Learning Diverse Tone Styles for Image Retouching.

Image retouching, aiming to regenerate the visually pleasing renditions of given images, is a subjective task where the users are with different aesthetic sensations. Most existing methods adopt a deterministic model to learn the retouching style from a specific expert, making it less flexible to meet diverse subjective preferences. Besides, the intrinsic diversity of an expert due to the targeted processing of different images is also deficiently described. To circumvent such issues, we propose to learn diverse image retouching with normalizing flow-based architectures. Unlike current flow-based methods which directly generate the output image, we argue that learning in a one-dimensional style space could 1) disentangle the retouching styles from the image content, 2) lead to a stable style presentation form, and 3) avoid the spatial disharmony effects. For obtaining meaningful image tone style representations, a joint-training pipeline is delicately designed, which is composed of a style encoder, a conditional RetouchNet, and the image tone style normalizing flow (TSFlow) module. In particular, the style encoder predicts the target style representation of an input image, which serves as the conditional information in the RetouchNet for retouching, while the TSFlow maps the style representation vector into a Gaussian distribution in the forward pass. After training, the TSFlow can generate diverse image tone style vectors by sampling from the Gaussian distribution. Extensive experiments on MIT-Adobe FiveK and PPR10K datasets show that our proposed method performs favorably against state-of-the-art methods and is effective in generating diverse results to satisfy different human aesthetic preferences. Source codeterministic and pre-trained models are publicly available at https://github.com/SSRHeart/TSFlow.

Nanosized Assemblies from Amphiphilic Solanesol Derivatives for Anticancer Drug Delivery.

Unexpected functionalities of pharmaceutical excipients have been found in some cases. Preplanned introduction of excipients with therapeutic effects might not only reduce the risks of metabolism-related toxicity but also provide synergistic therapeutic effects. Herein, natural original solanesol (SOL), one of the isoprene compounds with some pharmacological activities, was selected to prepare a series of amphiphilic derivatives by chemical modification, and drug delivery systems for oncotherapy were established. Three derivatives, including solanesyl bromide (SOL-Br), monosolanesolsolanesyl succinate (MSS), and solanesylthiosalicylate (STS), were synthesized and formulated into nanosized self-assemblies for doxorubicin (DOX) encapsulation. Meanwhile, polyethylene glycol (PEG) derivatives were synthesized as the stabilizer of solanesol-based self-assemblies, among which hydrazine-poly(ethylene glycol)-hydrazine (PEG6000-DiHZ) was found to be more reliable. The optimized molar ratio between PEG6000-DiHZ and solanesol derivatives was found to be 2:1, considering the drug-loading capacity of self-assemblies. Consistent release profiles were found for the DOX-loaded self-assemblies, in which about 75-80% DOX was cumulatively released within 60 h at pH 5.0. The three DOX-loaded self-assemblies were found to be homogeneous spheres with average particle sizes in the range of 100-200 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Blank self-assemblies were found to have an inhibiting ability toward MCF-7 and HepG-2 cancer cells, which might originate from the inherent nature of solanesol derivatives. In vivo pharmacodynamic experiments demonstrated that blank self-assemblies had certain inhibitory effect on tumor growth compared with the controls. Further enhanced effects were also found for the drug-loaded self-assemblies due to the synergistic anti-tumor effect existing between the drug and the carriers. This work has presented a simple and effective strategy to prepare a therapeutic carrier by direct assembling of the therapeutic compound without PEGylation steps, by which the therapeutic carrier materials could take their effect directly and synergistically along with the loaded drugs.

D-dimer as a predictor of cardiovascular outcomes in patients with diabetes mellitus.

