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Optogenetics-based integrated photoelectrodes with high spatiotemporal resolution play an important role in studying complex neural activities. However, the photostimulation artifacts caused by the high level of integration and the high impedance of metal recording electrodes still hinder the application of photoelectrodes for optogenetic studies of neural circuits. In this study, a neural optrode fabricated on sapphire GaN material was proposed, and 4 µLEDs and 14 recording microelectrodes were monolithically integrated on a shank. Poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate and multiwalled carbon nanotubes (PEDOT:PSS-MWCNT) and poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT-GO) composite films were deposited on the surface of the recording microelectrode by electrochemical deposition. The results demonstrate that compared with the gold microelectrode, the impedances of both composite films reduced by more than 98%, and the noise amplitudes decreased by 70.73 and 87.15%, respectively, when exposed to light stimulation. Adjusting the high and low levels, we further reduced the noise amplitude by 48.3%. These results indicate that modifying the electrode surface by a polymer composite film can effectively enhance the performance of the microelectrode and further promote the application of the optrode in the field of neuroscience.
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Background: Cone-beam computed tomography (CBCT) is a convenient method for adaptive radiation therapy (ART), but its application is often hindered by its image quality. We aim to develop a unified deep learning model that can consistently enhance the quality of CBCT images across various anatomical sites by generating synthetic CT (sCT) images. Methods: A dataset of paired CBCT and planning CT images from 135 cancer patients, including head and neck, chest and abdominal tumors, was collected. This dataset, with its rich anatomical diversity and scanning parameters, was carefully selected to ensure comprehensive model training. Due to the imperfect registration, the inherent challenge of local structural misalignment of paired dataset may lead to suboptimal model performance. To address this limitation, we propose SynREG, a supervised learning framework. SynREG integrates a hybrid CNN-transformer architecture designed for generating high-fidelity sCT images and a registration network designed to correct local structural misalignment dynamically during training. An independent test set of 23 additional patients was used to evaluate the image quality, and the results were compared with those of several benchmark models (pix2pix, cycleGAN and SwinIR). Furthermore, the performance of an autosegmentation application was also assessed. Results: The proposed model disentangled sCT generation from anatomical correction, leading to a more rational optimization process. As a result, the model effectively suppressed noise and artifacts in multisite applications, significantly enhancing CBCT image quality. Specifically, the mean absolute error (MAE) of SynREG was reduced to 16.81 ± 8.42 HU, whereas the structural similarity index (SSIM) increased to 94.34 ± 2.85%, representing improvements over the raw CBCT data, which had the MAE of 26.74 ± 10.11 HU and the SSIM of 89.73 ± 3.46%. The enhanced image quality was particularly beneficial for organs with low contrast resolution, significantly increasing the accuracy of automatic segmentation in these regions. Notably, for the brainstem, the mean Dice similarity coefficient (DSC) increased from 0.61 to 0.89, and the MDA decreased from 3.72 mm to 0.98 mm, indicating a substantial improvement in segmentation accuracy and precision. Conclusions: SynREG can effectively alleviate the differences in residual anatomy between paired datasets and enhance the quality of CBCT images.
