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Radioresistance contributes to metastasis and recurrence in non-small cell lung cancer (NSCLC) patients. However, the underlying mechanism remains unclear. To provide novel clues, a complete multi-omics map of a radioresistant cancer cell line has been profiled. In this article, a lung adenocarcinoma cell line, radioresistant A549 (RA549), was generated by exposure to a series of irradiation. Subsequently, we adopted transcriptome, quantitative proteome and lysine 2-hydroxyisobutyrylome to construct a differential profile on the transcriptional to post-tanslational levels on A549 and RA549 cell lines, respectively. Our analysis revealed 920 significantly differentially expressed genes and 699 proteins. Furthermore, 2-hydroxyisobutyrylome identified 30,089 Khib modified sites on 4635 proteins, indicating that Khib modifications play vital role in regulating NSCLC radioresistance. Multi-omics combined analysis identified 19 significantly differentially expressed genes/proteins in total. Meanwhile, we found that EGFR, a well-known lung cancer-related receptor, was upregulated at both the protein and Khib modification levels in RA549. Further gain/loss of function experiments showed that Khib modified EGFR level positively correlates with NSCLC cell radioresistance. Taken together, our findings report that Khib-modified proteins enhanced resistance to radiation and represent promising therapeutic targets.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteoma , Tolerância a Radiação , Transcriptoma , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Tolerância a Radiação/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Células A549 , Receptores ErbB/metabolismo , Receptores ErbB/genética , ProteômicaRESUMO
BACKGROUND: Treatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) patients, especially those with non-sensitive genetic mutations, is hindered by limited drug delivery through the blood-brain barrier (BBB). This retrospective study explores the efficacy of systemic treatments during brain metastasis to radiotherapy evaluation window in improving patient survival. METHODS: In this retrospective cohort study, we evaluated 209 NSCLC patients with non-sensitive mutations and BMs, treated between 2016 and 2023 at two tertiary medical centers (Chongqing University Cancer Hospital and Guangxi Medical University Cancer Hospital). The patients were divided into three groups, namely chemotherapy alone (C; n = 95), chemotherapy plus immune checkpoint inhibitors (ICIs) (C + I; n = 62), and chemotherapy with ICIs and antiangiogenic therapy (A) (C + I + A; n = 52). Statistical analyses were performed using R software, version 4.3.3. Categorical variables were compared using Fisher's exact test, and survival curves were estimated with the Kaplan-Meier method and compared via the log-rank test. Univariate and multivariate Cox regression models were used to assess factors associated with overall survival (OS). Bayesian model averaging (BMA) was employed to address model uncertainty and improve result robustness. Subgroup analyses evaluated treatment-related mortality risk. RESULTS: From an initial cohort of 658 NSCLC patients with BMs, 209 were analyzed with a median age of 59; the majority were male (80.9%) and diagnosed with adenocarcinoma (78.9%). Univariate analysis identified significant variables influencing outcomes, including BMs radiotherapy EQD2, BMs count, local thoracic treatment, BMs radiotherapy field, intracranial response, and systemic treatment post-BMs diagnosis. The C + I + A regimen significantly improved median OS to 23.6 months compared to 11.4 months with C and 16.2 months with C + I, with a hazard ratio (HR) of 0.60 (95% CI: 0.43-0.82; P < 0.0001). The two-year OS rate was highest in the C + I + A group at 38.5%, versus 10.5% in C and 20.4% in C + I (P < 0.001). Cox regression and BMA analyses confirmed the stability of BMA in providing HR estimates, yielding area under the curve (AUC) values of 0.785 for BMA and 0.793 for the Cox model, with no significant difference in predictive performance. Subgroup analysis revealed a 71% mortality risk reduction with C + I + A (HR: 0.29; 95% CI: 0.18-0.47; P < 0.0001), showing consistent benefits regardless of patient sex, BMs count, extracranial metastases presence, and local thoracic treatments. Treatment sequence analysis indicated a median OS of 33.4 months for patients starting with A, though not statistically significant (HR: 0.59; P = 0.36). The overall incidence of radiation-induced brain injury was low at 3.3%, with rates in the C, C + I, and C + I + A groups being 3.2%, 4.8%, and 1.9%, respectively (P = 0.683). CONCLUSION: Our study demonstrates the significant benefit of the C + I + A combination therapy in improving OS and reducing mortality risk in NSCLC patients with non-sensitive gene-mutated BMs. The sequential administration of A followed by ICIs shows a promising synergistic effect with cranial radiotherapy, highlighting the potential for optimized treatment sequencing. These findings emphasize the efficacy of tailored combination therapies in complex oncological care and suggest that our approach could lead to meaningful improvements in clinical outcomes for this challenging patient population.