OBJECTIVE: This study aimed to investigate the association between D-dimer and cardiovascular diseases outcomes in patients with type 2 diabetes. METHODS: This is a single-center retrospective cohort study which was performed in a population who had health examinations between 2010 and 2015 in Jiangxi Provincial People's Hospital. All adult patients who were diagnosed with type 2 diabetes were screened. The cardiovascular diseases events were defined as all-cause mortality, new cardiovascular diseases incidence (acute myocardial infarction, unstable angina, stroke), or cardiovascular mortality. RESULTS: The median age was 59.6 years; 50.1% of participants were women; D-dimer was significantly associated with endpoint events. After multivariable adjustment for form of treatments and traditional risk factors, the odds ratio was 3.62 (95% CI 2.07-6.03) for the highest quartile of D-dimer with the lowest quartile as reference. Meanwhile, higher D-dimer levels were associated with a significant and independent higher risk of cause-specific cardiovascular disease events. CONCLUSION: High plasma concentrations of D-dimer were associated with increased risk of cardiovascular diseases events in patients with type 2 diabetes, even after adjusting for cardiovascular risk factors and form of treatments. Measurement of D-dimer may lead to a practical improvement in the current risk stratification criteria for patients with type 2 diabetes.

Effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and its possible mechanisms.

The current study evaluated the effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and investigated its possible mechanisms. 124 patients were randomized to receive 25 mg empagliflozin QD, or placebo double blind for 12 weeks. Patients underwent 24-h ABPM. Endothelial function and arterial stiffness were also measured prior to randomization and at week 12. At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP was - 8.14 mmHg (95% CI - 10.32, - 3.96, P = 0.005). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP was - 5.27 mmHg (95% CI - 8.19, - 1.35, P < 0.001). Changes in office BP were consistent with ABPM. Empagliflozin was well tolerated. Empagliflozin was associated with significant and clinically meaningful reductions in BP versus placebo in Chinese elderly patients with type 2 diabetes and hypertension. The underlying mechanisms possiblely at least in part were the improvements of endothelial function and arterial stiffness associated with empagliflozin.Registration number: ChiCTR2100054678, Registration date: December 23, 2021.

Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome.

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People's Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

Combination of medical and health care based on digital smartphone-powered photochemical dongle for renal function management.

Currently, the global healthcare market is increasing at high speed with the impendent global aging issue. Healthcare Industry 4.0 has emerged as an efficient solution towards the aging issue since it was integrated with ubiquitous medical sensors, big health processing platform, high bandwidth, speed technologies, and medical services, etc. It is believed to fulfil the requirement of the tremendously growing health market. The acquisition of medical data acts as the dominant precondition to implement the Healthcare Industry 4.0. In the same way, the widely available smartphone could serve as the best biomedical information collect station. In this study, a smartphone-powered photochemical dongle is demonstrated to precisely estimate blood creatinine from the fingertip blood, which works as a highly compact reflectance spectral analyzer with an enzymatically dry chemical test strip. Comparing with conventional laboratory facility for the evaluation and treatment of chronic kidney disease (CKD), it implemented the platform of point care with agreed accuracy. In order to estimate the efficiency of treatment and recovery of the CKD, the proposed photochemical dongle would provide a flexible and rapid platform for point of care. Furthermore, the proposed measured technology is very promising method for remote CKD management.

The multi-user evolutionary game simulation in water quality-based water source system.

Water is a crucial factor for human living and maintaining ecological system health. Water resource conflict has become an important factor which restricts regional economic development and affects the harmony and stability of society. This paper, on the one hand, builds a trilateral evolution game model of water intaking in the upper, middle, and lower reaches in terms of water-quality conflict, and makes an analysis of the evolutionary stable strategy of the model on the foundation of a cross-border water resource conflict warning system and based on the view of evolution game. The paper verifies related conclusions by using numerical simulation calculation examples and makes sensitivity analysis of the change of the parameters of the model. The result of the research indicates that (1) there are three groups of system local gradual stable points [Formula: see text] and [Formula: see text] in the trilateral game of water quality-based cross-border conflicts. This means that there are three groups of evolutionary stable strategies: (non-cooperation, non-cooperation, cooperation), (cooperation, non-cooperation, cooperation), and (non-cooperation, cooperation, cooperation). The conclusion obtained via verification by using numerical simulation is that upper and middle reaches are the sections which most likely lead to conflicts, so the strategy selected therefor is (non-cooperation, non-cooperation, cooperation); (2) in water quality-based cross-border conflict, the factor [Formula: see text] of compensation cost increased because excessive transfer of pollutants has a significant effect on water-intaking group strategy evolution path. It is of great theoretical and practical significance to the scientific operation of cross-border water quality and water amount conflicts and the realization of the goal of water resources management.