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Background: A variety of nutritional evaluation parameters has been documented as prognostic indicators in some malignancies. However, the prognostic significance of the controlling nutritional status (CONUT) score, as one of these nutritional indices, in patients with esophageal squamous cell carcinoma (ESCC) remains unclear and warrants investigation. Our study sought to elucidate the prognostic value of this nutritional index in ESCC patients who underwent neoadjuvant therapy followed by esophagectomy. Methods: This retrospective study encompassed 314 patients diagnosed with ESCC who underwent neoadjuvant therapy followed by esophagectomy at West China Hospital of Sichuan University between August 2016 and August 2021. CONUT scores were computed at two specific time points: prior to neoadjuvant therapy initiation and before surgery, utilizing serum albumin, total lymphocyte, and cholesterol levels of ESCC patients. Furthermore, the delta CONUT (ΔCONUT) score was derived by subtracting the preoperative CONUT score from the pretreatment CONUT score. The associations between CONUT scores and various survival outcomes were evaluated using Kaplan-Meier methods and Cox regression analysis. Results: Patients with a high preoperative CONUT score demonstrated a higher postoperative complication rate [odds ratio (OR) =2.009, 95% confidence interval (CI): 1.150-3.510, P=0.01] compared to those in the low CONUT group. Multivariate analysis revealed that a ΔCONUT score ≥0 served as an independent negative prognostic indicator for increased postoperative complications (OR =3.008, 95% CI: 1.509-5.999, P=0.002) and poorer overall survival [hazard ratio (HR) =2.388, 95% CI: 1.052-5.422, P=0.04] in ESCC patients who underwent neoadjuvant therapy combined with esophagectomy. Conclusions: A high preoperative CONUT score and a ΔCONUT score ≥0 were indicative of a poor prognostic nutritional status in ESCC patients who had undergone neoadjuvant therapy followed by esophagectomy.
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BACKGROUND: Currently, mediastinoscopy-assisted esophagectomy (MAE) and thoracoscope-assisted esophagectomy (TAE) represent two prevalent forms of minimally invasive esophagectomy extensively employed in the management of esophageal cancer (EC). The aim of this meta-analysis is to assess and compare these two surgical approaches concerning perioperative outcomes and long-term survival, offering valuable insights for refining surgical strategies and enhancing patient outcomes in this field. METHODS: Adhering to PRISMA guidelines, we systematically searched PubMed, Web of Science, Cochrane Library, Embase, and CNKI databases until March 1, 2024, for studies comparing MAE and TAE. Outcomes of interest included perioperative outcomes (intraoperative outcomes, postoperative recovery, postoperative complications) and survival rates. Statistical analyses were performed using RevMan 5.4, with heterogeneity dictating the use of fixed or random-effects models. RESULTS: Totally 21 relevant studies were finally included. MAE was associated with significantly shorter operation times ((MD=-59.58 min, 95% CI: -82.90, -36.26) and less intraoperative blood loss (MD=-68.34 mL, 95% CI: -130.45, -6.23). However, MAE resulted in fewer lymph nodes being dissected (MD=-3.50, 95% CI: -6.23, -0.78). Postoperative recovery was enhanced following MAE, as evidenced by reduced hospital stays and tube times. MAE significantly reduced pulmonary complications (OR=0.59, 95% CI: 0.44, 0.81) but increased the incidence of recurrent laryngeal nerve injury (OR=1.84, 95% CI: 1.30, 2.60). No significant differences were observed in anastomotic leakage, chylothorax, cardiac complications, wound infections, and gastric retention between MAE and TAE. The long-term survival outcomes showed no statistical difference (HR=1.05, 95% CI: 0.71-1.54). CONCLUSIONS: MAE offers advantages in reducing operation time, blood loss, and specific postoperative complications, particularly pulmonary complications, with a shorter recovery period compared to TAE. However, it poses a higher risk of recurrent laryngeal nerve injury and results in fewer lymph nodes being dissected. No difference in long-term survival was observed, indicating that both techniques have distinct benefits and limitations. These findings underscore the need for personalized surgical approaches in EC treatment, considering individual patient characteristics and tumor specifics.
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As a product of nonenzymatic glycation, glycated albumin (GA) is a promising serum marker for the short-term glycemic monitoring in patients with diabetes. On the basis of the boronate crosslinking (BCL)-enabled direct labeling of ferrocene (Fc) tags to the nonenzymatically glycated (NEG) sites, we report herein a novel aptamer-based ratiometric electrochemical (apt-REC) platform for the point-of-care (POC) assay of GA. This apt-REC platform is based on the recognition of GA proteins by the methylene blue (MB)-modified aptamer receptors and the labeling of the Fc tags to the NEG sites via the BCL. Using MB as the reference tag and Fc as the quantification tag, the ratio of the oxidation currents (i.e., IFc/IMB) can serve as the yardstick for the ratiometric assay of GA. Due to the presence of tens of the NEG sites, each GA protein can be labeled with tens of quantification tags, permitting the amplified assay in a simple, time-saving, and low-cost manner. The ratiometric signal exhibited a good linear response over the range from 0.1 to 100 µg/mL, with a detection limit of 45.5 ng/mL. In addition to the superior reproducibility and robustness, this apt-REC platform is highly selective (capable of discriminating GA against human serum albumin (HSA)) and applicable to GA assay in serum samples. Due to its low cost, high reproducibility and robustness, simple operation, and high sensitivity and selectivity, this apt-REC platform holds great promise in the POC assay of GA for diabetes management.
