RESUMO
Photonic crystals with specific wavelengths can realize surface-enhanced excitation and emission intensities of fluorophores and enhance the fluorescence signals of fluorescent molecules. Herein, stretchable photonic crystals with good mechanochromic properties provide continuously adjustable forbidden wavelengths by stretching to change the lattice spacing, with reflectance peaks blue-shifted up to 110 nm to match indicators of different wavelengths and produce differentiated optical enhancement effects. Glycoproteins are significantly identified as clinical markers. However, the wide participation of glycoproteins in various life processes poses enormous complexity and critical challenges for rapid, facile, high-throughput, and accurate clinical analysis or health assessment. In this work, we proposed a stretchable photonic crystal-assisted glycoprotein identification approach for early ovarian cancer diagnosis. Stretchable photonic crystals can provide rich optical information to efficiently identify glycoproteins in complex matrices. A double-indicator fluorescence sensor was designed to respond to the protein trunk and oligosaccharide segment of glycoproteins separately for improved recognition accuracy. Seven typical glycoproteins could be discriminated from proteins, saccharides, or mixture interferents. Clinical ovarian cancer samples for early, intermediate, and advanced ovarian cancer and healthy subjects were verified with 100% accuracy. This strategy of stretchable photonic crystal-assisted glycoprotein identification provides an effective method for accurate, rapid ovarian cancer diagnosis and timely clinical treatment.
Assuntos
Glicoproteínas , Neoplasias Ovarianas , Feminino , Neoplasias Ovarianas/diagnóstico , Humanos , Glicoproteínas/análise , Fótons , Corantes Fluorescentes/química , Biomarcadores Tumorais/análise , CristalizaçãoRESUMO
OBJECTIVE: Inflammation, malnutrition, and cancer are intricately interconnected. Despite this, only a few studies have delved into the relationship between inflammatory malnutrition and the risk of death among cancer survivors. This study aimed to specifically investigate the association between the categorically defined Naples prognostic score (NPS) and the prognosis of cancer survivors. METHODS: Data from 42,582 participants in the National Health and Nutrition Examination Survey (NHANES, 1999-2018) were subjected to analysis. Naples prognostic scores (NPS) were computed based on serum albumin (ALB), total cholesterol (TC), neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR), and participants were stratified into three groups accordingly. Cancer status was ascertained through a self-administered questionnaire, while mortality data were sourced from the National Death Index up to December 31, 2019. Multiple logistic regression was employed to estimate the odds ratio (OR) with a 95% confidence interval (CI) between NPS and cancer prevalence within the U.S. community population. Kaplan-Meier survival analysis and the Log-rank test were utilized to compare survival disparities among the three groups. Additionally, Cox proportional regression was utilized to estimate the hazard ratio (HR) with a 95% CI. RESULTS: The incidence of cancers was 9.86%. Among the participants, 8140 individuals (19.1%) were classified into Group 0 (NPS 0), 29,433 participants (69.1%) into Group 1 (NPS 1 or 2), and 5009 participants (11.8%) into Group 2 (NPS 3 or 4). After adjusting for confounding factors, the cancer prevalence for the highest NPS score yielded an odds ratio (OR) of 1.64 (95% CI: 1.36, 1.97) (P(for trend) < 0.05). In comparison to cancer survivors in Group 0, those with the highest NPS had adjusted hazard ratios (HRs) of 2.57 (95% CI: 1.73, 3.84) for all-cause mortality, 3.44 (95% CI: 1.64, 7.21) for cardiovascular mortality, 1.60 (95% CI: 1.01, 2.56) for cancer mortality, and 3.15 (95% CI: 1.74, 5.69) for other causes of mortality (All P(for trend) < 0.05). These associations remained consistent when stratified by age, sex, race, and body mass index. CONCLUSIONS: This study indicates that the Naples prognostic score (NPS), serving as a novel prognostic metric integrating inflammation and nutritional status, is closely linked to cancer prognosis within the general population.
