ABSTRACT
Existing issues with bio-based adhesives, such as complex preparation processes, high energy consumption, and production costs, still need to be addressed. In our study, APTES was grafted onto microcrystalline cellulose (MCC) to generate active aminated cellulose, and then reacted with the epoxide group in glycerol triglycidyl ether (GTE) through a swelling strategy under alkaline solvent, forming a network structure via covalent cross-linking. The adhesive exhibits superior bonding performance and water-resistant property in the bonding strength test of poplar plywood, with a dry shear strength of 2.40 MPa, a wet shear strength of 2.16 MPa after soaking in 63 °C hot water, and a wet shear strength of 1.79 MPa after soaking in boiling water. In terms of cost calculation, the theoretical production cost of AC-GTE adhesive is calculated to be 5303.7 RMB per ton, which is comparable to that of phenol-formaldehyde (PF) resin and other petrochemical-based adhesives, and significantly lower than that of isocyanate-based adhesives. These research results can provide a practical example for producing high-efficiency, aldehyde-free, and low-cost bio-based adhesives.
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Optical chaos communication is a promising secure transmission technique because of the advantages of high speed and compatibility with existing fiber-optic systems. The deterioration of chaotic synchronization quality caused by fiber optic transmission impairments affects the quality of recovery of information, especially high-order modulated signals. Here, we demonstrate that the use of a convolutional neural network (CNN) with a bidirectional long short-term memory (LSTM) layer can reduce the decryption BER in an optical chaos communication system based on common-signal-induced semiconductor laser synchronization. The performance of a neural network is investigated as a function of network parameters and chaos synchronization coefficient. Experimental results show that the BER of 16-ary quadrature-amplitude-modulation (16QAM) signal after 100-km fiber transmission is decreased from 3.05 × 10-2 to below the soft-decision forward-error-correction (SD-FEC) threshold of 2.0 × 10-2.
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Anoikis tolerance is an important biological process of tumor colonization and metastasis outside the primary tumor. Recent research has progressively elucidated the function and underlying mechanisms of anoikis in the metastasis of various solid tumors. Nevertheless, the specific mechanisms of anoikis in bladder cancer and its consequent effects on the tumor immune microenvironment remain ambiguous. In this study, we developed an anoikis score based on five genes (ETV7, NGF, SCD, LAMC1, and CASP6) and categorized subjects into high and low-risk groups using the median score from the TCGA database. Our findings indicate that SCD enhances the proliferation of bladder cancer cells in vitro. Furthermore, integrating the anoikis score with clinicopathological features to construct a prognostic nomogram demonstrated precision in assessing patient outcomes. Immune cell analysis revealed elevated infiltration levels of Treg cells and M2 macrophages in the high anoikis score group, whereas CD8+ T cell levels were reduced. This study highlights the importance of anoikis score in predicting patient prognosis, immune cell infiltration, and drug response, which may provide a treatment modality worth exploring in depth for the study of bladder cancer.
ABSTRACT
Aimed at energy conservation and water saving for the lab, we have designed and constructed one kind of lab-scale small recirculating device of cooling water utilizing a water recirculator coupled to a solar energy system via a self-made multifunctional voltage regulator, which is equipped with an active heat radiator and powered by a solar energy system. It can provide cooling water for 1-3 sets of ordinary refluxing setups in series without additional consumption of water and electricity. The temperature difference between the water in the bucket and the environment is less than 4 °C for eight common solvents in single refluxing set-up or three combined refluxing setups with different solvents in series. In the performance assessment experiments for the refluxing of eight common solvents with different boiling point, the largest solvent loss is less than 6% if the condenser is open to the air in the refluxing time of 8 h, but none obvious solvent loss are found if the condensers were equipped with an oil bubbler. Control experiments indicates that the preparation of bromoethane/ethyl acetate/propyl hexanoate using our water recirculator can achieve almost unanimous yields in relative to those reactions using tap water as cooling water.