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Ácidos Borônicos , Técnicas Eletroquímicas , Albumina Sérica Glicada , Humanos , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Ácidos Borônicos/química , Reagentes de Ligações Cruzadas/química , Técnicas Eletroquímicas/métodos , Produtos Finais de Glicação Avançada/química , Limite de Detecção , Albumina Sérica/química , Albumina Sérica/análise , Albumina Sérica Humana/química , Albumina Sérica Humana/análiseRESUMO
This comprehensive review explores the development of food-grade selection markers in lactic acid bacteria and yeast; some of their strains are precisely defined as safe microorganisms and are crucial in the food industry. Lactic acid bacteria, known for their ability to ferment carbohydrates into lactic acid, provide essential nutrients and contribute to immune responses. With its strong fermentation capabilities and rich nutritional profile, yeast finds use in various food products. Genetic engineering in these microorganisms has grown rapidly, enabling the expression of enzymes and secondary products for food production. However, the focus is on ensuring safety, necessitating food-grade selection markers. Traditional antibiotic and heavy metal resistance selection markers pose environmental and health risks, prompting the search for safer alternatives. Complementary selection markers, such as sugar utilization markers, offer a promising solution. These markers use carbohydrates as carbon sources for growth and are associated with the natural metabolism of lactic acid bacteria and yeast. This review discusses the use of specific sugars, such as lactose, melibiose, sucrose, D-xylose, glucosamine, and N-acetylglucosamine, as selection markers, highlighting their advantages and limitations. In summary, this review underscores the importance of food-grade selection markers in genetic engineering and offers insights into their applications, benefits, and challenges, providing valuable information for researchers in the field of food microbiology and biotechnology.
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Lactobacillales , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Lactobacillales/genética , Antibacterianos , Biotecnologia , CarboidratosRESUMO
Esophageal cancer (EC) treatment via anti-angiogenic therapy faces challenges due to non-cytotoxicity and non-specific biodistribution of the anti-angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid-responsive release nanosystem (Bev-IR820@FeIII TA) that involves the conjugation of bevacizumab, an anti-angiogenic monoclonal antibody, with TA and Fe3+ to form a metal-phenolic network, followed by loading with the near-infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev-IR820@FeIII TA can be realized through a facile self-assembly process. The Bev-IR820@FeIII TA exhibits tumor-targeting capabilities and synergistic therapeutic effects, encompassing anti-angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev-IR820@FeIII TA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH-responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.
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Neoplasias Esofágicas , Ferroptose , Humanos , Terapia Fototérmica , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Compostos Férricos , Distribuição Tecidual , Neoplasias Esofágicas/tratamento farmacológicoRESUMO
The rapid quantification of therapeutic monoclonal antibodies (mAbs) is of great significance to their pharmacokinetics/pharmacodynamics (PK/PD) research and the personalized medication for disease treatment. Taking advantage of the direct decoration of tens of redox tags to the target of interest, we illustrate herein an amplification-free ratiometric electrochemical aptasensor for the point-of-care (POC) detection of trace amounts of therapeutic mAbs. The POC detection of therapeutic mAbs involved the use of the methylene blue (MB)-conjugated aptamer as the affinity element and the decoration of therapeutic mAbs with ferrocene (Fc) tags via the boronate crosslinking, in which the MB-derived peak current was used as the reference signal, and the peak current of the Fc tag was used as the output signal. As each therapeutic mAb carries tens of diol sites for the site-specific decoration of the Fc output tags, the boronate crosslinking enabled the amplification-free detection, which is cost-effective and quite simple in operation. In the presence of bevacizumab (BevMab) as the target, the resulting ratiometric signal (i.e., the IFc/IMB value) exhibited a good linear response over the range of 0.025-2.5 µg/mL, and the limit of detection (LOD) of the electrochemical aptasensor was 6.5 ng/mL. Results indicated that the aptamer-based affinity recognition endowed the detection of therapeutic mAbs with high selectivity, while the ratiometric readout exhibited satisfactory reproducibility and robustness. Moreover, the ratiometric electrochemical aptasensor is applicable to the detection of therapeutic mAbs in serum samples. Taking together, the amplification-free ratiometric electrochemical aptasensor holds great promise in the POC detection of therapeutic mAbs.
