Publications by authors named "Wenbo Guo"

56 Publications

Assessment of Human Exposure to Five Mycotoxins in China by Biomonitoring Approach.

Toxins (Basel) 2021 Oct 28;13(11). Epub 2021 Oct 28.

Key Laboratory of Protected Horticultural Technology, Institute for Agro-Food Standards and Testing Technology, Academy of Agricultural Sciences, Shanghai 201403, China.

This biomonitoring study was conducted to investigate the concentration levels of five mycotoxins in urine samples from 269 healthy volunteers living in the Yangtze River Delta, China. Alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA) and tentoxin (TEN) were detected in 38.3%, 48.7%, 63.9% and 23.4% of urine samples with the concentrations ranging from 0.057 to 45.8 ng/mL, 0.020 to 0.802 ng/mL, 0.050 to 80.6 ng/mL and 0.021 to 0.939 ng/mL, respectively. Altenuene (ALT) was not detected in any urine sample. Based on the urinary concentrations, the probable daily intake (PDI) values of mycotoxins were calculated, and 100%, 99.2-100%, 0.372% and 1.12% of participants exceeded the threshold of toxicological concern (TTC) values for AOH, AME, TeA and TEN, respectively. This study revealed high potential health risks related to the contaminations of major mycotoxins in China and highlighted the necessity for more toxicological studies to provide better basis for further comprehensive risk assessments.
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http://dx.doi.org/10.3390/toxins13110762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625692PMC
October 2021

Estimating tumor mutational burden across multiple cancer types using whole-exome sequencing.

Ann Transl Med 2021 Sep;9(18):1437

Department of Radiation Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Tumor mutational burden (TMB) is emerging as a promising biomarker in immune checkpoint inhibitor (ICI) therapy. Despite whole-exome sequencing (WES) being the gold standard for quantifying TMB, TMB is determined by selected targeted panels in most cases, and WES-derived TMB data are lacking due to the greater cost and complexity. Determining TMB thresholds is another issue that needs attention.

Methods: A total of 309 patients who had received ICI therapy, representing five cancers (listed in "Results"), were recruited. Among them, 269 patients were evaluable for survival analysis. Tumor and matched blood samples from the patients were analyzed using WES and somatic mutations were determined. TMB is defined as the total number of somatic nonsynonymous mutations in the tumor exome in our study. The patients were divided into different TMB subgroups according to a common fixed number (10 mutations/Mb) or the top tertile within each tumor type.

Results: The distribution of WES-derived median TMBs was highly variable across different tumor types, ranging from 2.71 (cholangiocarcinoma) to 2.97 (nervous system tumor), 3.69 (gastric cancer), 4.31 (hepatocellular carcinoma), and 4.64 [colorectal cancer (CRC)] mutations/Mb. In CRC, the survival benefit of TMB-high patients was significant using both the top tertile and the 10 mutations/Mb threshold. In hepatocellular carcinoma, the 10 mutations/Mb threshold showed an advantage over the top tertile threshold. Among patients with nervous system tumors, cholangiocarcinoma, and gastric cancer, no obvious survival differences were observed between the TMB-high and TMB-low groups with either TMB stratification approach.

Conclusions: The TMB threshold criterion may vary for different cancers. Our data suggest that TMB is unable to predict ICI benefit across all cancer types in Chinese patients. However, it may be an effective biomarker for predicting the clinical benefit of ICI therapy for patients with CRC.
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http://dx.doi.org/10.21037/atm-21-4227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506705PMC
September 2021

Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study.

BMC Cancer 2021 Oct 19;21(1):1126. Epub 2021 Oct 19.

Department of Invasive Technology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, China.

Background: Not all patients with unresectable hepatocellular carcinoma (uHCC) benefit from treatment with immune checkpoint inhibitors and molecular-targeted agents. The aim of this retrospective study was to assess the efficacy and safety of pembrolizumab plus lenvatinib plus hepatic arterial infusion chemotherapy (HAIC) versus pembrolizumab plus lenvatinib in selected populations of patients with treatment-naive uHCC exhibiting programmed cell death ligand-1 (PD-L1) staining.

Methods: Consecutive patients with treatment-naive uHCC exhibiting PD-L1 staining who were treated with pembrolizumab plus lenvatinib plus HAIC (PLH) or pembrolizumab plus lenvatinib (PL) were retrospectively identified from our medical centres from 2018 to 2021. HAIC involved oxaliplatin, fluorouracil, and leucovorin (FOLFOX). Follow-up occurred every 3 weeks for 1 year and then every 6 weeks thereafter. The primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the frequency of key adverse events (AEs).

Results: In total, 248 treatment-naive patients were retrospectively reviewed, 78 of whom were ineligible on the basis of the current criteria. Thus, 170 patients (PLH: n = 84, median age 52 years [range, 42-67]; PL: n = 86, 53 years [range, 43-69]) were eligible for the analysis. The median follow-up was 18.6 months (range, 1-26). At the final follow-up, the median OS was 17.7 months (95% confidence interval [CI], 15.2-18.3) in the PLH group versus 12.6 months (95% CI, 11.1-13.7) in the PL group (hazard ratio [HR] 0.52; 95% CI, 0.36-0.75; p = 0.001). A significant difference was also detected in the median PFS (10.9 months [95% CI, 8.7-11.4] for PLH vs. 6.8 months (95% CI, 5.2-7.4) for PL; HR 0.61, 95% CI, 0.43-0.85; p = 0.001). Significant differences in the rate of the key AEs were noted between groups (79.8% for PLH vs. 62.8% for PL, p = 0.015), but these AEs were controllable.