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OBJECTIVES: Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma. Dual-energy computed tomography (DECT) is a highly sensitive technique that can determine the iodine concentration (IC) in tumour and provide an indirect evaluation of internal microcirculatory perfusion. This study aimed to assess whether the combination of DECT with laboratory data can improve preoperative MVI prediction. METHODS: This retrospective study enrolled 119 patients who underwent DECT liver angiography at 2 medical centres preoperatively. To compare DECT parameters and laboratory findings between MVI-negative and MVI-positive groups, Mann-Whitney U test was used. Additionally, principal component analysis (PCA) was conducted to determine fundamental components. Mann-Whitney U test was applied to determine whether the principal component (PC) scores varied across MVI groups. Finally, a general linear classifier was used to assess the classification ability of each PC score. RESULTS: Significant differences were noted (P < .05) in alpha-fetoprotein (AFP) level, normalized arterial phase IC, and normalized portal phase IC between the MVI groups in the primary and validation datasets. The PC1-PC4 accounted for 67.9% of the variance in the primary dataset, with loadings of 24.1%, 16%, 15.4%, and 12.4%, respectively. In both primary and validation datasets, PC3 and PC4 were significantly different across MVI groups, with area under the curve values of 0.8410 and 0.8373, respectively. CONCLUSIONS: The recombination of DECT IC and laboratory features based on varying factor loadings can well predict MVI preoperatively. ADVANCES IN KNOWLEDGE: Utilizing PCA, the amalgamation of DECT IC and laboratory features, considering diverse factor loadings, showed substantial promise in accurately classifying MVI. There have been limited endeavours to establish such a combination, offering a novel paradigm for comprehending data in related research endeavours.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Neoplasm Invasiveness , Tomography, X-Ray Computed , Humans , Male , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/blood supply , Female , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/blood supply , Retrospective Studies , Middle Aged , Tomography, X-Ray Computed/methods , Aged , Contrast Media , Iodine , Microvessels/diagnostic imaging , Microvessels/pathology , Adult , alpha-Fetoproteins/analysis , alpha-Fetoproteins/metabolismABSTRACT
Eucommia ulmoides is a traditional Chinese herbal medicine, with pharmacological effects such as lowering blood pressure and enhancing immune function. The effects of dietary Eucommia ulmoides polysaccharide (EUP) on immune function and meat quality were studied in Songliao Black Pigs. Blood lymphocyte counts and percentage, concentrations of serum total protein and of albumin increased, whereas those of urea nitrogen and triglyceride decreased. White blood cell and lymphocyte counts, and serum IgA, IgE, IgG2 a and IFN-γ increased. Average daily weight gain, slaughter weight, lean meat rate and cooked meat rate increased, whereas pH24, feed-weight ratio, fat rate, yellowness (b#) and centrifugal dehydration rate decreased. Transcriptome sequencing of longissimus dorsi muscle detected 32 differentially expressed genes (DEGs), of which 26 were up-regulated and 6 down-regulated. A total of 19 genes were differentially expressed in the four groups, 18 of which were up-regulated. The DEGs included ADAMTS4, PER1, STAC, SERPINE1, FASN, THRSP, SP7 and KRT80 and the protein interaction network showed 20 up-regulated nodes, three down-regulated nodes and 14 DEGs. GO functional annotation and enrichment analysis showed that 34 items were significantly enriched, including transferase activity, actin binding, acetyl coenzyme A, acyl coenzyme A metabolism, adipose tissue development and acyl glycerol homeostasis. KEGG pathway analysis showed that the AMPK and PPAR signaling pathways were enriched. Dietary Eucommia polysaccharide enhanced immune function in Songliao Black Pigs, improved growth and carcass performance, increased the expression of genes related to meat quality traits and improved meat quality.
Subject(s)
Eucommiaceae , Polysaccharides , Animals , Polysaccharides/pharmacology , Eucommiaceae/chemistry , Swine , Animal Feed/analysis , Meat/analysis , Transcriptome , Dietary Supplements , Pork Meat/analysis , Gene Expression Profiling , Diet/veterinaryABSTRACT
We proposed and verified a scheme of chaos synchronization for integrated five-section semiconductor lasers with matching parameters. The simulation results demonstrated that the integrated five-section semiconductor laser could generate a chaotic signal within a large parameter range of the driving currents of five sections. Subsequently, chaos synchronization between two integrated five-section semiconductor lasers with matched parameters was realized by using a common noise signal as a driver. Moreover, it was found that the synchronization was sensitive to the current mismatch in all five sections, indicating that the driving currents of the five sections could be used as keys of chaotic optical communication. Therefore, this synchronization scheme provides a candidate to increase the dimension of key space and enhances the security of the system.
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Current therapeutic options for renal cell carcinoma (RCC) are very limited, which is largely due to inadequate comprehension of molecular pathological mechanisms as well as RCC's resistance to chemotherapy. Dual-specificity phosphatase 6 (DUSP6) has been associated with numerous human diseases. However, its role in RCC is not well understood. Here, we show that diminished DUSP6 expression is linked to RCC progression and unfavorable prognosis. Mechanistically, DUSP6 serves as a tumor suppressor in RCC by intervening the TAF10 and BSCL2 via the ERK-AKT pathway. Further, DUSP6 is also transcriptionally regulated by HNF-4a. Moreover, docking experiments have indicated that DUSP6 expression is enhanced when bound by Calcium saccharate, which also inhibits RCC cell proliferation, metabolic rewiring, and sunitinib resistance. In conclusion, our study identifies Calcium saccharate as a prospective pharmacological therapeutic approach for RCC.