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Anticorpos Monoclonais , Tetranitrato de Pentaeritritol , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos Testes , Bevacizumab , Azul de Metileno , OligonucleotídeosRESUMO
BACKGROUND: An increasing number of cohort studies have indicated a correlation between lung diseases and esophageal cancer, but the exact causal relationship has not been definitively established. Therefore, the objective of this study is to assess the causal relationship between lung diseases and esophageal cancer. METHODS: Single-nucleotide polymorphisms (SNPs) related to lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF), along with outcomes data on esophageal cancer, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse-variance-weighted method. RESULTS: Totally, 81 SNPs related to asthma among 218,792 participants in GWAS. Based on the primary causal effects model using MR analyses with the inverse variance weighted (IVW) method, asthma was demonstrated a significantly related to the risk of esophageal cancer (OR 1.0006; 95% CI 1.0003-1.0010, p = 0.001), while COPD (OR 1.0306; 95% CI 0.9504-1.1176, p = 0.466), lung cancer (OR 1.0003, 95% CI 0.9998-1.0008, p = 0.305), as well as IPF (OR 0.9999, 95% CI 0.9998-1.0000, p = 0.147), showed no significant correlation with esophageal cancer. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between asthma and esophageal cancer. In contrast, esophageal cancer demonstrated no significant correlation with COPD, lung cancer, or IPF. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding esophageal cancer screening among patients with asthma.
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Asma , Neoplasias Esofágicas , Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Asma/genética , Neoplasias Esofágicas/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Human epidermal growth factor receptor-3 (HER-3) plays a key role in the growth and metastasis of cancer cells. The detection of HER-3 is very important for early screening and treatment of cancer. The AlGaN/GaN-based ion-sensitive heterostructure field effect transistor (ISHFET) is sensitive to surface charges. This makes it a promising candidate for the detection of HER-3. In this paper, we developed a biosensor for the detection of HER-3 with AlGaN/GaN-based ISHFET. The AlGaN/GaN-based ISHFET biosensor exhibits a sensitivity of 0.53 ± 0.04 mA/dec in 0.01 M phosphate buffer saline (1× PBS) (pH = 7.4) solution with 4% bovine serum albumin (BSA) at a source and drain voltage of 2 V. The detection limit is 2 ng/mL. A higher sensitivity (2.20 ± 0.15 mA/dec) can be achieved in 1× PBS buffer solution at a source and drain voltage of 2 V. The AlGaN/GaN-based ISHFET biosensor can be used for micro-liter (5 µL) solution measurements and the measurement can be performed after incubation of 5 min.