Conclusions: Among selected populations of patients with treatment-naive uHCC exhibiting PD-L1 staining, the PLH regimen may substantially improve the survival benefits compared with the PL regimen with a controllable safety profile.
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http://dx.doi.org/10.1186/s12885-021-08858-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527794PMC
October 2021

Generalized phase unwrapping method that avoids jump errors for fringe projection profilometry.

Opt Express 2021 Aug;29(17):27181-27192

Jump errors easily occur on the discontinuity of the wrapped phase because of the misalignment between wrapped phase and fringe order in fringe projection profilometry (FPP). In this paper, a phase unwrapping method that avoids jump errors is proposed for FPP. By building two other staggered wrapped phases from the original wrapped phase and dividing each period of fringe order into three parts, the proposed generalized tripartite phase unwrapping (Tri-PU) method can be used to avoid rather than compensatorily correct jump errors. It is suitable for the phase unwrapping method assisted by fringe order with a basic wrapped phase and fringe order, no matter which method is used to recover them. The experimental results demonstrate the effectiveness and generality of the proposed method, which is simple to implement and superior to measure complex objects with sharp edges.
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http://dx.doi.org/10.1364/OE.436116DOI Listing
August 2021

Real-time motion-induced error compensation for 4-step phase-shifting profilometry.

Opt Express 2021 Jul;29(15):23822-23834

Phase-shifting profilometry has been widely used in high-accuracy three-dimensional (3D) shape measurement. However, for dynamic scenarios, the object motion will lead to extra phase shift and then motion-induced error. Convenient and efficient motion-induced error compensation is still challenging. Therefore, we proposed a real-time motion-induced error compensation method for 4-step phase-shifting profilometry. The four phase-shifting images are divided into two groups to calculate two corresponding wrapped phases, one from the first three fringes and the other from the last three fringes. As the motion-induced error doubles the frequency of the projected fringes, the average phase can effectively compensate the motion-induced error because there is a π/2 phase shift between the adjacent frames. Furthermore, we designed a time sequence by recycling the projection fringes in a proper order, and the efficiency of 3D reconstruction could be effectively improved. This method performs pixel-wise error compensation, based on which we realized 50 fps real-time 3D measurement by GPU acceleration. Experimental results demonstrate that the proposed method can effectively reduce the motion-induced error.
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http://dx.doi.org/10.1364/OE.433831DOI Listing
July 2021

Production of Toxins in Yellow Peach () upon Artificial Inoculation with .

Toxins (Basel) 2021 09 15;13(9). Epub 2021 Sep 15.

Institute for Agro-Food Standards and Testing Technology, Shanghai Key Laboratory of Protected Horticultural Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China.

The yellow peach (), an important fruit in China, is highly susceptible to infection by sp., leading to potential health risks and economic losses. In the current study, firstly, yellow peaches were artificially inoculated with . Then, the fruits were stored at 4 °C and 28 °C to simulate the current storage conditions that consumers use, and the toxins (ATs) contents from different parts of the fruits were analyzed via ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that the growth of . and the ATs production were dramatically affected by the storage temperature. At 28 °C, the fungi grew rapidly and the lesion diameter reached about 4.0 cm within 15 days of inoculation, while, at 4 °C, the fungal growth was noticeably inhibited, with no significant change in the lesion diameter. To our surprise, high contents of ATs were produced under both storage conditions even though the fungal growth was suppressed. With an increase in the incubation time, the amounts of ATs showed a steady tendency to increase in most cases. Remarkably, alternariol monomethyl ether (AME), alternariol (AOH), and tenuazonic acid (TeA) were detected in the rotten tissue and also in the surrounding tissue, while a large amount of TeA could also be found in the healthy tissue. To the best of our knowledge, this is the first report regarding the production of ATs by the infection of sp. in yellow peach fruits via artificial inoculation under regulated conditions, and, based on the evidence herein, it is recommended that ATs be included in monitoring and control programs of yellow peach management and food safety administration.
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http://dx.doi.org/10.3390/toxins13090656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473313PMC
September 2021

Lenvatinib plus TACE with or without pembrolizumab for the treatment of initially unresectable hepatocellular carcinoma harbouring PD-L1 expression: a retrospective study.

J Cancer Res Clin Oncol 2021 Aug 28. Epub 2021 Aug 28.

Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, China.

Purpose: The aim of this retrospective study was to compare the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatinib-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harbouring programmed cell death ligand-1 (PD-L1) expression.

Methods: Consecutive patients with initial PD-L1-positive uHCC who received pembrolizumab-lenvatinib-TACE or lenvatinib-TACE sequential therapy were retrospectively identified from three medical institutions during 2016-2020. The primary endpoints included the rate of conversion therapy, defined as converting initially uHCC to hepatectomy, overall survival (OS), and progression-free survival (PFS); secondary endpoint was the frequency of key adverse events (AEs).