Assuntos
Sobreviventes de Câncer , Neoplasias , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Sobreviventes de Câncer/estatística & dados numéricos , Prognóstico , Pessoa de Meia-Idade , Neoplasias/mortalidade , Idoso , Adulto , Inflamação , Neutrófilos , Desnutrição/epidemiologia , Colesterol/sangue , Estados Unidos/epidemiologia , Albumina Sérica/análise , Albumina Sérica/metabolismo , Monócitos/metabolismo , Linfócitos/metabolismoRESUMO
Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at the cellular level, and the therapies of nanozyme for several typical metabolic diseases and underlying mechanisms are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, and others. Finally, the pharmacokinetics, safety analysis, challenges, and outlooks for the application of nanozyme are also presented. This review will provide some instructive perspectives on nanozyme and promote the development of enzyme-mimicking strategies in metabolic disease therapy.
Assuntos
Doenças Metabólicas , Estresse Oxidativo , Espécies Reativas de Oxigênio , Humanos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Animais , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Nanopartículas/química , Enzimas/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Obesidade/metabolismo , Obesidade/tratamento farmacológicoRESUMO
BACKGROUND: To evaluate the clinical efficacy of sublingual-specific immunotherapy (SLIT) and pulmonary function in children with allergic rhinitis and asthma before and after puberty. METHODS: This retrospective analysis included 136 patients aged 4-18 years with allergic asthma and rhinitis who received two years of SLIT treatment. Patients were divided into two groups based on age: the prepubertal group (4-10 years old) and the pubertal group (11-18 years old). After half a year, one year, and two years of SLIT, the total nasal symptom score (TNSS), total rhinitis medication score (TRMS), daytime asthma symptom score (DASS), nighttime asthma symptom score (NASS), total asthma medication score (TAMS), asthma control test (ACT), and peak expiratory flow rate (PEF%) were evaluated and compared with the baseline before treatment. RESULTS: In both groups, TNSS, TRMS, DASS, NASS, TAMS, ACT, and PEF% improved significantly after half a year, one year, and two years of SLIT treatment. After half a year of treatment, prepubertal patients showed better therapy for TNSS, DASS, NASS, and TAMS compared to the pubertal group. The TAMS of the pubertal group was higher than that of the prepubertal group after one year of treatment. Finally, the PEF% showed better therapy compared to the pubertal group. CONCLUSION: SLIT treatment with Dermatophagoides farinae drops can effectively control the symptoms of rhinitis and asthma in children with allergic rhinitis and asthma before and after puberty, reduce the use of symptomatic drugs, significantly improve the pulmonary function of patients, and have better effects on asthma in prepubertal children than in adolescents.
RESUMO
Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.
Assuntos
Esternotomia , Infecção da Ferida Cirúrgica , Humanos , Masculino , Estudos de Casos e Controles , Esternotomia/efeitos adversos , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Idoso , Fatores de Tempo , Incidência , Esterno/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversosRESUMO
The known YAP inhibitor verteporfin is capable of repressing IL-17A production in Th17 cells. However, this effect is mediated independently of YAP and can ameliorate Th17-mediated experimental autoimmune encephalomyelitis (EAE) upon in vivo administration. The data suggest verteprofin's mode of action for the design of novel therapeutic autoimmune disease intervention.
Assuntos
Encefalomielite Autoimune Experimental , Células Th17 , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Verteporfina/farmacologiaRESUMO
BACKGROUND: Concomitant diseases often occur in cancer patients and are important in decision-making regarding treatments. However, information regarding the prognostic relevance of comorbidities for mortality risk is still limited among Chinese gastric cancer (GC) patients. This study aimed to investigate the association between comorbidities and 3-year mortality risk. METHODS: This retrospective study enrolled 376 GC patients undergoing radical gastrectomy at the Affiliated Zhongshan Hospital of Dalian University from January 2011 to December 2019. Demographic and clinicopathological information and treatment outcomes were collected. Patients were divided into low-, moderate- and high-risk comorbidity groups based on their Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) scores. Kaplan-Meier survival and Cox regression analyses were used to examine 3-year overall survival (OS) and mortality risk for each group. RESULTS: The median follow-up time was 43.5 months, and 40.2% (151/376) of GC patients had died at the last follow-up. There were significant differences in OS rates between ACCI-based comorbidity groups (76.56; 64.51; 54.55%, log-rank P = 0.011) but not between CCI-based comorbidity groups (log-rank P = 0.16). The high-risk comorbidity group based on the ACCI remained a significant prognostic factor for 3-year OS in multivariate analysis, with an increased mortality risk (hazard ratio [HR], 1.99; 95% CI, 1.15-3.44). Subgroup analysis revealed that this pattern only held for male GC patients but not for female patients. CONCLUSION: The present study suggested that high-risk comorbidities were significantly associated with a higher mortality risk, particularly in Chinese male GC patients. Moreover, the ACCI score was an independent prognostic factor of long-term mortality.