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OBJECTIVE: This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. METHODS: A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. RESULTS: The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. CONCLUSION: The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Procedimentos Cirúrgicos Robóticos , Marcadores Fiduciais , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/cirurgia , Incerteza , Planejamento da Radioterapia Assistida por ComputadorRESUMO
As the entering of bacterial endotoxin into blood can cause various life-threatening pathological conditions, the screening and detection of low-abundance endotoxin are of great importance to human health. Taking advantage of signal amplification by target-assisted electrochemically mediated atom transfer radical polymerization (teATRP), we illustrate herein a simple and cost-effective electrochemical aptasensor capable of detecting endotoxin with high sensitivity and selectivity. Specifically, the aptamer receptor was employed for the selective capture of endotoxin, of which the glycan chain was then decorated with ATRP initiators via covalent coupling between the diol sites and phenylboronic acid (PBA) group, followed by the recruitment of ferrocene signal reporters via the grafting of polymer chains through potentiostatic eATRP under ambient temperature. As the glycan chain of endotoxin can be decorated with hundreds of ATRP initiators while the further grafting of polymer chains through eATRP can recruit hundreds to thousands of signal reporters to each initiator-decorated site, the teATRP-based strategy allows for the dual amplification of the detection signal. This dually amplified electrochemical aptasensor has the ability to sensitively and selectively detect endotoxin at a concentration as low as 1.2 fg/mL, and its practical applicability has been further demonstrated using human serum samples. Owing to the simplicity, high efficiency, biocompatibility, and inexpensiveness of the teATRP-based amplification strategy, this electrochemical aptasensor holds great application potential in the sensitive and selective detection of low-abundance endotoxin and many other glycan chain-containing bio-targets.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Humanos , Limite de Detecção , Endotoxinas , Polímeros , Oligonucleotídeos , Técnicas EletroquímicasRESUMO
The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential negative factor in the survival of patients with malignant tumours. The aim of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and survival outcomes or postoperative complications in patients with oesophageal cancer (EC). Web of Science, Embase, Medline, and Cochrane Library databases were searched until 10 May 2022, using keywords: sarcopenia, oesophageal cancer, and prognosis. Studies investigating the prognostic value of sarcopenia on EC survival were included. Forest plots and summary effect models were used to show the result of this meta-analysis. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). A total of 1436 studies were identified from the initial search of four databases, and 41 studies were included for the final quantitative analysis. This meta-analysis revealed a significant association between sarcopenia and overall survival (OS) [hazard ratios (HR):1.68, 95% confidence interval (CI):1.54-1.83, P = 0.004, I2 = 41.7%] or disease-free survival (DFS) 1.97 (HR: 1.97, 95% CI: 1.44-2.69, P = 0.007, I2 = 61.9%) of EC patients. Subgroup analysis showed that sarcopenia remained a consistent negative predictor of survival when stratified by different treatment methods, populations, or sarcopenia measurements. Sarcopenia was also a risk factor for postoperative complications with a pooled odds ratio of 1.47 (95% CI: 1.21-1.77, P = 0.094, I2 = 32.7%). The NOS scores of all included studies were ≥6, and the quality of the evidence was relatively high. The results from the study suggested that sarcopenia was significantly associated with both survival outcomes and postoperative complications in EC patients. Sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with EC.
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Neoplasias Esofágicas , Sarcopenia , Humanos , Idoso , Prognóstico , Sarcopenia/complicações , Sarcopenia/diagnóstico , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Modelos de Riscos Proporcionais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