Results: In total, 220 consecutively recruited patients were retrospectively reviewed, 78 of whom were ineligible according to the current criteria, leaving 142 patients [pembrolizumab-lenvatinib-TACE: n = 70, median age 58 years (range 36-69) and lenvatinib-TACE: n = 72, 57 years (35-68)] who were eligible for the study. The median duration of follow-up was 27 months [95% confidence interval (CI), 26.3-28.7 months]. At the last follow-up, the rate of conversion therapy was 25.7% in the pembrolizumab-lenvatinib-TACE group and 11.1% in the lenvatinib-TACE group (p = 0.025). The median OS was 18.1 months (95% CI 16.5-20.7) in the pembrolizumab-lenvatinib-TACE group versus 14.1 months (95% CI 12.2-16.9) in the lenvatinib-TACE group [hazard ratio (HR) 0.56, 95% CI 0.38-0.83; p = 0.004]. A distinct difference in the median PFS interval between the groups was detected [9.2 months (95% CI 7.1-10.4) in the pembrolizumab-lenvatinib-TACE group vs. 5.5 months (95% CI 3.9-6.6) in the lenvatinib-TACE group (HR 0.60; 95% CI 0.39-0.91; p = 0.006)]. The rates of the key AEs assessed, which were hypertension, nausea, and rash, were higher in the pembrolizumab-lenvatinib-TACE group than in the lenvatinib-TACE group (all p < 0.05).

Conclusion: Among the selected populations of patients with initial PD-L1-positive uHCC, pembrolizumab-lenvatinib-TACE sequential therapy may have promising antitumour activity, with an acceptable conversion rate and a well-characterized safety profile.
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http://dx.doi.org/10.1007/s00432-021-03767-4DOI Listing
August 2021

Berberine-Based Heterogeneous Linear Supramolecules Neutralized the Acute Nephrotoxicity of Aristolochic Acid by the Self-Assembly Strategy.

ACS Appl Mater Interfaces 2021 Jul 11;13(28):32729-32742. Epub 2021 Jul 11.

School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.

Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A-B) via electrostatic attraction and π-π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A-B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A-B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.
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http://dx.doi.org/10.1021/acsami.1c06968DOI Listing
July 2021

scCancer: a package for automated processing of single-cell RNA-seq data in cancer.

Brief Bioinform 2021 05;22(3)

MOE Key Laboratory of Bioinformatics, BNRIST Bioinformatics Division, Department of Automation, Tsinghua University.

Molecular heterogeneities and complex microenvironments bring great challenges for cancer diagnosis and treatment. Recent advances in single-cell RNA-sequencing (scRNA-seq) technology make it possible to study cancer cell heterogeneities and microenvironments at single-cell transcriptomic level. Here, we develop an R package named scCancer, which focuses on processing and analyzing scRNA-seq data for cancer research. Except basic data processing steps, this package takes several special considerations for cancer-specific features. Firstly, the package introduced comprehensive quality control metrics. Secondly, it used a data-driven machine learning algorithm to accurately identify major cancer microenvironment cell populations. Thirdly, it estimated a malignancy score to classify malignant (cancerous) and non-malignant cells. Then, it analyzed intra-tumor heterogeneities by key cellular phenotypes (such as cell cycle and stemness), gene signatures and cell-cell interactions. Besides, it provided multi-sample data integration analysis with different batch-effect correction strategies. Finally, user-friendly graphic reports were generated for all the analyses. By testing on 56 samples with 433 405 cells in total, we demonstrated its good performance. The package is available at: http://lifeome.net/software/sccancer/.
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http://dx.doi.org/10.1093/bib/bbaa127DOI Listing
May 2021

Data-driven analysis of the electronic-structure factors controlling the work functions of perovskite oxides.

Phys Chem Chem Phys 2021 Mar 16;23(11):6880-6887. Epub 2021 Mar 16.

Department of Materials Science and Engineering, and Materials Research Institute, The Pennsylvania State University, University Park, PA, USA.

Tuning the work functions of materials is of practical interest for maximizing the performance of microelectronic and (photo)electrochemical devices, as the efficiency of these systems depends on the ability to control electronic levels at surfaces and across interfaces. Perovskites are promising compounds to achieve such control. In this work, we examine the work functions of more than 1000 perovskite oxide surfaces (ABO) using data-driven (machine-learning) analysis and identify the factors that determine their magnitude. While the work functions of the BO-terminated surfaces are sensitive to the energy of the hybridized oxygen p bands, the work functions of the AO-terminated surfaces exhibit a much less trivial dependence with respect to the filling of the d bands of the B-site atom and of its electronic affinity. This study shows the utility of interpretable data-driven models in analyzing the work functions of cubic perovskites from a limited number of electronic-structure descriptors.
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http://dx.doi.org/10.1039/d0cp05595fDOI Listing
March 2021

Integrative Genomic Analysis of Gemcitabine Resistance in Pancreatic Cancer by Patient-derived Xenograft Models.

Clin Cancer Res 2021 Jun 5;27(12):3383-3396. Epub 2021 Mar 5.

MOE Key Laboratory of Bioinformatics, Division of BNRist Bioinformatics, Department of Automation, Tsinghua University, Beijing, P.R. China.

Purpose: Gemcitabine is most commonly used for pancreatic cancer. However, the molecular features and mechanisms of the frequently occurring resistance remain unclear. This work aims at exploring the molecular features of gemcitabine resistance and identifying candidate biomarkers and combinatorial targets for the treatment.