Assuntos
Neoplasias Gástricas , Humanos , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia , Fatores de Risco , Prognóstico , ComorbidadeRESUMO
Among the approximately 20 million patients with drug-resistant epilepsy (DRE) worldwide, the vast majority can benefit from surgery to minimize seizure reduction and neurological impairment. Precise preoperative localization of epileptogenic zone (EZ) and complete resection of the lesions can influence the postoperative prognosis. However, precise localization of EZ is difficult, and the structural and functional alterations in the brain caused by DRE vary by etiology. Neuroimaging has emerged as an approach to identify the seizure-inducing structural and functional changes in the brain, and magnetic resonance imaging (MRI) and positron emission tomography (PET) have become routine noninvasive imaging tools for preoperative evaluation of DRE in many epilepsy treatment centers. Multimodal neuroimaging offers unique advantages in detecting EZ, especially in improving the detection rate of patients with negative MRI or PET findings. This approach can characterize the brain imaging characteristics of patients with DRE caused by different etiologies, serving as a bridge between clinical and pathological findings and providing a basis for individualized clinical treatment plans. In addition to the integration of multimodal imaging modalities and the development of special scanning sequences and image post-processing techniques for early and precise localization of EZ, the application of deep machine learning for extracting image features and deep learning-based artificial intelligence have gradually improved diagnostic efficiency and accuracy. These improvements can provide clinical assistance for precisely outlining the scope of EZ and indicating the relationship between EZ and functional brain areas, thereby enabling standardized and precise surgery and ensuring good prognosis. However, most existing studies have limitations imposed by factors such as their small sample sizes or hypothesis-based study designs. Therefore, we believe that the application of neuroimaging and post-processing techniques in DRE requires further development and that more efficient and accurate imaging techniques are urgently needed in clinical practice. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.
RESUMO
A major challenge for cancer immunotherapy is sustaining T-cell activation and recruitment in immunosuppressive solid tumors. Here, we report that the levels of the Hippo pathway effector Yes-associated protein (Yap) are sharply induced upon the activation of cluster of differentiation 4 (CD4)-positive and cluster of differentiation 8 (CD8)-positive T cells and that Yap functions as an immunosuppressive factor and inhibitor of effector differentiation. Loss of Yap in T cells results in enhanced T-cell activation, differentiation, and function, which translates in vivo to an improved ability for T cells to infiltrate and repress tumors. Gene expression analyses of tumor-infiltrating T cells following Yap deletion implicates Yap as a mediator of global T-cell responses in the tumor microenvironment and as a negative regulator of T-cell tumor infiltration and patient survival in diverse human cancers. Collectively, our results indicate that Yap plays critical roles in T-cell biology and suggest that Yap inhibition improves T-cell responses in cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas de Ciclo Celular/fisiologia , Quimiotaxia de Leucócito/genética , Linfócitos T/fisiologia , Microambiente Tumoral/imunologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Imunoterapia Adotiva , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Microambiente Tumoral/genética , Proteínas de Sinalização YAPRESUMO
OBJECTIVES: To develop and validate a CT-based deep learning radiomics nomogram (DLRN) for outcome prediction in clear cell renal cell carcinoma (ccRCC), and its performance was compared with the Stage, Size, Grade, and Necrosis (SSIGN) score, the University of California, Los Angeles, Integrated Staging System (UISS), the Memorial Sloan-Kettering Cancer Center (MSKCC), and the International Metastatic Renal Cell Database Consortium (IMDC). METHODS: A multicenter of 799 localized (training/ test cohort, 558/241) and 45 metastatic ccRCC patients were studied. A DLRN was developed for predicting recurrence-free survival (RFS) in localized ccRCC patients, and another DLRN was developed for predicting overall survival (OS) in metastatic ccRCC patients. The performance of the two DLRNs was compared with that of the SSIGN, UISS, MSKCC, and IMDC. Model performance was assessed with Kaplan-Meier curves, time-dependent area under the curve (time-AUC), Harrell's concordance index (C-index), and decision curve analysis (DCA). RESULTS: In the test cohort, the DLRN achieved higher time-AUCs (0.921, 0.911, and 0.900 for 1, 3, and 5 years, respectively), C-index (0.883), and net benefit than SSIGN and UISS in predicting RFS for localized ccRCC patients. The DLRN provided higher time-AUCs (0.594, 0.649, and 0.754 for 1, 3, and 5 years, respectively) than MSKCC and IMDC in predicting OS for metastatic ccRCC patients. CONCLUSIONS: The DLRN can accurately predict outcomes and outperformed the existing prognostic models in ccRCC patients. CLINICAL RELEVANCE STATEMENT: This deep learning radiomics nomogram may facilitate individualized treatment, surveillance, and adjuvant trial design for patients with clear cell renal cell carcinoma. KEY POINTS: ⢠SSIGN, UISS, MSKCC, and IMDC may be insufficient for outcome prediction in ccRCC patients. ⢠Radiomics and deep learning allow for the characterization of tumor heterogeneity. ⢠The CT-based deep learning radiomics nomogram outperforms the existing prognostic models in ccRCC outcome prediction.
