipulate crystal phase distribution and paving a feasible avenue for other phase-dependent photocatalysts towards rational design of heterostructures based on different phases in solar energy conversion field.
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Transition-metal species embedded in carbon have sparked intense interest in the fields of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, improvement of the electrocatalytic kinetics remains a challenge caused by the synergistic assembly. Here, we propose a biochemical strategy to fabricate the Co nanoparticles (NPs) and Co/Ni-N4-C co-embedded N-doped porous carbon (CoNPs&Co/Ni-N4-C@NC) catalysts via constructing the zeolitic imidazolate framework (ZIF)@yeast precursor. The rich amino groups provide the possibility for the anchorage of Co2+/Ni2+ ions as well as the construction of Co/Ni-ZIF@yeast through the yeast cell biomineralization effect. The functional design induces the formation of CoNPs and Co/Ni-N4-C sites in N-doped carbon as well as regulates the porosity for exposing such sites. Synergy of CoNPs, Co/Ni-N4-C, and porous N-doped carbon delivered excellent electrocatalytic kinetics (the ORR Tafel slope of 76.3 mV dec-1 and the OER Tafel slope of 80.4 mV dec-1) and a high voltage of 1.15 V at 10 mA cm-2 for the discharge process in zinc air batteries. It provides an effective strategy to fabricate high-performance catalysts.
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BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.
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Carcinoma Pulmonar de Lewis , Macrófagos , Animales , Ratones , Carcinoma Pulmonar de Lewis/radioterapia , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Indazoles/farmacología , Macrófagos/metabolismo , Propionatos/farmacología , Análisis de Secuencia de ARN , Microambiente Tumoral/genética , Análisis de la Célula Individual , Quimiocina CCL8RESUMEN
PURPOSE/OBJECTIVE(S): To establish the distribution pattern of cervical lymph node metastasis (LNM) and propose optimized clinical target volume (CTV) boundaries specific to oral/ oropharyngeal squamous cell cancer (OSCC/OPSCC). MATERIALS/METHODS: 531 patients with pathologically confirmed OSCC/OPSCC were enrolled from January 2013 to June 2022. Patients were stratified into two groups based on the minimal distance from the lesion's edge to the body's midline: ≤1 cm or > 1 cm. The geometric center of cervical metastatic LN was marked on a template CT. LN distribution probability maps were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for CTV boundaries specific to OSCC/OPSCC. RESULTS: A total of 1962 positive LNs were enrolled. Compared with the > 1 cm group, the ≤ 1 cm group has following feature tendencies: male smokers, younger, median organs, large gross lesion, infiltrative growth pattern, contralateral LNM. The most frequently involved level of LNM was ipsilateral II, but ipsilateral Ib had the highest involvement rate in the > 1 cm OSCC group. In addition, tongue cancer had a higher incidence of LN extranodal extension (ENE), which mainly distributes in ipsilateral level II. The skip metastasis was prone to from level III to Vb (3.5 %) in LN(+)/ENE (-), and level Ib to VIa (3.7 %) in LN(+)/ENE (+). Accordingly, we proposed the following modifications: 1. only including lateral and posterior margin of submandibular gland within 5 mm; 2. retracting posterior boundary of level II to front edge of levator scapula muscle, and descending the upper boundary to transverse process of C2 vertebra only for OSCC; 3. including posterior third of thyroglossal muscle or anterior edge of sternocleidomastoid muscle; 4. sparing level Va in case of only level II involvement; 5. including upper area of the thyroid cartilage plate in case of level Ib LN(+)/ENE (+); 6. sparing level VIIa is considered. CONCLUSION: This is the first description of LN topographic spread patterns for OSCC/OPSCC. Modified CTV for prophylactic irradiation was proposed to spare the organs at risk and minimize adverse effects.
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Metástasis Linfática , Neoplasias de la Boca , Neoplasias Orofaríngeas , Humanos , Masculino , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/patología , Femenino , Persona de Mediana Edad , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/patología , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de la radiación , Adulto , Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Planificación de la Radioterapia Asistida por Computador/métodos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Anciano de 80 o más AñosRESUMEN
Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.