Experimental Design: In this study, we established 66 patient-derived xenografts (PDXs) on the basis of clinical pancreatic cancer specimens and treated them with gemcitabine. We generated multiomics data (including whole-exome sequencing, RNA sequencing, miRNA sequencing, and DNA methylation array) of 15 drug-sensitive and 13 -resistant PDXs before and after the gemcitabine treatment. We performed integrative computational analysis to identify the molecular networks related to gemcitabine intrinsic and acquired resistance. Then, short hairpin RNA-based high-content screening was implemented to validate the function of the deregulated genes.

Results: The comprehensive multiomics analysis and functional experiment revealed that and had strong effects on cell proliferation, and and contributed to gemcitabine resistance in pancreatic cancer cells. Moreover, we found miR-135a-5p was significantly associated with the prognosis of patients with pancreatic cancer and could be a candidate biomarker to predict gemcitabine response. Comparing the molecular features before and after the treatment, we found that PI3K-Akt, p53, and hypoxia-inducible factor-1 pathways were significantly altered in multiple patients, providing candidate target pathways for reducing the acquired resistance.

Conclusions: This integrative genomic study systematically investigated the predictive markers and molecular mechanisms of chemoresistance in pancreatic cancer and provides potential therapy targets for overcoming gemcitabine resistance.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3975DOI Listing
June 2021

The prognostic role of ovarian endometriosis in symptomatic adenomyosis patients underwent uterine artery embolization.

Ann Palliat Med 2021 Mar 7;10(3):2577-2583. Epub 2021 Feb 7.

Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: To explore the prognostic role of ovarian endometriosis in symptomatic adenomyosis patients underwent uterine artery embolization (UAE).

Methods: This was a retrospective, single-center study. A total of 76 patients with adenomyosis who underwent UAE in The First Affiliated Hospital of Sun Yat-sen University between May 2009 and July 2016 were enrolled in this study. These patients were divided into two groups based on whether complicated with ovarian endometriosis. After UAE, the patients were followed up for 12 months. The improvements of dysmenorrhea and menorrhagia were evaluated according to the symptom relief criteria. The improvement rates in both groups were analyzed and compared.

Results: Among the 76 patients with adenomyosis, 17 (22.3%) were diagnosed with OE and 59 (77.6%) were non-OE. In the OE group, all patients (17/17, 100%) had dysmenorrhea and 11 (11/17, 64.7%) had menorrhagia. In non-OE group, 57 patients (57/59, 96.6%) had dysmenorrhea and 50 (50/59, 84.7%) had menorrhagia. The improvement rates of dysmenorrhea in the two groups were 47.1% (OE group) and 86.0% (non-OE group), respectively (P<0.05). The improvement rates of menorrhagia in the two groups were 63.6% (OE group) and 84.0% (non-OE group), respectively (P=0.263).

Conclusions: Patients without OE showed a lower incidence of dysmenorrhea and may have an advantage in the improvement of dysmenorrhea compared with those with OE when they underwent UAE. However, no significant difference was observed in the improvement of menorrhagia.
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http://dx.doi.org/10.21037/apm-20-1381DOI Listing
March 2021

Examining geographical disparities in the incubation period of the COVID-19 infected cases in Shenzhen and Hefei, China.

Environ Health Prev Med 2021 Jan 18;26(1):10. Epub 2021 Jan 18.

Harbin Institute of Technology, Shenzhen, Guangdong, China.

Background: Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions.

Methods: This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei.

Results: The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods.

Conclusion: Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.
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http://dx.doi.org/10.1186/s12199-021-00935-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812984PMC
January 2021

Comparison of Nanomaterials with Other Unconventional Materials Used as Additives for Soil Improvement in the Context of Sustainable Development: A Review.

Nanomaterials (Basel) 2020 Dec 23;11(1). Epub 2020 Dec 23.

MOE Key Laboratory of High-speed Railway Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.

Since the concept of sustainable development enjoys popular support in the 21st century, various kinds of unconventional materials were introduced for soil improvement in the past few decades to replace the traditional materials like concrete and lime. This paper compared nanomaterials with other three kinds of representative unconventional materials to demonstrate its superiority in soil treatment. The other three kinds of unconventional materials include microbially induced calcite precipitation (MICP), recycled tire and environmental fiber. Nanomaterial and MICP have a comprehensive effect on soil reinforcement, since they can improve shear strength, adjust permeability, resist liquefaction and purify the environment. Recycled tire and environmental fibers are granular materials that are mostly adopted to reinforce reconstituted soil. The reinforcement mechanisms and effects of these four kinds of unconventional materials are discussed in detail, and their price/performance ratios are calculated to make an evaluation about their market application prospects. It can be seen that nanomaterials have promising prospects. Colloidal silica, bentonite and laponite present a satisfactory effect on liquefaction mitigation for sandy foundation, and carbon nanotube has an aptitude for unconfined compressive strength improvement. Among the investigated nanomaterials, colloidal silica is the closest to scale market application. Despite the advantages of nanomaterials adopted as additives for soil improvement, they are known for unwanted interactions with different biological objects at the cell level. Nevertheless, research on nanomaterials that are adopted for soil improvement are very promising and can intensify the relationship between sustainable development and geotechnical engineering through innovative techniques.
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http://dx.doi.org/10.3390/nano11010015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823269PMC
December 2020

A reliable and accurate UHPLC-MS/MS method for screening of , and mycotoxins in orange, grape and apple juices.

Anal Methods 2021 01;13(2):192-201

Institute for Agro-food Standards and Testing Technology, Shanghai Key Laboratory of Protected Horticultural Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China.