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Inibidores da Angiogênese , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Retrospectivos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/tratamento farmacológico , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , AdultoRESUMO
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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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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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 , Animais , Camundongos , Carcinoma Pulmonar de Lewis/radioterapia , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Indazóis/farmacologia , Macrófagos/metabolismo , Propionatos/farmacologia , Análise de Sequência de RNA , Microambiente Tumoral/genética , Análise de Célula Única , Quimiocina CCL8RESUMO
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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Linfócitos T CD8-Positivos , Células Matadoras Naturais , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Microambiente Tumoral , Animais , Células Matadoras Naturais/imunologia , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Linfócitos T CD8-Positivos/imunologia , Camundongos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Linfócitos do Interstício Tumoral/imunologia , Fenótipo , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologiaRESUMO
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.
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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 , Formação de Anticorpos , SARS-CoV-2 , Estudos Prospectivos , Neoplasias Hematológicas/complicações , Progressão da Doença , Imunoglobulina G , Anticorpos AntiviraisRESUMO
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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Zinc-finger proteins (ZNFs) constitute the largest transcription factor family in the human genome. The family functions in many important biological processes involved in tumorigenesis. In our research, we identified ZNF334 as a novel tumor suppressor of triple-negative breast cancer (TNBC). ZNF334 expression was usually reduced in breast cancerv (BrCa) tissues and TNBC cell lines MDA-MB-231 (MB231) and YCCB1. We observed that promoter hypermethylation of ZNF334 was common in BrCa cell lines and tissues, which was likely responsible for its reduced expression. Ectopic expression of ZNF334 in TNBC cell lines MB231 and YCCB1 could suppress their growth and metastatic capacity both in vitro and in vivo, and as well induce cell cycle arrest at S phase and cell apoptosis. Moreover, re-expression of ZNF334 in TNBC cell lines could rescue Epithelial-Mesenchymal Transition (EMT) process and restrain stemness, due to up-regulation of SFRP1, which is an antagonist of Wnt/ß-catenin signaling. In conclusion, we verified that ZNF334 had a suppressive function of TNBC cell lines by targeting the SFRP1/Wnt/ß-catenin signaling axis, which might have the potentials to become a new biomarker for diagnosis and treatment of TNBC patients.
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Neoplasias de Mama Triplo Negativas , Proteínas de Transporte , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Membrana , Neoplasias de Mama Triplo Negativas/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Breast cancer is the leading cause of cancer death in female. Until now, advanced breast cancer is still lack effective treatment strategies and reliable prognostic markers. In the present article, we introduced the physiologic and pathologic functions and regulation mechanisms of ZBTB28, a tumor suppressor gene, in breast cancer. ZBTB28 is frequently silenced in breast cancer due to promoter CpG methylation, and its expression is positively correlated with breast cancer patient survival. The antineoplastic effect of ZBTB28 in breast cancer was elucidated through a series of in vitro and in vivo measurements, including cell proliferation, apoptosis, cell cycle, epithelial mesenchymal transition (EMT), and growth of xenografts. Furthermore, ZBTB28 can directly regulate IFNAR to activate interferon-stimulated genes and potentiate macrophage activation. Ectopic ZBTB28 expression in breast cancer cells was sufficient to downregulate CD24 and CD47 to promote phagocytosis of macrophages, demonstrating that ZBTB28 was beneficial for the combination treatment of anti-CD24 and anti-CD47. Collectively, our results reveal a mode of action of ZBTB28 as a tumor suppressor gene and suggest that ZBTB28 is an important regulator of macrophage phagocytosis in breast cancer, holding promise for the development of novel therapy strategies for breast cancer patients.
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Neoplasias da Mama/genética , Antígeno CD24/genética , Antígeno CD47/genética , Fagocitose , Receptor de Interferon alfa e beta/genética , Proteínas Repressoras/genética , Animais , Neoplasias da Mama/imunologia , Antígeno CD24/imunologia , Antígeno CD47/imunologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptor de Interferon alfa e beta/imunologia , Proteínas Repressoras/imunologia , Células THP-1RESUMO
Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV-negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV-associated aggressive B-cell non-Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV-associated aggressive B-cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23-87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3-5) (62.7%) at diagnosis. Median CD4+ T-cell count at diagnosis was 191/µl (range, 4-1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122-4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027-19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589-1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500-6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347-0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti-lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV-associated DLBCL and BL.