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Linfocitos T CD8-positivos , Células Asesinas Naturales , Neoplasias Pulmonares , Ratones Endogámicos C57BL , Microambiente Tumoral , Animales , Células Asesinas Naturales/inmunología , Microambiente Tumoral/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Linfocitos T CD8-positivos/inmunología , Ratones , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Melanoma Experimental/terapia , Linfocitos Infiltrantes de Tumor/inmunología , Fenotipo , Receptor de Muerte Celular Programada 1 , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacologíaRESUMEN
OBJECTIVES: To investigate the feasibility of T1rho-weighted imaging in differentiating malignant from benign breast lesions and to explore the additional value of T1rho to conventional MRI. MATERIALS AND METHODS: We prospectively enrolled consecutive women with breast lesions who underwent preoperative T1rho-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) between November 2021 and July 2023. The T1rho, apparent diffusion coefficient (ADC), and semi-quantitative parameters from DCE-MRI were obtained and compared between benign and malignant groups. The diagnostic performance was analyzed and compared using receiver operating characteristic (ROC) curves and the Delong Test. RESULTS: This study included 113 patients (74 malignant and 39 benign lesions). The mean T1rho value in the benign group (92.61 ± 22.10 ms) was significantly higher than that in the malignant group (72.18 ± 16.37 ms) (P < 0.001). The ADC value and time to peak (TTP) value in the malignant group (1.13 ± 0.45 and 269.06 ± 106.01, respectively) were lower than those in the benign group (1.57 ± 0.45 and 388.30 ± 81.13, respectively) (all P < 0.001). T1rho combined with ADC and TTP showed good diagnostic performance with an area under the curve (AUC) of 0.896, a sensitivity of 81.0%, and a specificity of 87.1%. The specificity and sensitivity of the combination of T1rho, ADC, and TTP were significantly higher than those of the combination of ADC and TTP (87.1% vs. 84.6%, P < 0.005; 81.0% vs. 77.0%, P < 0.001). CONCLUSION: T1rho-weighted imaging was a feasible MRI sequence for differentiating malignant from benign breast lesions. The combination of T1rho, ADC and TTP could achieve a favorable diagnostic performance with improved specificity and sensitivity, T1rho could serve as a supplementary approach to conventional MRI.
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Neoplasias de la Mama , Imagen por Resonancia Magnética , Humanos , Femenino , Sensibilidad y Especificidad , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Curva ROC , Diagnóstico Diferencial , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Mama/diagnóstico por imagen , Mama/patología , Medios de Contraste/farmacologíaRESUMEN
Twins in crystal defect, one of the significant factors affecting the physicochemical properties of semiconductor materials, are applied in catalytic conversion. Among the catalysts serving for photocatalytic water splitting, Zn1- x Cdx S has become a hot-point due to its adjustable energy band structure. Via limiting mass transport to control the release rate of anions/cations, twin Zn1- x Cdx S solid solution is prepared successfully, which lays a foundation for the construction of other twin crystals in the future. On twin Zn1- x Cdx S, water tends to be dissociated after being adsorbed by Zn2+ /Cd2+ at twin boundary, then the fast-moving electrons at twin boundary quickly combine with the protons already attached to S2- to form hydrogen. According to the theoretical calculation, not only the intracrystalline electron mobility, but also the extracrystalline capacity of water-adsorption/dissociation and proton-adsorption on the twin boundary are superior to those of the counterpart plane in defect-free phase. The synthetic twin Zn1- x Cdx S apparent quantum efficiency of photocatalysis water splitting for hydrogen reached 82.5% (λ = 420 nm). This research opens up an avenue to introduce twins in crystals and it hopes to shed some light on photocatalysis.