An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for simultaneous determination of 15 mycotoxins, including aflatoxins (B1, B2, G1, and G2), ochratoxins (A, B, and C), citrinin, patulin, and emerging Alternaria toxins (alternariol, alternariol monomethyl ether, altenuene, tentoxin, tenuazonic acid, and altenusin) in orange, grape and apple juices. Different extraction approaches, sorbents, chromatographic columns and mobile phases were investigated for establishment of an optimal QuEChERS procedure and UHPLC-MS/MS conditions. Recoveries were in the range of 74-110%, and the limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.05 to 0.1 ng mL-1 and from 0.1 to 5.0 ng mL-1, respectively. Matrix effects were evaluated and matrix-matched calibration curves were used to compensate for matrix effects and achieve accurate quantification. The correlation coefficients (R2) of linearity were higher than 0.99 and the relative standard deviations (RSDs) of intra- and inter-day precision were under 13%. The method was subsequently applied to 22 fruit juice samples. The high frequencies (90.9%) of mycotoxins not only proved the reliability and sensitivity of the currently established method, but also demonstrated that fruit juices are susceptible to different mycotoxins, which need to be continuously monitored in the future.
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http://dx.doi.org/10.1039/d0ay01787fDOI Listing
January 2021

Efficacy and Safety of Transarterial Chemoembolization Combined With Anlotinib for Unresectable Hepatocellular Carcinoma: A Retrospective Study.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820965587

The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.

Objective: This study aimed to explore the efficacy and safety of using transarterial chemoembolization (TACE) combined with anlotinib in patients with unresectable hepatocellular carcinoma, compared with TACE alone.

Methods: This was a single-center study, retrospectively recruited 82 unresectable HCC patients who received either TACE alone (TA group; n = 46) or TACE combined with anlotinib (TC group; n = 36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS). While the secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and main complications. Log-rank test and Kaplan-Meier method was used to calculate the survival difference. All statistical tests were 2-sided and P value <0.05 were taken as statistically significant.

Results: Patients in TC group had a significant higher PFS than those in TA group (7.35 months vs. 5.54 months, p = 0.035). Although 3-month survival rate in the 2 groups was not statistically different (97.2% vs. 93.5%, p = 0.627), the survival rate at 6 months and 1 year were strongly higher in TC group (83.3% vs. 56.5%, p = 0.016; 66.7% vs. 19.6%, respectively, p < 0.05). Furthermore, there was a significantly higher ORR in TC group, while no statistical difference existed in DCR. Neither treatment-related mortality nor grade 4 adverse events (AEs) occurred. However, 2 patients in TC group had grade 3 AEs (one suffered with erythra, and the other with hand-foot-skin reaction), which disappeared after prompt treatment.

Conclusion: TACE combined with anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. Randomized controlled trials are warranted to further evaluate treatment effects of anlotinib in HCC.
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http://dx.doi.org/10.1177/1533033820965587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586029PMC
November 2021

Self-assembled natural phytochemicals for synergistically antibacterial application from the enlightenment of traditional Chinese medicine combination.

Acta Pharm Sin B 2020 Sep 30;10(9):1784-1795. Epub 2019 Dec 30.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.

The application of nanotechnology for antimicrobial delivery has capacity to improve antibacterial efficacy. Currently, the usage of various inorganic and organic carriers, such as metal ions, nano-silicon and surfactants, might increase the potential toxicity of nanoparticles and make their clinical transformation more difficult. Herein, a nano-delivery system was constructed by direct self-assembly of antibacterial phytochemicals (berberine and rhein) originated from traditional Chinese medicine Franch. and L., respectively. Combining X-ray single crystal diffraction, nuclear magnetic resonance and other spectra characterizations, the stacked structure of nanoparticles was profoundly demonstrated. Briefly, rhein acted as the layered backbone and berberine embedded in it. bacteriostasis experiment showed the minimum bactericidal concentration of nanoparticles was 0.1 μmol/mL, which was lower than that of berberine and rhein. The results of confocal laser scanning microscope, biofilm quantitive assay and scanning electron microscopy indicated that nanoparticles had strong inhibitory effects on biofilm. More importantly, transmission electron microscopy and mass spectra indicated the further bacteriostatic mechanism of nanoparticles. Meanwhile, the nanoparticles had well biocompatibility and safety. Current study will open up new prospect that the design of self-assemblies between active phytochemicals can be originated from traditional Chinese medicine combination.
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http://dx.doi.org/10.1016/j.apsb.2019.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564035PMC
September 2020

Determinants of pain in advanced HCC patients recieving hepatic artery infusion chemotherapy.

Invest New Drugs 2021 04 1;39(2):394-399. Epub 2020 Oct 1.

Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, China.