Assuntos
Carcinoma de Células Renais , Aprendizado Profundo , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Prognóstico , Nomogramas , Neoplasias Renais/diagnóstico por imagem , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X , Estudos RetrospectivosRESUMO
BACKGROUND: The laparoscopic and open approaches have comparable safety and oncological efficacy to treat early (T1b or T2) stage incidental gallbladder cancer (IGBC). However, their effects on T3 stage or above tumors unclear. METHODS: Data of IGBC patients who underwent radical re-resection were retrospectively analyzed. Demographic characteristics, surgical variables, and tumor characteristics were evaluated for association with survival. RESULTS: We analyzed retrospectively 201 patients (72 men, 129 women; median age 63 years; range, 36-85 years). 84 underwent laparoscopic re-resection and 117 underwent open surgery. The 5-year OS post-resection was 74.7%, with a median survival of 74.52 months. The median OS (73.92 months vs. 77.04 months, P = 0.67), and disease-free survival (72.60 months vs. 71.09 months, P = 0.18) were comparable between the laparoscopic re-resection and open surgery groups. The survival of patients with T1/T2 (median: 85.50 months vs. 80.14 months; P = 0.67) and T3 (median: 68.56 months vs. 58.85 months; P = 0.36) disease were comparable between the open re-resection and laparoscopic re-resection groups even after PS matching. Open surgery group lost significantly more blood, while laparoscopic surgery took longer. The postsurgical stay in the laparoscopic re-resection group was significantly shorter. Combined extrahepatic bile duct resection, gallbladder perforation, pT, pStage, histological grade, microscopic liver invasion, status of the resected margin, and adjuvant therapy comprised significant independent prognostic indicators for IGBC. CONCLUSIONS: Laparoscopic and open surgery can achieve similar short and long-term outcomes for T3 IGBC; however, careful surgical manipulation is necessary to avoid secondary injuries.
Assuntos
Adenocarcinoma , Colecistectomia Laparoscópica , Neoplasias da Vesícula Biliar , Laparoscopia , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Reoperação , Adenocarcinoma/cirurgia , Achados IncidentaisRESUMO
Adipic acid is an industrially important chemical, but the current approach to synthesize it can be of serious pollution to the environment. Rencently, bio-based production of adipic acid has significantly advanced with the development of metabolic engineering and synthetic biology. However, genetic heterogeneity-caused decrease of product titer has largely limited the industrialization of chemicals like adipic acid. Therefore, in the attempt to overcome this challenge, we constitutively expressed the reverse adipate degradation pathway, designed and optimized an adipic acid biosensor, and established a high-throughput screening platform to screen for high-performance strains based on the optimized biosensor. Using this platform, we successfully screened a strain with an adipic acid titer of 188.08 mg·L-1. Coupling the screening platform with fermentation optimization, the titer of adipic acid reached 531.88 mg·L-1 under shake flask fermentation, which achieved an 18.78-fold improvement comparing to the initial strain. Scale-up fermentation in a 5-L fermenter utilizing the screened high-performance strain was eventually conducted, in which the adipic acid titer reached 3.62 g·L-1. Overall, strategies developed in this study proved to be a potentially efficient method in reducing the genetic heterogeneity and was expected to provide guidance in helping to build a more efficient industrial screening process. KEY POINTS: ⢠Developed a fine-tuned adipic acid biosensor. ⢠Established a high-throughput screening platform to screen high-performance strains. ⢠The titer of adipic acid reached 3.62 g·L-1 in a 5-L fermenter.