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Carbon dots (CDs) are a newly discovered type of fluorescent material that has gained significant attention due to their exceptional optical properties, biocompatibility, and other remarkable characteristics. However, single CDs have some drawbacks such as self-quenching, low quantum yield (QY), and poor stability. To address these issues, researchers have turned to organosilicon, which is known for its green, economical, and abundant properties. Organosilicon is widely used in various fields including optics, electronics, and biology. By utilizing organosilicon as a synthetic precursor, the biocompatibility, QY, and resistance to self-quenching of CDs can be improved. Meanwhile, the combination of organosilicon with CDs enables the functionalization of CDs, which significantly expands their original application scenarios. This paper comprehensively analyzes organosilicon in two main categories: precursors for CD synthesis and matrix materials for compounding with CDs. The role of organosilicon in these categories is thoroughly reviewed. In addition, the paper presents various applications of organosilicon compounded CDs, including detection and sensing, anti-counterfeiting, optoelectronic applications, and biological applications. Finally, the paper briefly discusses current development challenges and future directions in the field.
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Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.
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COVID-19 , Neoplasias Hematológicas , Humanos , Formación de Anticuerpos , SARS-CoV-2 , Estudios Prospectivos , Neoplasias Hematológicas/complicaciones , Progresión de la Enfermedad , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
Callicarpa nudiflora (C. nudiflora) is widely used in the treatment of bleeding related diseases. However, its main material basis has not been fully defined which limits the in-depth study of screening out the material basis of hemostasis and coagulation from C. nudiflor. In this study, the method of spectrum-effect relationship was used to quickly screen the material basis of hemostasis and coagulation. The five compounds related to hemostasis and coagulation were screened as Alyssonoside (P24), Luteolin (P25), Quercetin (P26), Apigenin (P28), Isorhamnetin (P29). And the contribution of these five peaks to hemostasis and coagulation efficacy was P24 > P25 > P28 > P26 > P29.
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Photothermal materials that can convert solar energy into heat energy through photothermal conversion have attracted extensive attention, but these materials are easily polluted by the environment. Here, we propose a simple and effective strategy for constructing photothermal superhydrophobic cotton fabrics with self-cleaning ability. The PDA@PEI@GA@Ag@PDMS-coated cotton fabric can achieve good superhydrophobicity (water contact angle: 159.6°) by a simple dipping method and mussel-inspired dopamine surface modification, which is regulated by the mass of dopamine, the mass of silver nitrate, and the concentration of polydimethylsiloxane (PDMS). The coated cotton fabric has good physical and chemical stability. Meanwhile, the coated cotton fabric has excellent self-cleaning and antifouling properties. The superhydrophobic PDA@PEI@GA@Ag@PDMS fabric exhibits excellent and stable photothermal properties, with the surface temperature reaching 70.4 °C under simulated sunlight with a current of 20 A. This photothermal superhydrophobic fabric with self-cleaning properties is expected to be applied in the field of photothermal conversion.
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Purpose: Brain metastases (BMs) are common in Small Cell Lung Cancer (SCLC), but the prognosis is very poor. Currently, there is no standard of care on what constitutes optimal treatment, and there is no consensus regarding maintenance therapy in SCLC. Case description: We report the case of a 55-year-old man with advanced SCLC. After the initial diagnosis, he received routine chemotherapy and chest radiotherapy but developed brain metastases with 2 lesions seven months later. We used an effective combination therapy consisting of the antiangiogenic inhibitor, Anlotinib and whole-brain radiotherapy. We then administered anti-PD-L1 immunotherapy Atezolizumab in combination with Anlotinib as long-term maintenance therapy. Twelve months later, there was a progression in one of the brain metastases. The patient underwent further stereotactic radiotherapy (SRT) for the lesion. However, after four months of treatment with SRT, the lesion began to gradually grow in size. The patient underwent surgical resection of the lesion, which confirmed radioactive brain necrosis. After a full 3-year course of anti-PD-L1 therapy, the patient discontinued immunotherapy and was administered only Anlotinib as maintenance. At the time of writing up this report, the patient was alive and the overall survival reached 41 months after the onset of BM. Conclusion: This indicated a potential synergistic effect of combined immunotherapy and antiangiogenic targeted therapy with local radiotherapy in patients with BM-SCLC and can provide directions for future clinical decisions.