As lipopolysaccharide (LPS) is closely associated with sepsis and other life-threatening conditions, the point-of-care (POC) detection of LPS is of significant importance to human health. In this work, we illustrate an electrochemical aptasensor for the POC detection of low-abundance LPS by utilizing boronate affinity (BA) as a simple, efficient, and cost-effective amplification strategy. Briefly, the BA-amplified electrochemical aptasensing of LPS involves the tethering of the aptamer receptors and the BA-mediated direct decoration of LPS with redox signal tags. As the polysaccharide chain of LPS contains hundreds of cis-diol sites, the covalent crosslinking between the phenylboronic acid group and cis-diol sites can be harnessed for the site-specific decoration of each LPS with hundreds of redox signal tags, thereby enabling amplified detection. As it involves only a single-step operation (â¼15 min), the BA-mediated signal amplification holds the significant advantages of unrivaled simplicity, rapidness, and cost-effectiveness over the conventional nanomaterial- and enzyme-based strategies. The BA-amplified electrochemical aptasensor has been successfully applied to specifically detect LPS within 45 min, with a detection limit of 0.34 pg/mL. Moreover, the clinical utility has been validated based on LPS detection in complex serum samples. As a proof of concept, a portable device has been developed to showcase the potential applicability of the BA-amplified electrochemical LPS aptasensor in the POC testing. In view of its simplicity, rapidness, and cost-effectiveness, the BA-amplified electrochemical LPS aptasensor holds broad application prospects in the POC testing.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanoestruturas , Humanos , Lipopolissacarídeos , Técnicas Eletroquímicas , Limite de Detecção , OuroRESUMO
Esophageal cancer (EC) is a common malignant gastrointestinal (GI) cancer in adults. Although surgical technology combined with neoadjuvant chemoradiotherapy has advanced rapidly, patients with EC are often diagnosed at an advanced stage and the five-year survival rate remains unsatisfactory. The poor prognosis and high mortality in patients with EC indicate that effective and validated therapy is of great necessity. Recently, immunotherapy has been successfully used in the clinic as a novel therapy for treating solid tumors, bringing new hope to cancer patients. Several immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell therapy, and tumor vaccines, have achieved significant breakthroughs in EC treatment. However, the overall response rate (ORR) of immunotherapy in patients with EC is lower than 30%, and most patients initially treated with immunotherapy are likely to develop acquired resistance (AR) over time. Immunosuppression greatly weakens the durability and efficiency of immunotherapy. Because of the heterogeneity within the immune microenvironment and the highly disparate oncological characteristics in different EC individuals, the exact mechanism of immunotherapy resistance in EC remains elusive. In this review, we provide an overview of immunotherapy resistance in EC, mainly focusing on current immunotherapies and potential molecular mechanisms underlying immunosuppression and drug resistance in immunotherapy. Additionally, we discuss prospective biomarkers and novel methods for enhancing the effect of immunotherapy to provide a clear insight into EC immunotherapy.
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Vacinas Anticâncer , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Receptores de Antígenos Quiméricos , Biomarcadores , Neoplasias Esofágicas/terapia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Microambiente TumoralRESUMO
Traditional GaAs-based frequency multipliers still exhibit great challenges to meet the demand for solid-state high-power THz sources due to low breakdown voltage and heat dissipation of the Schottky barrier diode (SBD). In this study, a GaN SBD chain was fabricated with n-/n+-GaN structure. As a consequence, the breakdown voltage of 54.9 V at 1 µA and cut-off frequency of 587.5 GHz at zero bias were obtained. A 120 GHz frequency-doubler module based on the GaN SBD chain was designed and fabricated. When driven with 500 mW input power in a continuous wave, the output power of the frequency-doubler module was 15.1 mW at 120 GHz. Moreover, the experiments show that the frequency-doubler module can endure an input power of 2 W. In addition, it is worth noting that the SBD chain works well at an anode temperature of 337.2 °C.
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X-ray computed tomography (CT) has an important role in precision medicine. However, CT contrast agents with high efficiency and the ability to translate diagnostic accuracy into therapeutic intervention are scarce. Here, poly(diiododiacetylene) (PIDA), a conjugated polymer composed of only carbon and iodine atoms, is reported as an efficient CT contrast agent to bridge CT diagnostic imaging with therapeutic intervention. PIDA has a high iodine payload (>84 wt%), and the aggregation of nanofibrous PIDA can further amplify CT intensity and has improved geometrical and positional stability in vivo. Moreover, with a conjugated backbone, PIDA is in deep blue color, making it dually visible by both CT imaging and the naked eyes. The performance of PIDA in CT-guided preoperative planning and visualization-guided surgery is validated using orthotopic xenograft rat models. In addition, PIDA excels clinical fiducial markers of imaging-guided radiotherapy in efficiency and biocompatibility, and exhibits successful guidance of robotic radiotherapy on Beagles, demonstrating clinical potential to translate CT diagnosis accuracy into therapeutic intervention for precision medicine.