RESUMO
BACKGROUND: Peripheral nerve damage causes neuroinflammation, which plays a critical role in establishing and maintaining neuropathic pain (NeP). The mechanisms contributing to neuroinflammation remain poorly elucidated, and pharmacological strategies for NeP are limited. Thus, in this study, we planned to explore the possible link between astrocyte senescence and NeP disorders following chronic sciatic nerve injury. METHODS: An NeP animal model was established by inducing chronic constrictive injury (CCI) to the sciatic nerve in adult rats. A senolytic drug combination of dasatinib and quercetin was gavaged daily from the first postoperative day until the end of the study. Paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL) were evaluated to assess behaviors in response to pain in the experimental rats. Senescence-associated ß-galactosidase staining, western blot analysis, and immunofluorescence were applied to examine the levels of proinflammatory factors and severity of the senescence-like response in the spinal cord. Lipopolysaccharide (LPS) was administered to induce senescence of spinal astrocytes in primary cultures in vitro, to explore the potential impacts of senescence on the secretion of proinflammatory factors. Furthermore, single-cell RNA sequencing (scRNA-seq) was conducted to identify senescence-related molecular responses in spinal astrocytes under neuropathic pain. RESULTS: Following sciatic nerve CCI, rats exhibited reduced PMWT and PTWL, increased levels of spinal proinflammatory factors, and an enhanced degree of senescence in spinal astrocytes. Treatment with dasatinib and quercetin effectively attenuated spinal neuroinflammation and mitigated the hypersensitivities of the rats subjected to sciatic nerve CCI. Mechanistically, the dasatinib-quercetin combination reversed senescence in LPS-stimulated primary cultured astrocytes and decreased the levels of proinflammatory factors. The scRNA-seq data revealed four potential senescence-related genes in the spinal astrocyte population, and the expression of clusterin (CLU) protein was validated via in vitro experiments. CONCLUSION: The findings indicate the potential role of astrocyte senescence in neuroinflammation following peripheral nerve injury, and suggest that targeting CLU activation in astrocytes might provide a novel therapeutic strategy to treat NeP.
Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Astrócitos/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Dasatinibe/metabolismo , Doenças Neuroinflamatórias , Lipopolissacarídeos/farmacologia , Quercetina/farmacologia , Quercetina/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/metabolismoRESUMO
We demonstrated the optical frequency transfer over a 96 km urban business network in Shanghai. The key factors affecting the optical frequency transmission system, such as fiber link quality, feedback compensation strength, and out-of-loop fiber temperature variation, are studied for the urban fiber link characteristics. The effective suppression technique of complex urban fiber link noise with different feedback compensation parameters is studied. With active phase noise suppression, the optical frequency stability can reach 1.9×10-16 at 1 s and 2.2×10-18 at 10,000 s over a 96 km urban fiber link. This work potentially plays an important role in optical clock frequency comparison, and it makes a good foundation for future research on long-distance optical frequency transfer over an urban business network.
