Search

Resveratrol (RES) loaded Zein‐SHA (low‐molecular‐weight sodium hyaluronate) nanoparticles with average diameter of about 152.13 nm and polydispersity index (PDI) of 0.122, which can be used to encapsulate, protect and deliver resveratrol. By measuring ABTS free radical scavenging ability and iron (III) reducing power, it was determined that encapsulated resveratrol has higher in vitro antioxidant activity than free resveratrol. When tested with murine breast cancer cells 4T1, the encapsulated resveratrol also showed higher antiproliferative activity than free resveratrol, with IC50 values of 14.73 and 17.84 μg/ml, respectively. The colloidal form of resveratrol developed in this research may be particularly suitable for functional foods and beverages, as well as dietary supplements and pharmaceutical products., Resveratrol nanoparticles with zein as carrier were successfully prepared. RES nanoparticles have better in vitro antioxidant activity and antitumor effect than free resveratrol. RES could be a natural compound for development of nutraceutical and cosmeceutical products.

As the most common cause of gynecological cancer-related deaths worldwide, ovarian cancer requires novel therapy strategies. Pt(ii)-Based antitumor drugs (e.g. cisplatin) are one of the most successful and frequently used drugs in ovarian cancer chemotherapy at present. However, drug resistance and severe side effects are the major problems in cancer treatment. Herein, the design of a reduction responsive platinum(iv) (Pt(iv))/ursolic acid (UA)/polyethylene glycol (PEG) dual prodrug amphiphile (Pt(iv)-UA-PEG) to treat cisplatin-resistant ovarian cancer is reported for the first time. Pt(iv)-UA-PEG could self-assemble into nanoparticles (Pt(iv)-UA NPs) with a fixed and precise Pt/UA ratio, and a constantly high content of drugs. Pt(iv)-UA NPs could be efficiently taken up by cisplatin-resistant ovarian cancer cells and release the drug in intracellular reductive and acidic environments. In vitro studies show that the released UA and cisplatin have different anticancer mechanisms, and their synergistic effects overcome the detoxification and anti-apoptotic mechanisms of cancer cells. Furthermore, the in vivo results indicate that Pt(iv)-UA NPs have a prolonged blood circulation time, enhanced tumor accumulation, and significantly improved antitumor efficacy in A2780/DDP tumor-bearing mice, without causing any side effects. In summary, our results demonstrate that the development of the stimuli-responsive dual prodrug amphiphile nano-assembly provides a new strategy to overcome drug resistance.

Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG

BACKGROUND: Renal ischemia-reperfusion (I/R) injury often occurs in various clinical events, and its incidence and mortality have been increasing. OBJECTIVE: To investigate the value of contrast enhanced ultrasonography (CEUS) in the monitoring of dexamethasone in the improvement of renal I/R injury in rats. METHODS: Eighteen healthy male Sprague-Dawley rats were randomly divided into sham-operated, I/R, and I/R surgery plus dexamethasone treatment (Dexa) groups. In the I/R group 45-minute renal ischemia with 24 h reperfusion period was monitored. Time-intensity curve (TIC)-derived parameters, which included peak value, time to peak (TP), area under the curve (AUC), and mean transit time (MTT) were compared to the blood creatinine, urea, Caspase-1, and NLRP3 levels. RESULTS: The I/R group showed an increased peak value, prolonged TP and MTT, and greater AUC (P

To investigate the properties of dust in the nuclear region of quasars, we explored the extinction curves of the iron low-ionization broad absorption line (FeLoBAL) quasar SDSS J163004.29+311957.6 and its two analogues. The parameterized extinction curves indicated the Milky Way-like 2175 \AA~ bump features in underlying extinction, which are similar to those seen in the Local Group and a subset of high-redshift star-forming galaxies. Compared to the bump features in the Large Magellanic Clouds (LMC), the detections in this work are much closer to those in the Milky Way (MW). These bump features, as well as those in the high- and low-ionization broad absorption line (BAL) quasars of Zhang et al., are probably the counterpart of the 2175 \AA~ bump features in the quasar environment. This type of dust grain is generally small, easily disrupted by high-energy photons and has difficulty surviving in the radiation field of the active galactic nucleus (AGN). However, due to the presence of absorption-line outflows, the 2175 \AA~ bump feature in quasars, which should be rare, is seen many times in BAL quasars. The shielding effect of outflow clouds allows the MW-like dust grains to be assembled or extends the survival period in the quasar nuclear region. The process, and physical and chemical conditions deserve further observational study and investigation., Comment: 13 pages, 10 figures. Accepted by Astronomy & Astrophysics