Subject(s)
Antineoplastic Agents , Carcinoma, Renal Cell , Dual Specificity Phosphatase 6 , Glycolysis , Kidney Neoplasms , Proto-Oncogene Proteins c-akt , Sunitinib , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Sunitinib/pharmacology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Glycolysis/drug effects , Glycolysis/physiology , Cell Line, Tumor , Proto-Oncogene Proteins c-akt/metabolism , Animals , Dual Specificity Phosphatase 6/metabolism , Dual Specificity Phosphatase 6/genetics , Antineoplastic Agents/pharmacology , Mice , Mice, Nude , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , MaleABSTRACT
Adenosine (Ado) is significantly elevated in the tumor microenvironment (TME) compared to normal tissues. It binds to adenosine receptors (AdoRs), suppressing tumor antigen presentation and immune cell activation, thereby inhibiting tumor adaptive immunity. Ado downregulates major histocompatibility complex II (MHC II) and co-stimulatory factors on dendritic cells (DCs) and macrophages, inhibiting antigen presentation. It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor (TCR) binding and signal transduction. Ado also inhibits chemokine secretion and KCa3.1 channel activity, impeding effector T cell trafficking and infiltration into the tumor site. Furthermore, Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion, upregulating immune checkpoint proteins, and enhancing immune-suppressive cell activity. Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies. Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway. Therefore, this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity, as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.
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OBJECTIVE: Personalized precision medicine can be facilitated by clinically available preoperative microvascular invasion (MVI) prediction models that are reliable and postoperative MVI pathological grade-related recurrence prediction models that are accurate. In this study, we aimed to compare different mathematical models to derive the best preoperative prediction and postoperative recurrence prediction models for MVI. METHODS: A total of 143 patients with hepatocellular carcinoma (HCC) whose clinical, laboratory, imaging, and pathological data were available were included in the analysis. Logistic regression, Cox proportional hazards regression, LASSO regression with 10-fold cross-validation, stepwise regression, and random forest methods were used for variable screening and predictive modeling. The accuracy and validity of seven preoperative MVI prediction models and five postoperative recurrence prediction models were compared in terms of C-index, net reclassification improvement, and integrated discrimination improvement. RESULTS: Multivariate logistic regression analysis revealed that a preoperative nomogram model with the variables cirrhosis diagnosis, alpha-fetoprotein > 400, and diameter, shape, and number of lesions can predict MVI in patients with HCC reliably. Postoperatively, a nomogram model with MVI grade, number of lesions, capsule involvement status, macrovascular invasion, and shape as the variables was selected after LASSO regression and 10-fold cross-validation analysis to accurately predict the prognosis for different MVI grades. The number and shape of the lesions were the most common predictors of MVI preoperatively and recurrence postoperatively. CONCLUSIONS: Our study identified the best statistical approach for the prediction of preoperative MVI as well as postoperative recurrence in patients with HCC based on clinical, imaging, and laboratory tests results. This could expedite preoperative treatment decisions and facilitate postoperative management.
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Purpose: The main aim of this study is to analyze the relationship between body composition indices and metabolic unhealthy phenotypes in young and middle-aged obese patients and to assess their joint predictive ability. Patients and Methods: A cross-sectional study method was used to select 207 patients who were proposed to undergo weight loss surgery for morbid obesity from March to November 2022. Total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), liver fat content (LFC), cross-sectional area (CSAmuscle), and intermuscular adipose tissue (CSAIMAT) of paraspinal muscles were measured using quantitative computed tomography. Participants were categorized into two groups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The receiver operating characteristic curve comprised body composition variables that correlated with MUO, and the area under the curve (AUC) was calculated to compare their prediction capacity for MUO. Results: There were 71 patients with MHO (34.3%) and 136 patients with MUO (65.7%). The VAT, VAT/TAT ratio, LFC, and CSAmuscle was higher in MUO patients than in MHO (all P < 0.001), and SAT was lower than in MHO (P = 0.008). And all of these metrics were correlated with MUO (all P < 0.05). Inclusion of these body composition metrics in the ROC analysis showed that the AUC values for SAT, VAT, VAT/TAT ratio, LFC and CSAmuscle were 0.615, 0.663, 0.727, 0.694, 0.671, respectively, and the combination of the VAT/TAT ratio and the LFC had the ability to predict MUO best (AUC=0.746, P = 0.025). Conclusion: The combined use of VAT/TAT ratio and LFC is superior to the use of these two metrics alone in terms of their ability to predict the MUO, providing a more accurate approach to the management and prevention of obesity-related metabolic risk.
