The combination of chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT) based on a single nanosystem is highly desirable for cancer treatment. In this study, we developed a ...versatile Pt(IV) prodrug-based nanodrug, PVPt@Cy NPs, to realize synchronous chemotherapy, PDT and PTT and integrate cancer treatment with bioimaging. To construct PVPt@Cy NPs, the amphiphilic Pt(IV)-based polymeric prodrug PVPt was synthesized by a facile one-pot coupling reaction, and then it was used to encapsulate an optotheranostic agent (HOCyOH, Cy) via hydrophobic interaction-induced self-assembly. These NPs would disaggregate under acidic, reductive conditions and NIR irradiation, which are accompanied by photothermal conversion and reactive oxygen species (ROS) generation. Moreover, the PVPt@Cy NPs exhibited an enhanced in vitro anticancer efficiency with 808-nm light irradiation. Furthermore, the PVPt@Cy NPs showed strong NIR fluorescence and photothermal imaging in H22 tumor-bearing mice, allowing the detection of the tumor site and monitoring of the drug biodistribution. Therefore, PVPt@Cy NPs displayed an enormous potential in combined chemo-phototherapy.
Game theory is a powerful tool in modeling strategic interaction among rational players. However, as practical problems become more complex, uncertainty inevitably appears in the game. Due to the ...advantages of probabilistic linguistic term sets (PLTSs) in comprehensively and flexibly portraying uncertainty, fuzziness and hesitancy, this paper uses PLTSs to express players’ payoff values, and aims to develop an integrated method based on fuzzy envelope and prospect theory (PT) under a probabilistic linguistic environment for solving matrix games. In this method, an improved probabilistic ordered weighted averaging (POWA) operator is defined. Then, a novel trapezoidal fuzzy envelope for PLTSs is proposed and some related theorems are analyzed. Next, based on the defined cosine distance measure for PLTSs, the players’ psychological behavior in the game is considered by establishing the prospect value function. Besides, the applicability and practicability of the proposed method is verified with an example from the development strategy of Sanjiangyuan National Nature Reserve (SNNR) in China. Finally, some comparative analyses are carried out to illustrate the superiority of the proposed method. In order to improve the application of this proposed method, a decision support system (DSS) based on it is designed.
HVTN 505 is a preventative vaccine efficacy trial testing DNA followed by recombinant adenovirus serotype 5 (rAd5) in circumcised, Ad5-seronegative men and transgendered persons who have sex with men ...in the United States. Identified immune correlates of lower HIV-1 risk and a virus sieve analysis revealed that, despite lacking overall efficacy, vaccine-elicited responses exerted pressure on infecting HIV-1 viruses. To interrogate the mechanism of the antibody correlate of HIV-1 risk, we examined antigen-specific antibody recruitment of Fcγ receptors (FcγRs), antibody-dependent cellular phagocytosis (ADCP), and the role of anti-envelope (anti-Env) IgG3. In a prespecified immune correlates analysis, antibody-dependent monocyte phagocytosis and antibody binding to FcγRIIa correlated with decreased HIV-1 risk. Follow-up analyses revealed that anti-Env IgG3 breadth correlated with reduced HIV-1 risk, anti-Env IgA negatively modified infection risk by Fc effector functions, and that vaccine recipients with a specific FcγRIIa single-nucleotide polymorphism locus had a stronger correlation with decreased HIV-1 risk when ADCP, Env-FcγRIIa, and IgG3 binding were high. Additionally, FcγRIIa engagement correlated with decreased viral load setpoint in vaccine recipients who acquired HIV-1. These data support a role for vaccine-elicited anti-HIV-1 Env IgG3, antibody engagement of FcRs, and phagocytosis as potential mechanisms for HIV-1 prevention.