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Objective: Patellofemoral grind refers to the tender behind the knee cap while contracting the quadriceps muscle during the patellar grind test. The present investigation aims to elucidate the association between patellofemoral grind and synovitis in the knee osteoarthritis (KOA). Method: A total of 1,119 knees with complete patellofemoral grind and synovitis assessment records from the Osteoarthritis Initiative (OAI) were investigated in this study. The Magnetic Resonance Imaging at baseline, 12 months, and 24 months of follow-up were employed to evaluate synovitis. Frequent patellofemoral grind was operationally defined as occurring more than twice at three different time points. In addition, a sensitivity stratification was conducted to examine gender differences. Results: The study participants had an average age of 61 years, with 62.4% being female. The findings revealed that baseline patellofemoral grind was significantly associated with changes in synovitis at follow-up (odds ratio [OR]: 1.44, confidence interval [CI]: 1.04-1.98) and was also linked to synovitis worsening over 24 months (OR: 1.67, CI: 1.13-2.46) in all subjects. For the subjects with frequent patellofemoral grind, this correlation was more significant (OR: 1.50, CI: 1.03-2.16; OR: 1.71, CI: 1.09-2.67). In the context of sensitivity stratification, it was observed that the baseline and frequent patellofemoral grind in females exhibited a significant correlation with synovitis. However, no significant correlation was found in males. Conclusion: Patellofemoral grind may serve as a potential risk factor of synovitis in knee osteoarthritis, particularly among female patients, and thus, necessitates close monitoring and management by clinical physicians.
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BACKGROUND: The prognostic significance of non-cancer-related prognostic factors, such as body composition, has gained extensive attention in oncological research. Compared with sarcopenia, the prognostic significance of adipose tissue for overall survival in non-small cell lung cancer remains unclear. We investigated the prognostic value of skeletal muscle and adipose tissue in patients with non-small cell lung cancer. METHODS: This retrospective study included 4434 patients diagnosed with non-small cell lung cancer between January 2014 and December 2016. Cross-sectional areas of skeletal muscle and subcutaneous fat were measured, and the pericardial fat volume was automatically calculated. The skeletal muscle index and subcutaneous fat index were calculated as skeletal muscle area and subcutaneous fat area divided by height squared, respectively, and the pericardial fat index was calculated as pericardial fat volume divided by body surface area. The association between body composition and outcomes was evaluated using Cox proportional hazards model. RESULTS: A total of 750 patients (501 males [66.8%] and 249 females [33.2%]; mean age, 60.9 ± 9.8 years) were included. Sarcopenia (60.8% vs. 52.7%; P < 0.001), decreased subcutaneous fat index (51.4% vs. 25.2%; P < 0.001) and decreased pericardial fat index (55.4% vs. 16.5%; P < 0.001) were more commonly found in the deceased group than survived group. In multivariable Cox regression analysis, after adjusting for clinical variables, increased subcutaneous fat index (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.47-0.66, P < 0.001) and increased pericardial fat index (HR = 0.47, 95% CI: 0.40-0.56, P < 0.001) were associated with longer overall survival. For stage I-III patients, increased subcutaneous fat index (HR = 0.62, 95% CI: 0.48-0.76, P < 0.001) and increased pericardial fat index (HR = 0.43, 95% CI: 0.34-0.54, P < 0.001) were associated with better 5-year overall survival rate. Similar results were recorded in stage IV patients. For patients with surgery, the prognostic value of increased subcutaneous fat index (HR = 0.60, 95% CI: 0.44-0.80, P = 0.001) and increased pericardial fat index (HR = 0.51, 95% CI: 0.38-0.68, P < 0.001) remained and predicted favourable overall survival. Non-surgical patients showed similar results as surgical patients. No association was noted between sarcopenia and overall survival (P > 0.05). CONCLUSIONS: Increased subcutaneous fat index and pericardial fat index were associated with a higher 5-year overall survival rate, independent of sarcopenia, in non-small cell lung cancer and may indicate a reduced risk of non-cancer-related death.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sarcopenia , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/patología , Sarcopenia/patología , Estudios Retrospectivos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X , Músculo Esquelético/patología , Tejido AdiposoRESUMEN