Purpose Hepatic arterial infusion chemotherapy (HAIC) is one of the options to treat unresectable hepatocellular carcinoma (HCC). The majority of HCC patients suffer great pain in the course of HAIC treatment. To improve the quality of life and the efficacy of HAIC treatment, the causes of pain, the choice of an analgesic regimen, and the relationship between pain and prognosis of HCC were analyzed. Methods A total of 376 HCC patients under HAIC in our hospital were recriuted between March 2017 and September 2019. Multivariate linear regression analysis (stepwise) was used to calculate the potential factors related to the severe pain in HCC patients under HAIC. Analgesics treatments were carried out based on the results of the visual analogue scale (VAS) score which was used to evaluate the pain. Results The mean value of the VAS score is 3.604, which indicates that the pain in most patients is mild and endurable. Intra-arterial lidocaine injection is an effective method in most patients (96%, 361 of 376), and the total score of VAS is reduced from 1355 to 195 following lidocaine injection. Multivariate analysis suggestes that oxaliplatin (OXA) preparation time, hepatic artery diameter and OXA manufacturers (R = 0.859) are influential factors for pain scores. Conclusion This study demonstrates an effective way to systematically assess and ease pain in HCC patients with HAIC treatment. OXA preparation time, hepatic artery diameter, and OXA manufacturers are the potential influencing factors for pain. This work presented here will provide a detailed understanding of the clinical application of HAIC in advanced HCC patients.
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http://dx.doi.org/10.1007/s10637-020-01009-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960585PMC
April 2021

Correction: Cui, H., et al. BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation. 2019, , 4062.

Int J Mol Sci 2020 Sep 17;21(18). Epub 2020 Sep 17.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.

The authors wish to make the following corrections to this paper [...].
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http://dx.doi.org/10.3390/ijms21186814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555197PMC
September 2020

Real-time 3D shape measurement with dual-frequency composite grating and motion-induced error reduction.

Opt Express 2020 Aug;28(18):26882-26897

Phase-shifting profilometry has been increasingly sought and applied in dynamic three-dimensional (3D) shape measurement. However, the object motion will lead to extra phase shift error and thus measurement error. In this paper, a real-time 3D shape measurement method based on dual-frequency composite phase-shifting grating and motion-induced error reduction is proposed for a complex scene containing dynamic and static objects. The proposed method detects the motion region of a complex scene through the phase relations of the dual-frequency composite grating and reduces the motion-induced error with the combination of the phase calculated by a phase-shifting algorithm and the phase extracted by Fourier fringe analysis. It can correctly reconstruct the 3D shape of a complex dynamic scene and ensure high measurement accuracy of its static object as well. With the aid of the phase-shifting image ordering approach, the dynamic 3D shape of complex scenes can be reconstructed and the motion-induced error can also be suppressed in real time. Experimental results well proved that the proposed method is effective and practical.
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http://dx.doi.org/10.1364/OE.403474DOI Listing
August 2020

Efficacy and safety of hepatic arterial infusion chemotherapy combined with transarterial embolization for unresectable hepatocellular carcinoma: A propensity score-matching cohort study.

JGH Open 2020 Jun 13;4(3):477-483. Epub 2019 Dec 13.

Department of Interventional Radiology The First Affiliated Hospital of Sun Yat-Sen University Guangzhou Guangdong Province China.

Purpose: The aim of this study was to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen combined with transarterial embolization (TAE + HAIC) in patients with unresectable hepatocellular carcinoma (HCC).

Methods: Unresectable HCC patients treated with TAE + HAIC and conventional transcatheter arterial chemoembolization (TACE), respectively, between January 2015 and October 2016 in China were retrospectively assessed. The primary outcome was progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), the disease control rate (DCR), and main complications. Propensity score matching (PSM) was estimated by multiple logistic regression using caliper matching (caliper 0.2). A Cox proportional hazards model was used to identify those factors shown to be associated with PFS.

Results: A total of 113 patients were analyzed, with 41 and 72 receiving TAE + HAIC and TACE, respectively. After PSM, 35 pairs of patients were assessed. The median PFS was 7.93 months (95% confidence interval [CI], 4.44-11.42) for the TAE + HAIC group, which was higher compared with 2.60 months (95% CI, 0.93-4.27, = 0.003) for TACE. The subgroup with Barcelona clinic liver cancer (BCLC) stage C obtained more PFS benefit from TAE + HAIC ( = 0.002). ORRs in the TAE + HAIC and TACE groups were 37.14% (13/35) and 20.00% (7/35, = 0.112), respectively; DCRs were 88.57% (31/35) and 60.00% (21/35, = 0.006), respectively. Abundant blood supply (hazard ratio [HR] =0.327, 95% CI 0.173-0.615,  < 0.001) and TAE + HAIC (HR = 0.332, 95% CI 0.177-0.621,  < 0.001) were associated with longer PFS in multivariate analysis.

Conclusions: Compared with conventional TACE, TAE + HAIC provides more PFS benefits to patients with unresectable HCC, especially in those with BCLC stage C.
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http://dx.doi.org/10.1002/jgh3.12285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273730PMC
June 2020

Examining the incubation period distributions of COVID-19 on Chinese patients with different travel histories.

J Infect Dev Ctries 2020 04 30;14(4):323-327. Epub 2020 Apr 30.

Harbin Institute of Technology, Shenzhen, Guangdong, China.

Introduction: Current studies estimated a general incubation period distribution of COVID-19 based on early-confirmed cases in Wuhan, and have not examined whether the incubation period distribution varies across population segments with different travel histories. We aimed to examine whether patients infected by community transmission had extended incubation periods than the early generation patients who had direct exposures to Wuhan.

Methodology: Based on 4741 patient case reports from municipal centers of disease control by February 21, 2020, we calculated the incubation periods of 2555 patients with clear epidemiological survey information and illness development timeline. All patients were categorized into five groups by their travel histories. Incubation period distributions were modeled for each group by the method of the posterior Weibull distribution estimation.