Comparative effects of 2.5mg levamlodipine and 5mg amlodipine on vascular endothelial function and atherosclerosis.

This study was designed to compare the efficacy of two different racemic antihypertensive drugs on elderly patients with hypertension and their effects on vascular endothelial function and atherosclerosis. A total of 84 elderly hypertensive patients were randomly divided into control and treatment group with 42 patients in each group. The control group was treated with 2.5mg levamlodipine while the treatment group was given 5mg amlodipine. Total effective rate of the treatment group was 90.5%, higher than the control group, that was 71.4% (P<0.05). The time for recovery of related indicators like blood pressure, the total duration of medication were significantly (P<0.05) shorter in the treatment group. Only 1 case of adverse drug reaction was found in the treatment group while 6 cases in control group. Compared to the control group, the treatment group had massive improvement in fingertip pulse volume, flow-mediated dilation of the brachial arteries and endothelin-1 level, carotid intima-media thickness, plaque length & thickness, and blood pressure after the administration. The rate of satisfaction with the in treatment group was 95.3%, higher than that the control group, which was 78.6%. The study concluded that in elderly patients with hypertension, the treatment with 5mg amlodipine enhanced curative effect, fully improved endothelial function & arteriosclerosis and reduced adverse reactions thereby shortening treatment time.

Learning Support Correlation Filters for Visual Tracking.

For visual tracking methods based on kernel support vector machines (SVMs), data sampling is usually adopted to reduce the computational cost in training. In addition, budgeting of support vectors is required for computational efficiency. Instead of sampling and budgeting, recently the circulant matrix formed by dense sampling of translated image patches has been utilized in kernel correlation filters for fast tracking. In this paper, we derive an equivalent formulation of a SVM model with the circulant matrix expression and present an efficient alternating optimization method for visual tracking. We incorporate the discrete Fourier transform with the proposed alternating optimization process, and pose the tracking problem as an iterative learning of support correlation filters (SCFs). In the fully-supervision setting, our SCF can find the globally optimal solution with real-time performance. For a given circulant data matrix with n2 samples of n ×n pixels, the computational complexity of the proposed algorithm is O(n2 logn) whereas that of the standard SVM-based approaches is at least O(n4). In addition, we extend the SCF-based tracking algorithm with multi-channel features, kernel functions, and scale-adaptive approaches to further improve the tracking performance. Experimental results on a large benchmark dataset show that the proposed SCF-based algorithms perform favorably against the state-of-the-art tracking methods in terms of accuracy and speed.

Effectiveness of Coenzyme Q10 Supplementation for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness and safety of coenzyme Q10 for patients with type 2 diabetes mellitus (T2DM). METHODS: Data from randomized controlled trials were obtained to assess the effects of coenzyme Q10 versus placebo or western medicine on patients with T2DM. The study's registration number is CRD42018088474. The primary outcomes included glycosylated hemoglobin, fasting blood glucose, and fasting insulin. RESULT: Thirteen trials involving 765 patients were included. Compared with the control group, coenzyme Q10 may decrease the HbA1c (WMD -0.29; 95% CI -0.54, -0.03; P = 0.03) and the fasting blood glucose (WMD -11.21; 95% CI -18.99, -3.43; P = 0.005). For fasting insulin, there is also not strong evidence that confirms which one is better because there was no statistical difference (WMD -0.48; 95% CI -2.54, 1.57; P = 0.65). CONCLUSION: Based on current evidence, coenzyme Q10 may assist glycemic control, decrease TG, and improve HDL-C in patients with T2DM.

F-SVM: Combination of Feature Transformation and SVM Learning via Convex Relaxation.

The generalization error bound of the support vector machine (SVM) depends on the ratio of the radius and margin. However, conventional SVM only considers the maximization of the margin but ignores the minimization of the radius, which restricts its performance when applied to joint learning of feature transformation and the SVM classifier. Although several approaches have been proposed to integrate the radius and margin information, most of them either require the form of the transformation matrix to be diagonal, or are nonconvex and computationally expensive. In this paper, we suggest a novel approximation for the radius of the minimum enclosing ball in feature space, and then propose a convex radius-margin-based SVM model for joint learning of feature transformation and the SVM classifier, i.e., F-SVM. A generalized block coordinate descent method is adopted to solve the F-SVM model, where the feature transformation is updated via the gradient descent and the classifier is updated by employing the existing SVM solver. By incorporating with kernel principal component analysis, F-SVM is further extended for joint learning of nonlinear transformation and the classifier. F-SVM can also be incorporated with deep convolutional networks to improve image classification performance. Experiments on the UCI, LFW, MNIST, CIFAR-10, CIFAR-100, and Caltech101 data sets demonstrate the effectiveness of F-SVM.