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Iodo , Animais , Carbono , Cães , Humanos , Imagens de Fantasmas , Polímeros , Ratos , Tomografia Computadorizada por Raios X/métodosRESUMO
In this work, the epitaxial semipolar (11-22) AlN was prepared on nonpolar m-sapphire substrate by combining sputtering and high-temperature annealing. According to our systematic measurements and analysis from XRD, Raman spectra, and AFM, the evolution of crystalline structure and morphology was investigated upon increasing AlN thickness and annealing duration. The annealing operation intensively resets the lattice and improves the crystalline quality. By varying the film thickness, the contribution from the AlN-sapphire interface on crystalline quality and lattice parameters during the annealing process was investigated, and its contribution was found to be not so obvious when the thickness increased from 300 nm to 1000 nm. When the annealing was performed under durations from 1 to 5 h, the crystalline quality was found unchanged; meanwhile, the evolution of morphology was pronounced, and it means the crystalline reorganization happens prior to morphology reset. Finally, the annealing treatment enabled a zig-zag morphology on the AlN template along the sapphire [0001] direction in the plane, which potentially affects the subsequent device epitaxy process. Therefore, our results act as important experience for the semipolar nitride semiconductor laser device preparation, particularly for the epitaxy of microcavity structure through providing the crystalline evolution.
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Programmed cell death 1 (PD1) inhibitors have shown promising treatment effects in advanced gastric cancer, the beneficiary population not definite. This study aimed to construct an individualized radiomics model to predict the treatment benefits of PD-1 inhibitors in gastric cancer. Patients with advanced gastric cancer treated with PD-1 inhibitors were randomly divided into a training set (n = 58) and a validation set (n = 29). CT imaging data were extracted from medical records, and an individual radiomics nomogram was generated based on the imaging features and clinicopathological risk factors. Discrimination performance was evaluated by Harrell's c-index and receiver operator characteristic (ROC) curve analyses. The areas under the ROC curves (AUCs) were analyzed to predict anti-PD-1 efficacy and survival. We found that the radiomics nomogram could predict the response of gastric cancer to anti-PD-1 treatment. The AUC was 0.865 with a 95% CI of 0.812-0.828 in the training set, while the AUC was 0.778 with a 95% CI of 0.732-0.776 in the validation set. The diagnostic performance of the radiomics was significantly higher than that of the clinical factors (p < 0.01). Patients with a low risk of disease progression discriminated by the radiomics nomogram had longer progression-free survival than those with a high risk (6.5 vs. 3.2 months, HR 1.99, 95% CI: 1.19-3.31, p = 0.009). The radiomics nomogram based on CT imaging features and clinical risk factors could predict the treatment benefits of PD-1 inhibitors in advanced gastric cancer, enabling it to guide decision-making regarding clinical treatment.
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Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Nomogramas , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodosRESUMO
Virtual reality (VR) presents opportunities for innovative patient educational methods. This study used a combination of subjective questionnaires and objective physiological measures to investigate the impact of a VR radiotherapy (RT) educational system on patients' understanding and anxiety prior to commencing RT. Sixty patients were randomized to control (n = 30) and intervention (n = 30) groups prior to initiating RT. The control group received the standard nursing care process. The intervention group additionally participated in a detailed introduction to RT positioning, procedures, treatments, and other RT-related information via VR education. All patients completed a data collection from pre- and postintervention, which included questions on RT comprehension, anxiety-related scales, and objective physiological data reflecting the patient's psychological state, such as blood pressure, heart rate, and respiration. Both groups had high anxiety levels before the intervention, and there was no significant difference between the questionnaire and physiological data of the two groups. Following the intervention, anxiety scores (state-trait anxiety scale and visual analog scale) of the intervention group decreased significantly compared with those of the control group, and there was a significant decrease in systolic blood pressure (p < 0.05) and increase in cognitive score (p < 0.05). This study reports the positive impact of a virtual reality radiotherapy (VRRT) patient educational system on increasing patient RT comprehension and reducing anxiety. Further work is needed to improve the acceptability of the system to patients and to explore further the impact of VR education on patients' psychological and physical needs.