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Diminished or lost Major Histocompatibility Complex class I (MHC-I) expression is frequently observed in tumors, which obstructs the immune recognition of tumor cells by cytotoxic T cells. Restoring MHC-I expression by promoting its transcription and improving protein stability have been promising strategies for reestablishing anti-tumor immune responses. Here, through cell-based screening models, we found that cediranib significantly upregulated MHC-I expression in tumor cells. This finding was confirmed in various non-small cell lung cancer (NSCLC) cell lines and primary patient-derived lung cancer cells. Furthermore, we discovered cediranib achieved MHC-I upregulation through transcriptional regulation. interferon regulatory factor 1 (IRF-1) was required for cediranib induced MHC-I transcription and the absence of IRF-1 eliminated this effect. Continuing our research, we found cediranib triggered STAT1 phosphorylation and promoted IRF-1 transcription subsequently, thus enhancing downstream MHC-I transcription. In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8+ T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Indoles , Lung Neoplasms , Humans , Interferon Regulatory Factor-1/genetics , Lung Neoplasms/drug therapy , Quinazolines/pharmacologyABSTRACT
The study aimed to explore the protective effects of Inonotus obliquus polysaccharide (IOP) on Neospora caninum (N. caninum) infection. Our data showed that the survival rate of the mice was the highest and the survival time was the longest when the IOP was 2 mg/10 g. In agreement with these observations, IOP alleviated the pathological damage in the various organs and tissues of the mice. Compared with that in the Neosporidium infection model group, the content of N. caninum in the heart, liver, spleen, lung, kidney and brain, determined through HE staining, was significantly lower. In addition, IOP inhibited the levels of immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2a) from the 21st to 42nd day of the administration group, whereas the levels of interleukin-12 (IL-12) and serum tumor necrosis factor alpha (TNF-α) were down-regulated at 7 d - 42 d. The production of CD4+ T lymphocytes was promoted, the number of CD8+ T lymphocytes were significantly lower and the CD4+/CD8+ ratio was significantly elevated. Furthermore, IOP effectively balanced the levels of hormones including gonadotropin-releasing hormone (GnRH), luteotropic hormone (LH) and testosterone (T) in male mice, and progesterone (PROG), estradiol (E2) and prolactin (PRL) in female mice. These findings demonstrate that IOP exerts protective effects against pathological damage caused by N. caninum infection in mice, and improve the immune function of the organism and regulate the secretion balance of sex hormones.
Subject(s)
Coccidiosis , Inonotus , Neospora , Female , Male , Animals , Mice , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Luteinizing Hormone , Coccidiosis/drug therapy , Coccidiosis/pathology , ImmunoglobulinsABSTRACT
OBJECTIVE: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). MATERIALS AND METHODS: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. RESULTS: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87-13.40]), IVHG (3.64 [2.15-6.24]), and RHE (7.90 [4.93-12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52-0.66]), IVHG (0.72 [0.64-0.81]), and RHE (0.61 [0.54-0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36-15.30] and 10.10 [7.10-14.60], respectively, for the blend sign and 2.75 [1.64-4.67] and 2.62 [1.60-4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. CONCLUSION: Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.