Hydrazone-Containing Triblock Copolymeric Micelles for pH-Controlled Drug Delivery.

In this study, the structure-activity relationship of amphiphilic block copolymer micelles as nanosized drug delivery system was revealed. Firstly, a biodegradable triblock polymers PEG-DiHyd-PLA containing hydrazone bond was synthesized through the ring-opening polymerization. In this method, PEG-DiHyd-Phenol was used as the initiator and L-lactide as the monomer. Then, the polymeric micelles were formed and used as nano-drug carriers with pH sensitivity. The structure and composition of the polymer were characterized by infrared (IR), nuclear magnetic resonance (1H-NMR), and gel permeation chromatography (GPC), we characterized the self-assembling process of the triblock polymers and the pH sensitivity of the micelles by the means of transmission electron microscopy (TEM), dynamic light scattering method (DLS). Doxorubicin (DOX) acts as the model drug, and we researched the capacities of drug loading and release in vitro of the micelles. MTT experiments showed that the blank micelles of PEG-DiHyd-PLA were not cytotoxic to tumor cells (HepG-2, MCF-7) and normal cell (L-02 cells), but the DOX loaded ones displayed more toxicity than the ones without hydrazone, which was consistent to the further confocal laser scanning microscopy and flow cytometry study.

mPEGylated solanesol micelles as redox-responsive nanocarriers with synergistic anticancer effect.

We prepared an amphiphilic redox-responsive conjugate based on mPEGylated solanesol, solanesyl poly(ethylene glycol) dithiodipropionate (SPDP), along with its inert counterpart solanesyl poly(ethylene glycol) succinate (SPGS), which self-assembled in aqueous solution to form redox-responsive micelles. Used as efficient drug carriers for doxorubicin (DOX), the micelles acted as synergistic agents for cancer therapy. Dynamic light scattering (DLS) measurements showed that the SPDP micelles had average diameters of 111nm, which decreased to 88nm after the encapsulation of DOX. The mean diameters and size distribution of the disulfide-containing micelles changed obviously in the presence of the reducing agent glutathione (GSH), whereas no changes occurred in the case of redox-insensitive SPGS micelles. DOX could be loaded into both types of micelles, with drug loading content of about 4.0%. A significantly accelerated release of DOX was triggered by GSH for DOX-loaded SPDP micelles, compared with DOX-loaded SPGS micelles. Blank SPGS and SPDP micelles displayed higher inhibition of HeLa and MCF-7 cell proliferation but less cytotoxicity to normal L-02 cells at similar concentrations. Confocal microscopic observation indicated that a greater amount of DOX was delivered into the nuclei of cells following 9 or 12h incubation with DOX-loaded micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded SPDP micelles over free DOX and DOX-loaded SPGS micelles. All of the data presented here suggested that these SPDP micelles may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs. STATEMENT OF SIGNIFICANCE: Various nanoscale drug carriers were used to enhance therapeutic effect of many drugs. While, the metabolites of high quantities of carriers may cause additional short- or long-term toxicities. In this study, a new systems based on solanesol derivatives was developed for anticancer drug delivery. There are two features for this system. One is solanesol originated bioactivity of the carrier, which will synergistically facilitate therapeutic effect of the encapsulated drug. The other is the redox-responsive drug release behavior adaptable to the glutathione-rich atmosphere of tumor cell. All the hypothesis have been elucidated in this work through in vitro and in vivo studies. It was found that this drug delivery system may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs.

PEGylated Solanesol for Oral Delivery of Coenzyme Q10.