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is easily neglected in the non-obese population. TyG index (triglyceride glucose Index) and TG/HDL-c (triglyceride to high-density ...lipoprotein cholesterol) are new indicators to evaluate insulin resistance (IR). Fibroscan is a non-invasive way to assess hepatic steatosis by control attenuation parameters (CAP) and fibrosis by liver stiffness measurement (LSM).The purpose of this study was to explore the correlation of TyG and its combination with obesity indicators TyG-waist circumference (WC), TyG-body mass index (BMI) and TG/HDL-c with CAP and LSM.
Method
One thousand seven hundred seventy-six adults (age ≥ 20 years, BMI < 30 kg/m2) in the National Health and Nutrition Examination Survey (NHANES) 2017–2018 were included. The correlations of CAP and LSM to the indexes were assessed by generalized linear models.. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic capability of the indicators on NAFLD and liver stiffness.
Results
Survey-weighted percentage of NAFLD in non-obese was 38.6%. In the fully adjusted models, there were positive associations of TyG, TyG-BMI, TyG-WC and TG/HDL-c to CAP, with the βs of 24.810, 0.704, 0.29 and 2.983 (all
p
< 0.05), respectively. There were positive associations of TyG, TyG-BMI, TyG-WC, and TG/HDL-c to NAFLD, with ORs of 3.387, 1.03, 1.010 and 1.281 ((all
p
< 0.05)).The positive association was detected for TG/HDL-c and TyG-WC and LSM with βs of 0.057 and 0.004(
p
= 0.021 and
p
= 0.003).TyG-WC were positively associated with liver stiffness with OR of 1.006(95%CI = 1.002, 1.012). Furthermore, the TyG-WC had the strongest diagnostic capability (ROC = 0.806; 95%CI: 0.785–0.826) on NAFLD in non-obese participants, with a specificity of 0.737 and sensitivity of 0.746.
Conclusion
In US non-obese population, the TyG, TyG-BMI, TyG-WC, and TG/HDL-c are positively correlated with CAP and NAFLD. TyG-WC has clinical importance in identifying NAFLD in the non-obese population.
Abstract
Background
Adiposity evaluated by body mass index (BMI) is associated with glycometabolism. The aim of the investigation was to explore the correlation of visceral fat area (VFA), body fat ...percentage (BFP), BMI and waist circumference (WC) with type 2 diabetes mellitus (T2DM) and pre-diabetes.
Methods
A total of 18,458 participates underwent physical examination in Nanjing Drum Tower Hospital from January 2018 to April 2022 was included in this study. Data were collected retrospectively. Regression analysis was used to evaluate the relationship of VFA, BFP, WC and BMI with diabetes status, fasting blood glucose (FBG) and glycohemoglobin (HbA1c).
Results
After fully adjusted for multiple covariates, VFA, BFP, WC and BMI in T2DM and pre-diabetes group exceeded compared with normal group. FBG was positively correlated with VFA, BFP, WC and BMI with βs of 2.221,0.306,0.606 and 0.175(
p
< 0.001). HbA1c was also positively correlated with the four indexes with βs of 2.645, 0.328, 0.685 and 0.255(
p
< 0.001). Subgroup analysis shown that FBG and HbA1c were positively correlated with VFA, BFP, BMI and WC in normal and pre-diabetes group (
p
< 0.001). FBG was negatively correlated with BMI in T2DM group (
p
= 0.023). In T2DM, there were non-linear relationships of HbA1c with VFA, BFP, WC and BMI with the inflection points for about 7%. Before the inflection point, HbA1c was positively correlated with obesity-related indicators, and it was reversed after the inflection point. In the individuals with excessive VFA and normal BMI, the risk for glycometabolism disorder exceed compared with normal VFA and normal BMI. Every per-standard deviation increasing in VFA, BFP, WC and BMI, the corresponding risk increasing of glycometabolism disorder was 16.4, 14.6, 22.6 and 22.2%.