Subject(s)
Cerebral Hemorrhage , Tomography, X-Ray Computed , Humans , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/complications , Tomography, X-Ray Computed/methods , Predictive Value of Tests , Hematoma/diagnostic imaging , Logistic Models , Retrospective StudiesABSTRACT
BACKGROUND: Hematoma expansion (HE) is common in patients with intracerebral hemorrhage (ICH) and associated with a worse outcome. Imaging makers and shorter time from symptom onset are both associated with HE, but prognostic scores based on these parameters individually have not been satisfactory. We hypothesized that a score including both imaging markers of expansion, and time of onset, would improve prediction. METHODS: Patients with supratentorial ICH within 6 h after onset were consecutively recruited from six centers between January 2018 and August 2022. Three markers were used: hypodensities, the blend sign, and the island sign. We first defined frequency of imaging markers (FIM) as the relationship between the number of imaging markers and onset-to-CT time (OCT). The time-adjusted FIM was defined as the ratio of the number of imaging markers to the onset-to-initial imaging time. Multivariate analysis was performed to determine the relationship between FIM and HE. Receiver operating curve analysis was used to identify potential threshold values of FIM that optimally predict HE. In addition, the sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and the area under the curve (AUC) of the optimal cut-off in predicting HE were calculated. RESULTS: In total, 1488 patients were eligible for inclusion, of whom 418 had incident HE. Multivariate analysis showed that age, male sex, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, and FIM were independent predictors of HE (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.97-0.99; OR = 1.73, 95% CI = 1.28-2.35; OR = 0.87, 95% CI = 0.83-0.92; OR = 0.42, 95% CI = 0.28-0.62; OR = 7.82, 95% CI = 5.86-10.42, respectively). The optimal cut-off point for FIM in predicting HE was 0.63, with sensitivity, specificity, PPV, NPV, and AUC values of 0.69, 0.89, 0.71, 0.88, and 0.83, respectively. CONCLUSION: The FIM adjusted for time since symptom onset is a significant predictor of HE. Its use may allow improved prediction of those patients with ICH who develop HE, and the score may be clinically applicable in the management of patients with ICH.
Subject(s)
Stroke , Humans , Male , Stroke/complications , Cerebral Hemorrhage/complications , Hematoma/diagnostic imaging , Hematoma/complications , Tomography, X-Ray Computed , Computed Tomography Angiography , Retrospective StudiesABSTRACT
OBJECTIVES: To retrospectively evaluate the association between the presence of collateral vessels and grade of clear cell renal cell carcinoma (ccRCC) and whether the presence of collateral vessels could serve as a predictor to differentiate high- and low-grade ccRCC. MATERIALS AND METHODS: From May 2018 to September 2022, a total of 160 ccRCC patients with pathological diagnosis were enrolled in this study. Patients were divided into a high-grade group and a low-grade group according to World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system. The significant variables were extracted based on the univariate analyses using Student t test, Mann-Whitney U test, Chi-square test or Fisher's exact test. Multivariate logistic regression analyses were performed to determine independent factors among extracted variables. We calculated the sensitivity, specificity and their 95% confidence intervals (CI) of collateral vessels for predicting high WHO/ISUP grade to quantify its predictive performance. Furthermore, to investigate the additional predictive contribution of collateral vessels, a primary model and a control model were constructed to predict WHO/ISUP grade. The primary model included all extracted significant variables and the control model included significant variables except collateral vessels. RESULTS: The proportion of ccRCC patients with collateral vessels was significantly larger in high-grade ccRCC than those in low-grade ccRCC (87.5 % vs. 26.8 %, P < 0.001). Multivariate logistic regression analyses showed that the presence of collateral vessels was an independent predictor for high WHO/ISUP grade (P < 0.001). The sensitivity and specificity of the presence of collateral vessels for differentiating high- and low-grade ccRCC were 87.5 % (95 % CI 0.753-0.941) and 73.2 % (95 % CI 0.643-0.806) respectively. Including collateral vessels in predictive model improves predictive performance for WHO/ISUP grade, increasing the area under the curve (AUC) value from 0.889 to 0.914. CONCLUSION: The presence of collateral vessels has high sensitivity and specificity for differentiating high- and low-grade ccRCC and can improve the predictive performance for high WHO/ISUP grade.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/surgery , Retrospective Studies , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Tomography, X-Ray Computed/methods , Sensitivity and Specificity , Neoplasm GradingABSTRACT
Common-signal-induced laser synchronization promoted a promising paradigm of high-speed physical key distribution. Constant-amplitude and random-phase (CARP) light was proposed as the common drive signal to enhance security by reducing the correlation between the drive and the laser response in intensity. However, the correlation in light phase is not examined. Here, we numerically reveal that the correlation coefficient of the CARP light phase and the response laser intensity (denoted as CCR-φD) can reach a value close to 0.6. Effects of parameters including optical frequency detuning, and modulation depth and noise bandwidth and transparency carrier density for CARP light generation are investigated in detail. By optimizing the optical frequency, modulation depth, and noise bandwidth, respectively, CCR-φD can be reduced to 0.32, 0.18, and 0.10. In the meantime, CCR-φD can be further reduced through secondary optimizing of parameters. CCR-φD can be further reduced by increasing transparent carrier density provided response laser synchronization is achieved. This work gives a new insight about the laser synchronization induced by common CARP light, and also contributes a suggestion of security improvement for physical key distribution based on laser synchronization.
ABSTRACT
Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex â ¡ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.