Results: Adults aged 30 to 59 years had the most substantial proportion of confirmed cases in China. The incubation period distribution varied slightly across patient groups with different travel histories. Patients who regularly lived in Wuhan and left to other locations before January 23, 2020 had the shortest posterior median value of 7.57 days for the incubation period, while the incubation periods for persons affected by local community transmission had the largest posterior median of incubation periods, 9.31 days.

Conclusions: The median incubation period for all patients infected outside Wuhan was 9 days, a bit of more extended than the early estimated 5-day incubation period that was based on patients in Wuhan. Our findings may imply the decreases of virulence of the COVID-19 virus along with intergenerational transmission.
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http://dx.doi.org/10.3855/jidc.12718DOI Listing
April 2020

Individual and combined cytotoxic effects of T-2 toxin and its four metabolites on porcine Leydig cells.

Food Chem Toxicol 2020 May 23;139:111277. Epub 2020 Mar 23.

Institute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai, 201403, China. Electronic address:

T-2 toxin, one of the most toxic mycotoxins, is commonly presented along with its metabolites, HT-2 toxin, neosolaniol (NEO), T-2 triol, and T-2 tetraol in foodstuff and feed. The aim of this study was to evaluate the cytotoxic effects of T-2 toxin alone and in combination with its metabolites on porcine Leydig cells. Based on the determination of cell viability with CCK-8, toxicological interactions were investigated using Combination Index method. The cytotoxic potency of five tested mycotoxins individual and their mixtures all showed with a dose-dependent manner. In view of IC values, the decreasing cytotoxicity of mycotoxins was ranking: T-2 toxin > HT-2 toxin > T-2 triol > NEO > T-2 tetraol. Combinations of T-2+HT-2, T-2+NEO, and HT-2+NEO displayed synergism at low doses but antagonism at high doses, while the ternary combination of T-2+HT-2+NEO revealed adverse situation from antagonism to synergism. All binary and ternary combinations of T-2 toxin, T-2 triol, and T-2 tetraol exhibited antagonistic interactions. Our results suggest that the co-occurrence of T-2 toxin and its metabolites might pose a slight threat to reproductive health due to antagonistic interactions. However, the synergy observed should be not ignored especially at low doses of mycotoxins co-occurrence in the diet.
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http://dx.doi.org/10.1016/j.fct.2020.111277DOI Listing
May 2020

Ochratoxin A in human blood plasma samples from apparently healthy volunteers in Nanjing, China.

Mycotoxin Res 2020 Aug 3;36(3):269-276. Epub 2020 Feb 3.

Institute for Agro-food Standards and Testing Technology, Shanghai Key Laboratory of Protected Horticultural Technology, Shanghai Academy of Agricultural Sciences, Shanghai, 201403, China.

This study was conducted to investigate the exposure to ochratoxin A (OTA) of populations living in Nanjing, China. Plasma samples were collected from 147 healthy adults (age 18-63 years) and analyzed for OTA by a reliable and sensitive ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method (limit of detection 0.04 ng/mL). After enzymatic hydrolysis by β-glucuronidase/arylsulfatase, OTA was detected in 80.9% plasma samples with mean concentration of 0.26 ± 0.59 ng/mL (range 0.04-6.59 ng/mL). The estimated daily intakes of OTA based on plasma concentrations (mean 0.51 ng/kg bw/day, max 12.99 ng/kg bw/day) were lower than the tolerable daily intake published by European Food Safety Authority (EFSA) or Joint FAO/WHO Expert Committee on Food Additives (JFECFA) indicative of rare risks related to the OTA exposure in the investigated area. This study provides a valuable insight on human exposure to OTA in China. Further studies in children and elder people and in adult cohorts from other regions are recommended.
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http://dx.doi.org/10.1007/s12550-020-00387-8DOI Listing
August 2020

T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line.

Toxins (Basel) 2020 01 10;12(1). Epub 2020 Jan 10.

Institute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai, 201403, China.

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis.
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http://dx.doi.org/10.3390/toxins12010043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020450PMC
January 2020

Self-Assemblies Based on Traditional Medicine Berberine and Cinnamic Acid for Adhesion-Induced Inhibition Multidrug-Resistant .

ACS Appl Mater Interfaces 2020 Jan 20;12(1):227-237. Epub 2019 Dec 20.

School of Chinese Pharmacy , Beijing University of Chinese Medicine , Beijing 102488 , P. R. China.

is resistant to various first-line antibiotics, and seeking multifarious strategies aimed at effective control of antibiotic-resistant behavior is urgently needed. Here, we report a two-component directed self-assembly mode: the phytochemicals berberine and cinnamic acid can directly self-assemble into nanoparticles (NPs) displaying good bacteriostastic activity. Compared with several first-line antibiotics, the obtained nanostructures have a better inhibitory effect on multidrug-resistant (MRSA) and stronger ability for biofilm removal. These qualities are attributed to the fact that organic assemblies can first spontaneously adhere to the surface of the bacteria, infiltrate into the cell, and then lead to converging attack against MRSA; thereafter, multipath bactericidal mechanisms of NPs on MRSA are found by both transcriptomic analysis and quantitative Polymerase Chain Reaction analysis. Moreover, when combined with spectral data and single crystal X-ray diffraction, the NPs' self-assembly mechanism governed by hydrogen bonds and π-π stacking interactions is clearly elucidated. These non-covalent interactions induce the NPs' formation of butterfly-like one-dimensional self-assembled units and finally layered three-dimensional spatial configuration. In addition, biocompatibility tests show that the NPs are nonhemolytic with little toxicity in vitro and in vivo. This directed self-assembly mode can offer a new perspective toward the design of biocompatible antimicrobial nanomedicines for clinical translation.
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http://dx.doi.org/10.1021/acsami.9b17722DOI Listing
January 2020

Design, Synthesis and Biological Evaluation of Diosgenin-Amino Acid Derivatives with Dual Functions of Neuroprotection and Angiogenesis.