RESUMO
BACKGROUND: Existing evidence shows that there is an independent correlation between nephrolithiasis and gout, and hyperuricemia is the most important risk factor for gout. However, hyperuricemia was often used as an accompanying symptom of gout to explore its association with nephrolithiasis, there were few studies to explore whether hyperuricemia itself or serum uric acid (SUA) is related to the risk of nephrolithiasis. Evidence on the relationship between hyperuricemia and nephrolithiasis is still insufficient. METHODS: A total of 22,303 participants aged 30 to 79 years who participated in the China Multi-Ethnic Cohort (CMEC) study in Yunnan Province from May 2018 to September 2019 were included in the study. All participants received standardized face-to-face interviews, medical examinations, and biochemical examinations. Logistic regression was used to estimate the association between hyperuricemia and nephrolithiasis, and a restricted cubic spline (RCS) model was used to explore the dose-response relationship between SUA and the risk of nephrolithiasis. RESULTS: 14.5% of all participants were diagnosed with hyperuricemia, and 12.1% were diagnosed with nephrolithiasis. After adjusting for all potential confounders, the OR (95%CI) for nephrolithiasis in participants with hyperuricemia compared with participants without hyperuricemia was 1.464 (1.312,1.633), p < 0.001. Restricted cubic spline regression analysis showed that the risk of nephrolithiasis increased with the increase of SUA, and when the level of SUA is higher than 356 µmol/L in males and higher than 265 µmol/L in females, there is a dose-response relationship between the increase of SUA and the risk of nephrolithiasis in both males and females (p for nonlinearity = 0.1668, p for nonlinearity = 0.0667). CONCLUSION: Asymptomatic hyperuricemia is associated with an increased risk of developing nephrolithiasis. Before reaching the diagnostic criteria for hyperuricemia, the risk of nephrolithiasis rises with the increase in SUA. This suggests that controlling SUA levels may be significant for the prevention of nephrolithiasis.
Assuntos
Gota , Hiperuricemia , Nefrolitíase , Masculino , Feminino , Humanos , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Ácido Úrico , Estudos Transversais , China/epidemiologia , Gota/complicações , Gota/epidemiologia , Fatores de Risco , Nefrolitíase/epidemiologia , Nefrolitíase/complicaçõesRESUMO
Background: DNA methylation patterns have been found to be distinct between tumor and normal patients. However, the effect of DNA demethylation enzymes, ten eleven translocation (TET) proteins, has not been comprehensively characterized in liver cancer. In this research, we sought to unravel the linkage of TET proteins with prognosis, immune characteristics and biological pathways in hepatocellular carcinoma (HCC). Materials and Methods: Four independent datasets with gene expression data and clinical data of HCC samples were downloaded from public databases. CIBERSORT, single sample Gene Set Enrichment Analysis (ssGSEA), MCP-counter, and TIMER were implemented to evaluate immune cell infiltration. limma was employed to screen differentially expressed genes (DEGs) between two groups. The demethylation-related risk model was established by using univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO), and stepwise Akaike information criterion (stepAIC). Results: TET1 was significantly higher expressed in tumor samples than that in normal samples. HCC patients with advanced stages (III+IV) and grades (G3+G4) had higher TET1 expression compared to early stages (I+II) and grades (G1+G2). HCC samples with high TET1 expression had worse prognosis than that with low expression. High and low TET1 expression groups had distinct immune cell infiltration and response to immunotherapy and chemotherapy. We identified 90 DEGs related to DNA demethylation in high vs. low TET1 expression groups. Furthermore, we established a risk model based on 90 DEGs containing seven key prognostic genes (SERPINH1, CDC20, HACD2, SPHK1, UGT2B15, SLC1A5, and CYP2C9) with effectiveness and robustness in predicting HCC prognosis. Conclusions: Our study suggested TET1 as a potential indicator in HCC progression. TET1 was closely involved in immune infiltration and activation of oncogenic pathways. The DNA demethylation-related risk model was potential to be applied for predicting HCC prognosis in clinics.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Ciclo Celular , Metilação de DNA/genética , Bases de Dados Factuais , Prognóstico , Biomarcadores Tumorais , Antígenos de Histocompatibilidade Menor , Sistema ASC de Transporte de Aminoácidos , Oxigenases de Função Mista , Proteínas Proto-OncogênicasRESUMO
PURPOSE: To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1ß (IL-1ß), IL-19, and IL-20. METHODS: Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1ß, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. RESULTS: Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1ß promoted osteogenesis but inhibited adipogenesis. CONCLUSION: IL-1ß, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1ß, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis.