Coenzyme Q10 (CoQ10) is widely used in preventive or curative treatment of cardiovascular diseases. However, CoQ10 exhibits an extremely low solubility in aqueous medium as well as a poor oral bioavailability. Therefore, solanesyl poly(ethylene glycol) succinate (SPGS) and CoQ10 were formulated as CoQ10-SPGS micelles with a high content of CoQ10 to improve the bioavailability of CoQ10 in rat. Findings indicate that, in the CoQ10-SPGS micelles, SPGS is self-assembled into stable nanosized micelles with a CoQ10 loading capacity of more than 39%. The CoQ10-SPGS micelles exhibit an enhanced photostability upon exposure to simulated sunlight. In vivo experiments demonstrate that, as compared to that of the coarse suspensions of CoQ10, there was three-fold enhancement of oral bioavailability for CoQ10-loaded SPGS micelles depending on varying molecular weight of SPGS. In the encapsulation of CoQ10 by SPGS micelles, the self-assembled nanocarriers with strong muco-adhesive properties lead to increases in the solubility and oral absorption of lipophilic CoQ10 nanoparticles.

Hyaluronic-Acid-Based pH-Sensitive Nanogels for Tumor-Targeted Drug Delivery.

A natural polysaccharide-based nanogel has been synthesized and characterized as pH-sensitive drug delivery system for poorly water-soluble anticancer drugs. In this work, methacrylated hyaluronic acid (MAHA) was used to prepared acid degradable nanogels by a surfactant-free polymerization method in water, where 2,2-dimethacroyloxy-1-ethoxypropane (DMAEP) served as a pH labile cross-linker. Nanogels of different cross-linking density were prepared and doxorubicin (DOX) was successfully encapsulated into the nanogels with drug-loading contents (DLC) ranging from 7.67 to 12.15%. An accelerated DOX release was found in acidic conditions. Cytotoxicity study showed that the DOX loaded nanogels have significantly enhanced cytotoxicity in vitro compared with the nonsensitive ones. Confocal microscopy revealed that there was more DOX in the nuclei of tumor cells when incubated with DOX-loaded pH sensitive nanogels for 3 to 12 h. The enhanced anticancer activity of DOX-loaded pH-sensitive nanogels was also verified by in vivo therapeutic study on mice, in which tumor volume evolution was measured and tumor tissues cell apoptosis and proliferation was examined.

Sampling methods for NMR-based metabolomics of Staphylococcus aureus.

To select an appropriate sampling method for comparison of metabolite profiles between planktonic and biofilm Staphylococcus aureus using NMR techniques, we evaluated three methods: quenching-centrifugation (QC), filtration-quenching (FQ) and filtration-quenching-lyophilization (FQL). We found differences in metabolite loss, yield, reproducibility and metabolite profile. QC caused severe metabolite leakage and possible decomposition of nucleotides. FQ achieved high yields and reproducibility, although it had the disadvantages of long filtration and rinse times before quenching. FQL resulted in a loss of a few metabolites and a lower yield due to lyophilization. Although the biomarkers discovered by each method were nearly the same and seemed insensitive to technical variances, we conclude that FQ is the most appropriate sampling method because of its high yield and reproducibility.

Characterization of Chinese liquor starter, "Daqu", by flavor type with 1H NMR-based nontargeted analysis.

"Daqu" is a fermentation starter and substrate complex that is used to initiate fermentations for the production of Chinese liquor (alcoholic spirit). Several different types of Daqu are customary used, having different flavours, i.e. light, strong, or sauce flavor. With the aim to develop objective methods to characterize and distinguish such different types of Daqu, nontargeted analyses of extracts from three typical flavor types of Daqu were carried out using (1)H nuclear magnetic resonance (NMR) spectroscopy. A significant separation of spectra of Daqu of light-flavor, strong-flavor and sauce-flavor types was achieved using principal components analysis. The separation could be attributed to higher levels of glycerol, malate, acetate and N-acetylglutamine in light-flavor Daqu; higher levels of mannitol, betaine, trimethylamine and pyroglutamate in strong-flavor Daqu; and higher levels of lactate, isoleucine, leucine, isovalerate and valine in sauce-flavor Daqu. These metabolites were regarded as the representative metabolites or biomarkers characteristic for each type of Daqu and could be associated with some of the microorganisms that have been reported in Daqu. This study highlights the application of nontargeted analysis techniques based on NMR in process research and quality control in Daqu production and liquor fermentation.