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Infecções por HIV , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Doxorrubicina , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Lactato Desidrogenases , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: Nasopharyngeal carcinoma (NPC) is prevailing in Southern China, characterized by distinct geographical distribution. Aimed to predict the overall survival (OS) of patients with nasopharyngeal carcinoma, this study developed and validated nomograms considering demographic variables, hematological biomarkers, and oncogenic pathogens in China. METHODS: The clinicopathological and follow-up data of the nasopharyngeal carcinoma patients obtained from a prospective longitudinal cohort study in the Chongqing University Cancer Hospital between Jan 1, 2017 and Dec 31, 2019 ([Formula: see text]). Cox regression model was used to tested the significance of all available variables as prognostic factors of OS. And independent prognostic factors were identified based on multivariable analysis to model nomogram. Concordance index (C-index), area under the receiver operating characteristic (AUC), calibration curve, and decision curve analysis (DCA) were measured to assess the model performance of nomogram. RESULTS: Data was randomly divided into a training cohort (1227 observers, about 70% of data) and a validation group (408 observers, about 30% of data). At multivariable analysis, the following were independent predictors of OS in NPC patients and entered into the nomogram: age (hazard ratio [HR]: 1.03), stage (stage IV vs. stage I-II, HR: 4.54), radiotherapy (Yes vs. No, HR: 0.43), EBV ([Formula: see text] vs.[Formula: see text], HR: 1.92), LAR ([Formula: see text] vs.[Formula: see text], HR: 2.05), NLR ([Formula: see text] vs. [Formula: see text] HR: 1.54), and PLR ([Formula: see text] vs.[Formula: see text], HR: 1.79). The C-indexes for training cohort at 1-, 3- and 5-year were 0.73, 0.83, 0.80, respectively, in the validation cohort, the C-indexes were 0.74 (95% CI 0.63-0.86), 0.80 (95% CI 0.73-0.87), and 0.77 (95% CI 0.67-0.86), respectively. The calibration curve demonstrated that favorable agreement between the predictions of the nomograms and the actual observations in the training and validation cohorts. In addition, the decision curve analysis proved that the nomogram model had the highest overall net benefit. CONCLUSION: A new prognostic model to predict OS of patients with NPC was developed. This can offer clinicians treatment making and patient counseling. Furthermore, the nomogram was deployed into a website server for use.
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In recent years, photothermal materials that can convert light into heat energy have attracted extensive attention. In this work, we report a simple and effective approach to construct a self-cleaning photothermal superamphiphobic fabric. Dopamine (DA) can self-polymerize into polydopamine (PDA) and adhere to the surface of cotton fabric as a secondary reaction platform. Then, SiO2 nanoparticles were in situ grown on the PDA@fabric surface by the sol-gel method. The PDA clusters can not only provide good photothermal conversion performance but also be integrated with SiO2 to create micro-nano rough structures. Finally, the surface of SiO2 was modified by the long chain of fluorosilane to decrease the fabric surface energy, resulting in superamphiphobicity. The contact angles of water, ethylene glycol, and pump oil on the modified fabric surface could reach 161.1, 158.1, and 142.2°, respectively, making the fabric resistant to contamination by water, common beverages, and oil. Due to the adhesion of the PDA layer, the strong binding force between the fabric and SiO2 particles enabled the modified fabric to withstand various chemical and mechanical attacks, showing excellent mechanical robustness and harsh environmental stability. More importantly, the surface temperature of the modified fabric could be increased from 19.6 to 37.0 °C, which is close to the human body temperature, under the irradiation of simulated sunlight (I = 15 A, 300 s). The photothermal superamphiphobic fabrics with self-cleaning properties show great promise in the photothermal conversion field.