Molecules 2019 Nov 7;24(22). Epub 2019 Nov 7.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.

Diosgenin, a natural product with steroidal structure, has a wide range of clinical applications in China. It also shows great potential in the treatment of blood clots and nerve damage. To enhance the bioavailability as well as efficacy of diosgenin, eighteen diosgenin-amino acid derivatives were designed and synthesized. The neuroprotective effects of these compounds were evaluated by SH-SY5Y cell line and the biosafety was evaluated by H9c2 cell line. The results displayed that part of the derivatives' activities (EC < 20 μM) were higher than positive control edaravone (EC = 21.60 ± 3.04 μM), among which, DG-15 (EC = 6.86 ± 0.69 μM) exhibited the best neuroprotection. Meanwhile, biosafety evaluation showed that DG-15 had no cytotoxicity on H9c2 cell lines. Interestingly, combined neuroprotective and cytotoxic results, part of the derivatives without their protecting group were superior to compounds with protecting group. Subsequently, Giemsa staining and DAPI (4',6-diamidino-2-phenylindole) staining indicated that DG-15 had a protective effect on damaged SH-SY5Y cells by reducing apoptosis. Moreover, DG-15 showed a higher role in promoting angiogenesis at high concentrations (4 mg/mL) on the chorioallantoic membrane model. This finding displayed that DG-15 had dual functions of neuroprotection and angiogenesis, which provided further insight into designing agent for the application in treatment of ischemic stroke.
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http://dx.doi.org/10.3390/molecules24224025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891328PMC
November 2019

Synthesis of Novel Baicalein Amino Acid Derivatives and Biological Evaluation as Neuroprotective Agents.

Molecules 2019 Oct 9;24(20). Epub 2019 Oct 9.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China.

Baicalein, a famously effective component of the traditional Chinese medicine Rhizoma Huang Qin ( L.), has been proved to have potent neuroprotection and anti-platelet aggregation effects with few side effects. Meanwhile, recent studies have revealed that the introduction of amino acid to baicalein could improve its neuroprotective activity. In the present study, a series of novel baicalein amino acid derivatives were designed, synthesized, and screened for their neuroprotective effect against -butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells and toxicity on the normal H9C2 cell line by standard methylthiazol tetrazolium (MTT) assay. In addition, all of the newly synthesized compounds were characterized by H-NMR, C-NMR, and high resolution mass spectrometry (HR-MS). The results showed that most of the compounds provided more potent neuroprotection than baicalein, and were equivalent to the positive drug edaravin. They showed no obvious cytotoxicity on normal H9C2 cells. Notably, the most active compound displayed the highest protective effect (50% effective concentration (EC) = 4.31 μM) against -butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells, which was much better than the baicalein (EC = 24.77 μM) and edaravin (EC = 5.62 μM). Further research on the chick chorioallantoic membrane (CAM) model indicated that compound could significantly increase angiogenesis, which might promote neurovascular proliferation. The detection of apoptosis analysis showed that compound could dramatically alleviate morphological manifestations of cell damage. Moreover, the benzyloxycarbonyl (cbz)-protected baicalein amino acid derivatives showed better neuroprotective activity than the -Butyloxy carbonyl (boc)-protected derivatives.
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http://dx.doi.org/10.3390/molecules24203647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832219PMC
October 2019

High-speed three-dimensional shape measurement based on shifting Gray-code light.

Opt Express 2019 Aug;27(16):22631-22644

The measuring technique combining a phase-shifting algorithm and Gray-code light has been widely used in three-dimensional (3D) shape measurement for static scenes because of its high robustness and anti-noise ability. However, in the high-speed measurement, phase unwrapping errors occur easily on the boundaries of adjacent Gray-code words because of the defocus of the projector, the motion of the objects and the non-uniform reflectivity of the surface. To overcome this challenge, a high-speed 3D shape measurement method based on shifting Gray-code light has been proposed in this paper. Firstly, the average intensity of three captured phase-shifting fringe images are used as a pixel-wise threshold to binarize the Gray codes and to eliminate most phase unwrapping errors caused by the non-uniform reflectivity, ambient light variations, and the defocus of projector. Then, the shifting Gray-code (SGC) coding strategy is proposed to avoid the remaining errors of phase unwrapping on the edge of the code words. In this strategy, no additional patterns are projected, and two sets of decoding words with staggered boundaries are built in the temporal sequences for one wrapped phase. Finally, the simple, efficient, and robust phase unwrapping can be achieved in the high-speed dynamic measurement. This proposed method has been applied to reconstruct 3D shape of randomly collapsing objects in a large depth range, and the experimental results demonstrate that it can reliably obtain high-quality shape and texture information at 310 frames per second.
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http://dx.doi.org/10.1364/OE.27.022631DOI Listing
August 2019

BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation.

Int J Mol Sci 2019 Aug 20;20(16). Epub 2019 Aug 20.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.

There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine-betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and . According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs.
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http://dx.doi.org/10.3390/ijms20164062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720627PMC
August 2019
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