Conclusion
The study demonstrated that in adults with T2DM or prediabetes, the VFA, BFP, WC and BMI were higher than with normal glycometabolism. In pre-diabetes and normal population, there were positive correlations of HbA1c and FBG with obesity-related indicators. In T2DM with poor glycemic control (HbA1c > 7%), there might be a trend of fat loss. VFA could negatively affect glycometabolism independently from BMI. The optimum to evaluate the risk of glycometabolism disorder was WC.
The addition of plasmid cytokine adjuvants, electroporation, and live attenuated viral vectors may further optimize immune responses to DNA vaccines in heterologous prime-boost combinations. The ...objective of this study was to test the safety and tolerability of a novel prime-boost vaccine regimen incorporating these strategies with different doses of IL-12 plasmid DNA adjuvant.
In a phase 1 study, 88 participants received an HIV-1 multiantigen (gag/pol, env, nef/tat/vif) DNA vaccine (HIV-MAG, 3000 μg) co-administered with IL-12 plasmid DNA adjuvant at 0, 250, 1000, or 1500 μg (N = 22/group) given intramuscularly with electroporation (Ichor TriGrid™ Delivery System device) at 0, 1 and 3 months; followed by attenuated recombinant vesicular stomatitis virus, serotype Indiana, expressing HIV-1 Gag (VSV-Gag), 3.4 ⊆ 107 plaque-forming units (PFU), at 6 months; 12 others received placebo. Injections were in both deltoids at each timepoint. Participants were monitored for safety and tolerability for 15 months.
The dose of IL-12 pDNA did not increase pain scores, reactogenicity, or adverse events with the co-administered DNA vaccine, or following the VSV-Gag boost. Injection site pain and reactogenicity were common with intramuscular injections with electroporation, but acceptable to most participants. VSV-Gag vaccine often caused systemic reactogenicity symptoms, including a viral syndrome (in 41%) of fever, chills, malaise/fatigue, myalgia, and headache; and decreased lymphocyte counts 1 day after vaccination.
HIV-MAG DNA vaccine given by intramuscular injection with electroporation was safe at all doses of IL-12 pDNA. The VSV-Gag vaccine at this dose was associated with fever and viral symptoms in some participants, but the vaccine regimens were safe and generally well-tolerated.
Clinical Trials.gov NCT01578889.
•Arsenite (As3+) is positively associated with GDM.•Arsenate (As5+) shows a negative relationship with GDM.•Synergistic effects are found between arsenic and vitamin B12 on GDM.
Growing evidence ...indicates that arsenic (As) exposure can increase the risk of gestational diabetes mellitus (GDM). However, little is known about As species and GDM and the combined effect of As and one-carbon metabolism (OCM) on GDM.
We aimed to examine the associations between As species and GDM and evaluate the potential interactions of folate, vitamin B12, and homocysteine (Hcy) with As species on GDM prevalence.
We measured levels of arsenite (As3+), arsenate (As5+), dimethylarsinic acid (DMA), and arsenobetaine (AsB) species in urine and folate, vitamin B12, and Hcy in serum from 396 pregnant women in Tianjin, China. The diagnosis of GDM was based on an oral glucose tolerance test. Associations of As species in urine with GDM were evaluated using generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR). Additive interactions of As and OCM with GDM were estimated by determining the relative excess risk due to interaction (RERI).
Of the 396 pregnant women, 89 were diagnosed with GDM. Continuous increases in urinary inorganic As were associated with GDM in the GLMs, with adjusted odds ratios of 2.12 (95% CI: 0.96, 4.71) for As3+, and 0.27 (95% CI: 0.07, 0.98) for As5+. The BKMR in estimating the exposure-response functions showed that As3+ and AsB were positively associated with GDM. However, As5+ showed a negative relationship with GDM. Although the additive interactions between As exposure and OCM indicators were not significant, we found that pregnant women with higher urinary As3+ and total As accompanied by lower serum vitamin B12 were more likely to have higher odds of GDM (3.12, 95% CI: 1.32, 7.38 and 3.10, 95% CI: 1.30, 7.38, respectively).