Galaxy photometric redshift (photo-$z$) is crucial in cosmological studies, such as weak gravitational lensing and galaxy angular clustering measurements. In this work, we try to extract photo-$z$ information and construct its probability distribution function (PDF) using the Bayesian neural networks (BNN) from both galaxy flux and image data expected to be obtained by the China Space Station Telescope (CSST). The mock galaxy images are generated from the Advanced Camera for Surveys of Hubble Space Telescope ($HST$-ACS) and COSMOS catalog, in which the CSST instrumental effects are carefully considered. And the galaxy flux data are measured from galaxy images using aperture photometry. We construct Bayesian multilayer perceptron (B-MLP) and Bayesian convolutional neural network (B-CNN) to predict photo-$z$ along with the PDFs from fluxes and images, respectively. We combine the B-MLP and B-CNN together, and construct a hybrid network and employ the transfer learning techniques to investigate the improvement of including both flux and image data. For galaxy samples with SNR$>$10 in $g$ or $i$ band, we find the accuracy and outlier fraction of photo-$z$ can achieve $\sigma_{\rm NMAD}=0.022$ and $\eta=2.35\%$ for the B-MLP using flux data only, and $\sigma_{\rm NMAD}=0.022$ and $\eta=1.32\%$ for the B-CNN using image data only. The Bayesian hybrid network can achieve $\sigma_{\rm NMAD}=0.021$ and $\eta=1.23\%$, and utilizing transfer learning technique can improve results to $\sigma_{\rm NMAD}=0.019$ and $\eta=1.17\%$, which can provide the most confident predictions with the lowest average uncertainty., Comment: 22 pages, 12 figures, 3 tables, accepted for publication in RAA

The accuracy of galaxy photometric redshift (photo-$z$) can significantly affect the analysis of weak gravitational lensing measurements, especially for future high-precision surveys. In this work, we try to extract photo-$z$ information from both galaxy flux and image data expected to be obtained by China Space Station Telescope (CSST) using neural networks. We generate mock galaxy images based on the observational images from the Advanced Camera for Surveys of Hubble Space Telescope (HST-ACS) and COSMOS catalogs, considering the CSST instrumental effects. Galaxy flux data are then measured directly from these images by aperture photometry. The Multi-Layer Perceptron (MLP) and Convolutional Neural Network (CNN) are constructed to predict photo-$z$ from fluxes and images, respectively. We also propose to use an efficient hybrid network, which combines MLP and CNN, by employing transfer learning techniques to investigate the improvement of the result with both flux and image data included. We find that the photo-$z$ accuracy and outlier fraction can achieve $\sigma_{\rm NMAD} = 0.023$ and $\eta = 1.43\%$ for the MLP using flux data only, and $\sigma_{\rm NMAD} = 0.025$ and $\eta = 1.21\%$ for the CNN using image data only. The result can be further improved in high efficiency as $\sigma_{\rm NMAD} = 0.020$ and $\eta = 0.90\%$ for the hybrid transfer network. These approaches result in similar galaxy median and mean redshifts ~0.8 and 0.9, respectively, for the redshift range from 0 to 4. This indicates that our networks can effectively and properly extract photo-$z$ information from the CSST galaxy flux and image data., Comment: 11 pages, 8 figures, 2 tables. Accepted for publication in MNRAS

Hyaluronic acid (HA) is a natural polysaccharide that has gained much attention due to its biocompatibility, enzyme degradation capacity and active tumor targeting capacity. Its receptor, CD44, is overexpressed in many kinds of cancers and is associated with tumor progress, infiltration and metastasis. Therefore, many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting. In this review, we systemically overview the basic theory of HA, its receptor and hyaluronidase, then we categorize the studies in HA-based drug delivery systems according to the functions of HA, including tumor-targeting materials, enzyme-sensitive biodegradable modality, pH-sensitive component, reduction-sensitive component, and the gel backbone. Finally, the perspective is discussed., Graphical abstract The review summarizes various applications of hyaluronic acid in tumor targeting drug delivery systems based on the specific CD44-targeting capacity and the hyaluronidase degradation property.Image 1