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Polímeros , Dióxido de Silício , Humanos , Indóis/química , Polímeros/química , Dióxido de Silício/química , ÁguaRESUMO
Callicarpa nudiflora, belonging to the family Verbenaceaae, is wildly used as a traditional Chinese herbal medicine (Luo-hua-zi-zhu) for hemostasis, antibiosis and antiphlogosis in clinic. However, the underlying chemical basis of C. nudiflora for the significant effects remains obscure. Hence, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry method was established for the characterization of multi-constituents in C. nudiflora. As a result, 57 chemical compounds were identified based on their retention times, accurate masses and MS/MS data, and 20 of them were uncovered for the first time in C. nudiflora. In addition, an optimized UHPLC fingerprint analysis, combined with chemometrics including similarity analysis, principal component analysis and partial least squares-discriminant analysis was developed for quality assessment and origin discrimination of C. nudiflora. Multivariate data analysis revealed the resemblances and differences of C. nudiflora related to regions, while partial least squares-discriminant analysis screened nine characteristic markers including luteoloside, acteoside, luteolin-4'-O-ß-D-glucopyranoside, pachypodol, isoquercitrin, nudifloside, 5,7,3',4'-tetrahydroxy-8-methoxy-6-C-ß-D-glucopyranosylflavone, 7α-acetoxysandaracopimaric acid and sandaracopimaric acid which contributed the most to the classification. This was the first report on the comprehensive profiling of chemical components in C. nudiflora, which helped to uncover the material basis of C. nudiflora and possess potential value for quality evaluation and clinical application purpose.
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Callicarpa , Medicamentos de Ervas Chinesas , Callicarpa/química , Espectrometria de Massas em Tandem , Luteolina , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/químicaRESUMO
OBJECTIVES: Although oral sulfate solution (OSS) has been revealed to be not only safe and efficacious but also noninferior to polyethylene glycol with ascorbic acid (PEG + ASC), it is unclear whether OSS can ultimately increase the polyp detection rate (PDR) and adenoma detection rate (ADR). We performed this meta-analysis to estimate the effect of OSS on PDR and ADR during colonoscopy. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) investigating the comparative effect of OSS versus PEG + ASC on the PDR and ADR during colonoscopy. Cecal intubation time (CIT), cecal intubation rate (CIR), and bowel preparation score were also evaluated. Review Manager (RevMan) version 5.3.0 was used to perform statistical analysis. RESULTS: Eight RCTs involving 2059 patients fulfilled the selection criteria. Meta-analysis suggested that OSS significantly increased the PDR (47.34% vs. 40.14%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.24, P = 0.01) and ADR (44.60% vs. 38.14%, RR 1.17, 95% CI 1.03-1.33, P = 0.01) during colonoscopy. Subgroup analysis showed that the beneficial effects of OSS on PDR and ADR were consistent among patients with mean age >55 years and with body mass index <25 kg/m2 receiving outpatient colonoscopy, morning colonoscopy, and the 2-L bowel preparation protocol. Meanwhile, patients receiving OSS had a beneficial bowel preparation score. CONCLUSION: Compared with polyethylene glycol-based regimens, the OSS bowel preparation regimen significantly increased the PDR and ADR in patients undergoing colonoscopy.
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Adenoma , Pólipos , Adenoma/diagnóstico , Catárticos , Colonoscopia/métodos , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis , Ensaios Clínicos Controlados Aleatórios como Assunto , SulfatosRESUMO
Carbon nanomaterials have elicited much research interest in the energy storage field, but most of them cannot be used at high temperatures. Thus, a supercapacitor with high energy and desired stability at high temperatures is urgently required. Herein, BCN nanotubes (BCNNTs) with excellent performance at high temperatures are generated on carbon fibers by optimizing the ratio of B and N. The nanotubes' morphology can effectively alleviate the structural damage caused by the rapid adsorption/desorption of the electrolyte during long-time charge/discharge cycles at high temperatures, thus improving the high-temperature cycle stability. The symmetric supercapacitors that are assembled with the binder-free BCNNT electrode in 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM·BF4 ) exhibited a high areal capacitance of 177.1 mF cm-2 at a current density of 5 mA cm-2 , and capacitance retention is maintained up to 86.1% for 5000 cycles at 100 °C. Moreover, the flexible supercapacitor based on BCNNTs in poly(vinylidenefluoride hexafluoropropylene)/EMIM·BF4 /succinonitrile gel electrolyte also exhibits good volumetric capacitance (1.98 mWh cm-3 at a current density of 5 mA cm-2 ) and cycling stability (92.6% retention after 200 charge/discharge cycles) at a temperature of 100 °C. This work shows that binder-free BCNNTs are promising materials for high-temperature flexible energy storage devices.