Our data suggest a positive relation between As3+ and GDM but a negative relation between As5+ and GDM. Potential additive interaction of As and OCM with GDM requires further investigation.
A hyperspectral image (HSI) includes a vast quantity of samples, a large number of bands, and randomly occurring redundancy. Classifying such complex data is challenging, and its classification ...performance can be affected significantly by the amount of labeled training samples, as well as the quality, position, and others factors of these samples. Collecting such labeled training samples is labor and time consuming, motivating the idea of taking advantage of labeled samples from other pre-existing related images. Therefore, transfer learning, which can mitigate the semantic gap between existing and new HSIs, has drawn increasing research attention. However, existing transfer learning methods for HSIs (which mainly concentrate on how to overcome the divergence among images) may fail to carefully consider the contents to be transferred and thus limit their performances. In this paper, we present two novel ideas: 1) we, for the first time, introduce an active learning process to initialize the salient samples on the HSI data, which would be transferred later; and 2) we propose constructing and connecting higher level features for the source and target HSI data to further overcome the cross-domain disparity. Different from existing methods, the proposed framework requires no a priori knowledge on the target domain, and it works for both homogeneous and heterogeneous HSI data. Experimental results on three real-world HSIs support the effectiveness of the proposed method for HSI classification.
The WD40-encoding RNA antisense to p53 (WRAP53) is an antisense gene of TP53 with three transcriptional start sites producing three transcript variants involved in the progression of non-small cell ...lung cancer. However, the mechanism by which these different transcript variants regulate non-small cell lung cancer cell behaviors is to be elucidated.
Two non-small cell lung cancer cell lines, A549 cells with wild-type p53 and H1975 with mutated p53, were transfected with WRAP53-1α and WRAP53-1β siRNA. The biological effects were assessed via colony formation, cell viability, apoptosis, cell cycle, wound healing and cell invasion assays, as well as immunoblotting.
Knockdown of WRAP53-1α increased the mRNA and protein levels of p53; suppressed colony formation and proliferation of A549 cells but promoted them in H1975 cells; increased the proportion of cells in the G0/G1 phase in A549 cells but decreased that in H1975 cells; and suppressed migration and invasion in A549 cells but not in H1975 cells. Conversely, knockdown of WRAP53-1β had no effect on p53 expression; promoted the growth of A549 cells but not of H1975 cells; decreased the proportion of cells in the G0/G1 phase in A549 cells but not in H1975 cells; and promoted migration and invasion in A549 cells but not in H1975 cells. Knockdown of both WRAP53-1α and WRAP53-1β promoted apoptosis in A549 cells but not in H1975 cells.
WRAP53 transcript variants exerted different functions in non-small cell lung cancer cells and regulated non-small cell lung cancer cell behaviors depending on the p53 expression.
Change detection approaches based on image segmentation are often used for landslide mapping (LM) from very high-resolution (VHR) remote sensing images. However, these approaches usually have two ...limitations. One is that they are sensitive to thresholds used for image segmentation and require too many parameters. The other one is that the computational complexity of these approaches depends on the image size, and thus they require a long execution time for very high-resolution (VHR) remote sensing images. In this paper, an unsupervised change detection using fast fuzzy c-means clustering (CDFFCM) for LM is proposed. The proposed CDFFCM has two contributions. The first is that we employ a Gaussian pyramid-based fast fuzzy c-means (FCM) clustering algorithm to obtain candidate landslide regions that have a better visual effect due to the utilization of image spatial information. The second is that we use the difference of image structure information instead of grayscale difference to obtain more accurate landslide regions. Three comparative approaches, edge-based level-set (ELSE), region-based level-set (RLSE), and change detection-based Markov random field (CDMRF), and the proposed CDFFCM are evaluated in three true landslide cases in the Lantau area of Hong Kong. The experiments show that the proposed CDFFCM is superior to three comparative approaches in terms of higher accuracy, fewer parameters, and shorter execution time.
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