BACKGROUND AND PURPOSE: We investigated the dynamics of eosinophil depletion during definitive concurrent chemo-radiotherapy (CCRT) and their association with the prognosis of stage â ¡-â £a nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Fuzzy C-means algorithm (FCMA) assessed longitudinal trends in circulating eosinophil counts (CECs) of 1225 patients throughout the period of radical radiotherapy. The prognostic impact on patients' survival was evaluated with Kaplan-Meier analysis and Cox proportional risk model was used to determine the hazard ratio for adverse prognostic effects in grades of eosinophil depletion. The interactive effect of pre-treatment CECs and CCRT on outcomes was evaluated using HRs within the framework of Cox regression models. RESULTS: Three grades of eosinophil depletion, as defined by the interaction between dynamic types of CECs in the period of treatment and the value of CECs at the termination of treatment, significantly stratified the poor prognosis in terms of progression-free survival (PFS), overall survival (OS), and distant metastasis-free survival (DMFS) [1.57-fold (P = 0.001), 1.69-fold (P = 0.007), and 1.51-fold (P = 0.019) for G1, 2.4-fold (P < 0.001), 2.76-fold (P < 0.001), and 2.31-fold (P < 0.001) for G2, as compared with G0]. Furthermore, high levels of pre-treatment CECs acted as the strongest protective factor against severe depletion grade (G0 vs. G2, HR = 0.20, P = 0.005; G1 vs. G2, HR = 0.14, P < 0.001). However, compared with radiotherapy alone, the benefit from CCRT was attenuated in patients with high pre-treatment CECs. CONCLUSIONS: CECs reduction after treatment in patients with NPC may be helpful in the clinical setting to aid in assessing the prognosis for standard treatment of NPC.
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Background: The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric transcriptional repressors that play an essential role in developing and progressing diverse malignancies. However, the association of ZHX family expression with prognosis and immune infiltration in lung adenocarcinoma (LUAD) is still unclear. The current study aimed to investigate the relationship between ZHX family expression and clinical outcomes and immune infiltration in LUAD patients. Methods: ZHXs family expression was determined by using the Oncomine database and Cancer Cell Line Encyclopedia (CCLE). The impact of ZHXs family expression on prognosis was analyzed by using the Kaplan-Meier-plotter online database. The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to construct the interaction network based on the selected differentially expressed genes associated with ZHXs. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform the enrichment of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The functional state of the ZHXs family in diverse types of malignancies was determined by CancerSEA. The Tumor Immune Estimation Resource (TIMER) database was used to evaluate the association of the ZHXs family with immune cell infiltrates. ZHXs family expression was validated by the Gene Expression Omnibus (GEO) database and real-time polymerase chain reaction (RT-PCR) in 10 paired tumors and normal tissues. Results: ZHX1-3 expression level significantly decreased in LUAD compared with normal tissues. Attenuated ZHXs expression was significantly associated with unfavorable overall survival in LUAD patients. ZHX family members were positively associated with immune infiltration of monocytes, tumor-associated macrophages (TAMs), M1 and M2 macrophages in LUAD. ZHX family expression was also significantly related to a variety of immune marker sets in LUAD. GEO analysis and RT-PCR validated the significant decrease of ZHXs expression level in LUAD. Conclusions: The current study revealed that ZHX family expression was significantly correlated with unfavorable outcomes and immune infiltration in LUAD. The findings herein provide a promising basis for further study into the potential biological function of the ZHX family in LUAD and lay a foundation for developing therapeutic targets for LUAD patients.