Assuntos
Ligamento Amarelo , Estenose Espinal , Espondilolistese , Humanos , Adipogenia , Osteogênese , Interleucina-1beta/farmacologia , Estenose Espinal/patologia , Ligamento Amarelo/patologia , Espondilolistese/patologia , Diferenciação Celular , Células-TroncoRESUMO
Pathogen detection and control have long presented formidable challenges in the domains of medicine and public health. This review paper underscores the potential of nanozymes as emerging bio-mimetic enzymes that hold promise in effectively tackling these challenges. The key features and advantages of nanozymes are introduced, encompassing their comparable catalytic activity to natural enzymes, enhanced stability and reliability, cost effectiveness, and straightforward preparation methods. Subsequently, the paper delves into the detailed utilization of nanozymes for pathogen detection. This includes their application as biosensors, facilitating rapid and sensitive identification of diverse pathogens, including bacteria, viruses, and plasmodium. Furthermore, the paper explores strategies employing nanozymes for pathogen control, such as the regulation of reactive oxygen species (ROS), HOBr/Cl regulation, and clearance of extracellular DNA to impede pathogen growth and transmission. The review underscores the vast potential of nanozymes in pathogen detection and control through numerous specific examples and case studies. The authors highlight the efficiency, rapidity, and specificity of pathogen detection achieved with nanozymes, employing various strategies. They also demonstrate the feasibility of nanozymes in hindering pathogen growth and transmission. These innovative approaches employing nanozymes are projected to provide novel options for early disease diagnoses, treatment, and prevention. Through a comprehensive discourse on the characteristics and advantages of nanozymes, as well as diverse application approaches, this paper serves as a crucial reference and guide for further research and development in nanozyme technology. The expectation is that such advancements will significantly contribute to enhancing disease control measures and improving public health outcomes.
Assuntos
Saúde Pública , Reprodutibilidade dos Testes , Cinética , Espécies Reativas de OxigênioRESUMO
Genetically modified (GM) maize is one of the earliest GM crops to have achieved large-scale commercial cultivation globally, and it is of great significance to excel in the development and implementation of safety policy regarding GM, and in its technical oversight. This article describes the general situation regarding genetically modified maize, including its varieties, applications, relevant laws and regulations, and so on. From a technical point of view, we summarize and critically analyze the existing methods for detecting nucleic acid levels in genetically modified maize. The nucleic acid extraction technology used for maize is explained, and the introduction of traditional detection techniques, which cover variable-temperature and isothermal amplification detection technology and gene chip technology, applications in maize are described. Moreover, new technologies are proposed, with special attention paid to nucleic acid detection methods using sensors. Finally, we review the current limitations and challenges of GM maize nucleic acid testing and share our vision for the future direction of this field.
Assuntos
Técnicas de Amplificação de Ácido Nucleico , Zea mays , Plantas Geneticamente Modificadas/genética , Zea mays/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Produtos Agrícolas/genética , TecnologiaRESUMO
AIMS: This study aimed to explore the relationship between workplace bullying among nurses and their professional quality of life, as well as the mediating role of coping styles between the two factors. BACKGROUND: In China, the overall status of nurses' professional quality of life is not optimistic, and the problems of low compassion satisfaction and high compassion fatigue persist. Workplace bullying, which is a serious global issue, can negatively impact the mental health and professional quality of nurses. However, it has still not attracted enough attention from managers. METHODS: The study used a cross-sectional research design and surveyed 297 clinical nurses from two tertiary grade A hospitals in Wuhan, China. Data were collected through an online questionnaire survey from March to May 2022. The data were analyzed using descriptive statistical methods, including Pearson correlation analysis and structural equation modeling. RESULTS: The score for nurses' workplace bullying was 38.72 ± 12.30. The scores for the three dimensions of professional quality of life were 27.56 ± 4.79 for compassion satisfaction, 30.51 ± 4.33 for burnout, and 28.47 ± 4.65 for secondary trauma stress. The scores for positive coping style and negative coping style were 34.59 ± 5.72 and 20.34 ± 5.08 points, respectively. Workplace bullying had a direct negative effect on compassion satisfaction, as well as positive direct effects on burnout and secondary traumatic stress. Coping styles played a mediating effect between workplace bullying and the pairwise relationships of compassion satisfaction, burnout, and secondary trauma stress. CONCLUSION: Workplace bullying hurts nurses' professional quality of life while coping styles plays an mediating role between workplace bullying and professional quality of life. Nursing managers can improve nurses' professional quality of life by reducing workplace bullying and enhancing positive coping style. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers can employ management wisdom and techniques to mitigate the presence and detrimental effects of workplace bullying. This, in turn, promotes a positive work environment and enhances the professional quality of life for nurses.