RESUMO
Plant male gametogenesis is a coordinated effort involving both reproductive tissues and sporophytic tissues, in which lipid metabolism plays an essential role. Although GDSL esterases/lipases have been well known as key enzymes for many plant developmental processes and stress responses, their functions in reproductive development remain unclear. Here, we report the identification of a rice male sterile2 (rms2) mutant in rice (Oryza sativa), which is completely male sterile due to the defects in tapetum degradation, cuticle formation in sporophytic tissues, and impaired exine and central vacuole development in pollen grains. RMS2 was map-based cloned as an endoplasmic reticulum-localized GDSL lipase gene, which is predominantly transcribed during early anther development. In rms2, a three-nucleotide deletion and one base substitution (TTGT to A) occurred within the GDSL domain, which reduced the lipid hydrolase activity of the resulting protein and led to significant changes in the content of 16 lipid components and numerous other metabolites, as revealed by a comparative metabolic analysis. Furthermore, RMS2 is directly targeted by the male fertility regulators Undeveloped Tapetum1 and Persistent Tapetal Cell1 both in vitro and in vivo, suggesting that RMS2 may serve as a key node in the rice male fertility regulatory network. These findings shed light on the function of GDSLs in reproductive development and provide a promising gene resource for hybrid rice breeding.
Assuntos
Lipase/metabolismo , Oryza/metabolismo , Oryza/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Lipase/genética , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reprodução/genética , Reprodução/fisiologiaRESUMO
OBJECTIVES: Continuous surveillance of bladder volume (BV) is beneficial during the treatment of various urogenital diseases because the bladder is always changing its position, size and even shape at different filling phases. For this purpose, we quantified the motion of the urinary bladder. METHODS: Daily ultrasound measurements and weekly cone-beam computed tomography scans were obtained from 89 patients in the supine position. BV, bladder centroid positions, and triaxial lengths in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were compared across different time points. RESULTS: BV linearly increased over time, and the mean urinary filling rate (vtot) was correlated with the patients' age and water consumption. The greatest bladder centroid motion occurred longitudinally, with less movement observed laterally. The maximum bladder centroid movement was 18.8 ± 2.2 mm inferiorly and 1.8 ± 0.9 mm posteriorly for every 10% decrease in BV. The rates of changes in triaxial lengths differed across the 4 filling phases. The rate was the largest at a BV range of 10-80 mL, especially in the LR direction, with values of 5.9 ± 1.0, 3.6 ± 1.0, and 3.9 ± 1.0 mm per every 10-mL BV increase for LR, AP, and SI, respectively. With bladder filling (<80 mL), the maximum increase in triaxial length was observed in the SI direction and the rates of all changes considerably decreased, especially at BV > 600 mL. CONCLUSION: The vtot could be used to evaluate the temporal changes in the bladder. The spatial changes should be assessed according to different filling phases based on the centroid position and triaxial lengths.
Assuntos
Bexiga Urinária/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estado de Hidratação do Organismo , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ultrassonografia , Bexiga Urinária/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
Dual oxidase 2 (DUOX2) generates H2O2 that plays a critical role in both host defense and chronic inflammation. Previously, we demonstrated that the proinflammatory mediators IFN-γ and LPS enhance expression of DUOX2 and its maturation factor DUOXA2 through STAT1- and NF-κBâmediated signaling in human pancreatic cancer cells. Using a panel of colon and pancreatic cancer cell lines, we now report the induction of DUOX2/DUOXA2 mRNA and protein expression by the TH2 cytokine IL-4. IL-4 activated STAT6 signaling that, when silenced, significantly decreased induction of DUOX2. Furthermore, the TH17 cytokine IL-17A combined synergistically with IL-4 to increase DUOX2 expression in both colon and pancreatic cancer cells mediated, at least in part, by signaling through NF-κB. The upregulation of DUOX2 was associated with a significant increase in the production of extracellular H2O2 and DNA damage-as indicated by the accumulation of 8-oxo-dG and γH2AX-which was suppressed by the NADPH oxidase inhibitor diphenylene iodonium and a DUOX2-specific small interfering RNA. The clinical relevance of these experiments is suggested by immunohistochemical, microarray, and quantitative RT-PCR studies of human colon and pancreatic tumors demonstrating significantly higher DUOX2, IL-4R, and IL-17RA expression in tumors than in adjacent normal tissues; in pancreatic adenocarcinoma, increased DUOX2 expression is adversely associated with overall patient survival. These data suggest a functional association between DUOX2-mediated H2O2 production and induced DNA damage in gastrointestinal malignancies.