E. coli thioesterase ‘TesA is an important enzyme in fatty acid production. Medium-chain fatty acids (MCFAs, C6-C10) are of great interest due to their similar physicochemical properties to petroleum-based oleo-chemicals. It has been shown that wild-type ‘TesA had better selectivity for long-chain acyl substrates (≥C16), while the two mutants ‘TesAE142D/Y145G and ‘TesAM141L/E142D/Y145G had better selectivity for medium-chain acyl substrates. However, it is difficult to obtain the selectivity mechanism of substrates for proteins by traditional experimental methods. In this study, in order to obtain more MCFAs, we analyzed the binding mode of proteins (‘TesA, ‘TesAE142D/Y145G and ‘TesAM141L/E142D/Y145G) and substrates (C16/C8-N-acetylcysteamine analogs, C16/C8-SNAC), the key residues and catalytic mechanisms through molecular docking, molecular dynamics simulations and the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA). The results showed that several main residues related to catalysis, including Ser10, Asn73 and His157, had a strong hydrogen bond interaction with the substrates. The mutant region (Met141-Tyr146) and loop107–113 were mainly dominated by Van der Waals contributions to the substrates. For C16-SNAC, except for ‘TesAM141L/E142D/Y145G with large conformational changes, there were strong interactions at both head and tail ends that distorted the substrate into a more favorable high-energy conformation for the catalytic reaction. For C8-SNAC, the head and tail found it difficult to bind to the enzyme at the same time due to insufficient chain length, which made the substrate binding sites more variable, so ‘TesAM141L/E142D/Y145G with better binding sites had the strongest activity, and ‘TesA had the weakest activity, conversely. In short, the matching substrate chain and binding pocket length are the key factors affecting selectivity. This will be helpful for the further improvement of thioesterases.

Immunotherapy has shown encouraging results in various cancers, but the response rates are relatively low due to the complex tumor immunosuppressive microenvironment (TIME). The presence of tumor-associated macrophages (TAMs) and tumor hypoxia correlates significantly with potent immunosuppressive activity. Here, a hemoglobin-poly(e-caprolactone) (Hb-PCL) conjugate self-assembled biomimetic nano red blood cell (nano-RBC) system (V(Hb)) is engineered to deliver chemotherapeutic doxorubicin (DOX) and oxygen for reprogramming TIME. The Hb moiety of V(Hb)@DOX can bind to endogenous plasma haptoglobin (Hp) and specifically target the M2-type TAMs via the CD163 surface receptor, and effectively kill the cells. In addition, the O2 released by the Hb alleviates tumor hypoxia, which further augments the antitumor immune response by recruiting fewer M2-type macrophages. TAM-targeting depletion and hypoxia alleviation synergistically reprogram the TIME, which concurrently downregulate PD-L1 expression of tumor cells, decrease the levels of immunosuppressive cytokines such as IL-10 and TGF-β, elevate the immunostimulatory IFN-γ, enhance cytotoxic T lymphocyte (CTL) response, and boost a strong memory response. The ensuing TAM-targeted chemo-immunotherapeutic effects markedly inhibit tumor metastasis and recurrence. Taken together, the engineered endogenous TAM-targeted biomimetic nano-RBC system is a highly promising tool to reprogram TIME for cancer chemo-immunotherapy.

Introduction COVID-19 is severely affecting countries globally and mortality is high. Xuebijing (XBJ) injection is widely used in the treatment of severe pneumonia and sepsis in China due to its anti-inflammatory effect and immunoregulation. This study investigated whether Xuebijing injection can prevent the cytokine storm and reduce the mortality from severe COVID-19. Methods This was a randomized, double-blinded trial in which 60 eligible patients were recruited from the First people's Hospital of Jingzhou from February 16 to March 25 in 2020. A total of 57 completed the trial, 3 dropped out. The treatment group received routine medication plus Xuebijing injection while the control group received routine medication plus saline. Results The secretion of interleukin-6(IL-6), interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) was suppressed significantly (P

Thrombin is the main target of antithrombotic and anticoagulant therapy. Although recent studies have shown that surface-modified fullerene derivatives can be used as novel nano-anticoagulants to effectively inhibit thrombin, the specific mechanism remains unclear. In this study, we investigated the binding mode and inhibition mechanism of fullerenes with thrombin by using various molecular modelling approaches. The results showed that owing to the hydrophobicity of the fullerene skeleton, the four existing fullerene inhibitors mainly combined with the active site of thrombin through van der Waals interaction and tended to make the surrounding environment hydrophobic. This made the inhibitors with hydrophobic side chains, especially those with large hydrophobic side chains containing benzene rings, have greater binding free energy with protein. However, as more hydrophilic groups can change the surrounding hydrophilic–hydrophobic environment and form more hydrogen bonds, the electrostatic contribution of the polyhydroxy side chain designed in this study was increased further. At the same time, the van der Waals interaction between the fullerene carbon skeleton and protein did not decrease significantly, resulting in a significantly increased total binding free energy and an enhanced inhibition effect. These findings provide a theoretical basis for the improvement of highly effective fullerene anticoagulants.