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Objective: To investigate the effect of MALAT1 on the modulating the radiosensitivity of lung adenocarcinoma, through regulation of the expression of the miR-140/PD-L1 axis. Methods: The online databases UALCAN and dbDEMC were searched for the MALAT1 and miR-140 expressions in patients with lung adenocarcinoma (LUAD), respectively. Then analyze their relationship with overall survival rates separately in the UALCAN and ONCOMIR databases. A functional analysis was performed for A549 cells by transfecting small-interfering RNAs or corresponding plasmids after radiotherapy. Xenograft models of LUAD exposed to radiation were established to further observe the effects of MALAT1 on the radiosensitivity of LUAD. The luciferase assay and reverse transcription-polymerase chain reaction were performed to assess the interaction between miR-140 and MALAT1 or PD-L1. Results: MALAT1 were overexpressed in human LUAD tumor tissues and cell lines, while miR-140 were inhibited. MALAT1 knockdown or miR-140 increase suppressed cell proliferation and promoted cell apoptosis in LUAD after irradiation. LUAD xenograft tumor growth was also inhibited by MALAT1 knockdown combined with irradiation. miR-140 could directly bind with MALAT1 or PD-L1. Furthermore, MALAT1 knockdown inhibited PD-L1 mRNA and protein expressions by upregulating miR-140 in LUAD cells. Conclusion: MALAT1 may function as a sponge for miR-140a-3p to enhance the PD-L1 expression and decrease the radiosensitivity of LUAD. Our results suggest that MALAT1 might be a promising therapeutic target for the radiotherapy sensitization of LUAD.
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Pro-inflammatory cytokines upregulate the expression of the H2O2-producing NADPH oxidase dual oxidase 2 (DUOX2)2 which, when elevated, adversely affects survival from pancreatic ductal adenocarcinoma (PDAC). Because the cGAS-STING pathway is known to initiate pro-inflammatory cytokine expression following uptake of exogenous DNA, we examined whether activation of cGAS-STING could play a role in the generation of reactive oxygen species by PDAC cells. Here, we found that a variety of exogenous DNA species markedly increased the production of cGAMP, the phosphorylation of TBK1 and IRF3, and the translocation of phosphorylated IRF3 into the nucleus, leading to a significant, IRF3-dependent enhancement of DUOX2 expression, and a significant flux of H2O2 in PDAC cells. However, unlike the canonical cGAS-STING pathway, DNA-related DUOX2 upregulation was not mediated by NF-κB. Although exogenous IFN-ß significantly increased Stat1/2-associated DUOX2 expression, intracellular IFN-ß signaling that followed cGAMP or DNA exposure did not itself increase DUOX2 levels. Finally, DUOX2 upregulation subsequent to cGAS-STING activation was accompanied by the enhanced, normoxic expression of HIF-1α and VEGF-A as well as DNA double strand cleavage, suggesting that cGAS-STING signaling may support the development of an oxidative, pro-angiogenic microenvironment that could contribute to the inflammation-related genetic instability of pancreatic cancer.
Asunto(s)
Peróxido de Hidrógeno , Neoplasias Pancreáticas , Humanos , Oxidasas Duales/genética , Oxidasas Duales/metabolismo , Peróxido de Hidrógeno/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Transducción de Señal , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , ADN/metabolismo , Citocinas , Neoplasias Pancreáticas/metabolismo , Microambiente TumoralRESUMEN
Here, a rational strategy to achieve multifunctional N, S codoped carbon dots (N, S-CDs) is reported, aiming to improve the photoluminescence quantum yields (PLQYs) of the CDs. The synthesized N, S-CDs have excellent stability and emission properties independent of excitation wavelength. Through the introduction of S element doping, the fluorescence emission of CDs is red-shifted from 430 to 545 nm, and the corresponding PLQYs can be greatly enhanced from 11.2% to 65.1%. It is found that the doping of S elements causes an increase in the size of CDs and an elevated graphite N content, which may be the key factors to cause the redshift of fluorescence emission. Furthermore, the introduction of S element also serves to suppress the nonradiative transitions, which may be responsible for the elevated PLQYs. Besides, the synthesized N, S-CDs have certain solvent effect and can be applied to detect water content in organic solvents, and have strong sensitivity to alkaline environment. More importantly, the N, S-CDs can be used to achieve an "on-off-on" dual detection mode between Zr4+ and NO2 - . In addition, N, S-CDs combinedwith polyvinylpyrrolidone (PVP) can also be utilized as fluorescent inks for anti-counterfeiting applications.