Background: Contrast-enhanced ultrasound (CEUS) can be used as a noninvasive and quantitative diagnostic method to judge the progression of renal ischemia-reperfusion injury. The aim of this study was to evaluate the blood perfusion of renal cortex during ischemia-reperfusion (I/R) injury by quantitative contrast-enhanced ultrasound (CEUS) parameters.Materials: In this experiment, 24 rabbits were randomly divided into following four groups (N=6): sham-operation group, 24-h post-operation of ischemia-reperfusion injury group (24-h I/R), 3-d post-operation of I/R injury group (3-d I/R) and 5-d post-operation of I/R injury group (5-d I/R). The I/R model was surgically established. CEUS was performed via a GE LOGIQ 9 ultrasound machine, and a time-intensity curve (TIC) in the renal cortex was generated for each group. All quantitative CEUS parameters were derived from TIC and included the following: the curve's peak ascending slope (wash-in slope [WIS]),area under the curve (AUC), time-to-peak (TTP), change in perfusion peak intensity (A), and arrival time (AT), Subsequently, we analyzed the changes in these parameters, as well as the correlation between changes in CEUS parameters and pathological parameters.Results: The values of AT, TTP, and WIS of all I/R groups significantly differed from the sham-operation group (P 0.05). The AT and TTP values peaked at 3 d after I/R surgery, which correlated with the most significant pathological changes at the same time point.Conclusions: Among the quantitative CEUS parameters, AT, TTP, and WIS were found to be sensitive indicators reflecting blood perfusion in renal microcirculation. Hence, these parameters may be useful for dynamically monitoring the severity of tissue damage at the early stage of I/R injury. Collectively, our findings provide compelling evidence for further clinical application of quantitative CEUS analysis.

Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo. Mechanism analysis indicated that miR-4721 directly targetes GSK3β and reduces its expression, which therefore elevates β-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3β are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3β, which thus activates the WNT/β-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future., Graphical Abstract, MicroRNAs play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC), with the regulations between two miRNAs being less reported. Tang and colleagues demonstrated that miR-4721, induced by EBV-miR-BART22, facilitates the progression of NPC. Further experiments both in vitro and in vivo clarified the underlying mechanism.

Introduction Hypertensive intracerebral hemorrhage (HICH) is a severe stroke and treatment using conventional western medicine is far from desirable. It has been suggested that activating blood circulation to remove stasis is safe and effective in the treatment of HICH. This study was to investigate whether Traditional Chinese patent medicine Xuesaitong Injection (XST) combined with conventional western medicine therapy could improve hematoma absorption and enhance neurological recovery of HICH patients. Methods: 224 eligible HICH patients were randomly assigned to either an XST group (XST integrated with western medicine) or a control group (conventional western medicine alone). 206 patients completed the trial. The primary outcome was the rate of functional independent patients with a modified Rankin scale (mRS) score 0–2 at the 90th day follow-up. Secondary outcomes were changes in National Institutes of Health Stroke Scale (NIHSS) scores, activities of daily living (ADL) scores and the hematoma volume after two weeks of intervention. Results: On the 90th day of follow-up, the rate of mRS score 0–2 in the XST group was 49% while 31.7% for control group, with noticeable difference between (P = 0.012). After two weeks of intervention, Hematoma volume (P = 0.006) and Average NIHSS (P = 0.026) scores decreased markedly for XST group than the control one. Average ADL scores in the XST group was 55.2 ± 10.5, and in the control group was 51.8 ± 9.7 (P = 0.018). Conclusion: Combination of XST and conventional western medicine improved intracerebral hematoma absorption remarkably and enhanced neurological recovery. XST could be an effective adjuvant for the treatment of HICH patients.

Multi-stage optimization which invokes a stochastic algorithm restarting with the returned solution of previous stage, has been widely employed in stochastic optimization. Momentum acceleration technique is famously known for building gradient-based algorithms with fast convergence in large-scale optimization. In order to take the advantage of this acceleration in multi-stage stochastic optimization, we develop a multi-stage stochastic gradient descent with momentum acceleration method, named MAGNET, for first-order stochastic convex optimization. The main ingredient is the employment of a negative momentum, which extends the Nesterov’s momentum to the multi-stage optimization. It can be incorporated in a stochastic gradient-based algorithm in multi-stage mechanism and provide acceleration. The proposed algorithm obtains an accelerated rate of convergence, and is adaptive and free from hyper-parameter tuning. The experimental results demonstrate that our algorithm is competitive with some state-of-the-art methods for solving several typical optimization problems in machine learning.