Publications by authors named "Chen Cheng"

1,826 Publications

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Design, synthesis, and anticancer evaluation of novel andrographolide derivatives bearing an α,β-unsaturated ketone moiety.

Bioorg Chem 2021 Apr 24;112:104941. Epub 2021 Apr 24.

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

A series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory activities against both HCT116 and MCF-7 cell lines, with IC values of 2.49 and 7.80 μM respectively. Preliminary anticancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 10b against HCT116 using flow cytometry, and the results indicated that 10b blocked the proliferation of HCT116 cells by inducing cell apoptosis in a concentration-dependent manner and arresting cell cycle in G/M phase.
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http://dx.doi.org/10.1016/j.bioorg.2021.104941DOI Listing
April 2021

Developing Bright GFP-Like Fluorogens for Live-Cell Imaging with Nonpolar Protein-Chromophore Interactions.

Chemistry 2021 May 2. Epub 2021 May 2.

Oregon State University, Department of Chemistry, 153 Gilbert Hall, 97331, Corvallis, UNITED STATES.

Fluorescence-activating proteins (FAPs) that bind a chromophore and activate its fluorescence have gained popularity in bioimaging. The fluorescence-activating and absorption-shifting tag (FAST) is a light-weight FAP that enables fast reversible fluorogen binding, thus advancing multiplex and super-resolution imaging. However, the rational design of FAST-specific fluorogens with large fluorescence enhancement (FE) remains challenging. Here, we report a novel fluorogen directly engineered from green fluorescent protein (GFP) chromophore by a unique double-donor-one-acceptor strategy, which exhibits an over 550-fold FE upon FAST binding and a high extinction coefficient of ~100,000 M -1 ·cm -1 . Correlation analysis of the excited state nonradiative decay rates and environmental factors reveal that the large FE is caused by nonpolar protein-fluorogen interactions. Our deep insights into structure-function relationships could guide the rational design of bright fluorogens for live-cell imaging with extended spectral properties such as redder emissions.
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http://dx.doi.org/10.1002/chem.202101250DOI Listing
May 2021

A preliminary study identifies early postoperative lung volume changes in patients with non-small cell lung cancer following video-assisted thoracic surgery using CT volumetry.

Mol Clin Oncol 2021 Jun 22;14(6):124. Epub 2021 Apr 22.

Department of Thoracic Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.

The present study aimed to investigate the changes in early postoperative lung volume in patients with non-small cell lung cancer (NSCLC) following video-assisted thoracic surgery (VATS) and to analyze the effects of the clinical characteristics on the lung volume of the patients. Therefore, 38 patients with NSCLC, who planned to undergo VATS at the Department of Thoracic Surgery, The Affiliated Hospital of Guizhou Medical University in June 2019, were enrolled into the present study. The clinical and computed tomography (CT) scan data from the patients was prospectively collected within 1 week preoperatively, and at 1, 3 and 6 months following surgery, then subsequently analyzed. A total of 34 patients successfully completed follow-up and were included in the datasets. The results showed that the volume of the right lung was larger compared with that in the left one, at each observational time point. The whole, right and left lung held the same trendline of volume changes, which was sharply decreased during the first postoperative month, increased quickly over the next 3 months, and slowly increased from months 3 to 6. There were 7 patients, whose whole lung volume was increased at 6 months following surgery compared with that preoperatively. In addition, significant differences were observed between males and females in the whole, right and left lung volume. However, the differences on the postoperative net expansion volume of the whole lung were not significant among sex, age, body mass index (BMI), smoking status and surgical side subgroups. The early changes of the postoperative lung volume were not linear, since the lung volume was significantly reduced during the first postoperative month, quickly increased in the next 3 months, and slowly increased from months 3 to 6. Sex, age, BMI, smoking status and surgical sides was not found to affect the postoperative volume and net expansion of the whole lung following VATS lobectomy.
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http://dx.doi.org/10.3892/mco.2021.2286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082225PMC
June 2021

[Effect of electroacupuncture on the expression of autophagy related protein in lung tissue of rats with chronic obstructive pulmonary disease].

Zhen Ci Yan Jiu 2021 Apr;46(4):266-71

Department of Physiology, College of Integrated Traditional Chinese and Western Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China; Institute of Acupuncture and Meridian, College of Acupuncture-moxibustion and Massage, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China.

Objective: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Feishu" (BL13) on the expression of autophagy related proteins in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), so as to explore the mechanism of EA underlying improvement of COPD.

Methods: Thirty male SD rats were randomly divided into normal, model and EA groups (=10 in each group). The COPD model was established by intratracheal infusion of Lipopolysaccharide (LPS, 1 mg/kg) and exposure in cigarette smoke. EA was applied to bilateral ST36 and BL13 for 30 min, once every other day for 2 weeks. The pulmonary function (forced vital capacity [FVC], forced expiratory volume in 0.1 s and 0.3 s [FEV0.1, FEV0.3], FEV0.1/FVC and FEV0.3/FVC) was detected by animal pulmonary function analysis system. Histopathological changes of the airway and lung were displayed by H.E. staining. Autophagosomes in the airway and lung tissues were observed by electron microscope. The expression of AMP activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Unc-51 like autophagy activating kinase 1(ULK1), autophagy related protein ATG6(Beclin1)mRNAs in lung tissue were examined by quantitative real-time PCR. The expression of AMPK, mTOR, ULK1, Beclin1 and microtubule-associated protein 1 light chain 3 (LC3)proteins in lung tissue were examined by Western blot. The contents of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the broncho alveolar lavage fluid (BALF) were assayed by ELISA.

Results: Following modeling, the FVC, FEV0.1, FEV0.3, FEV0.1/FVC and FEV0.3/FVC levels were significantly decreased (<0.01), the infiltration of inflammatory cells and the increase of autophagosomes were obvious in airway and lung tissue, the mRNA and protein expression of AMPK, ULK1, Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ were increased (<0.01), while the mRNA and protein expression of mTOR were decreased (<0.01), the contents of TNF-α and IL-6 in the BALF were increased in the model group compared with the normal group (<0.01). After EA intervention, all the indexes mentioned above were completely reversed in the EA group relevant to the model group (<0.01, <0.05).

Conclusion: EA at ST36 and BL13 can improve the lung function of COPD rats, which may be related to its effects in inhibiting the autophagy level and reducing the inflammation response in the lung.
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http://dx.doi.org/10.13702/j.1000-0607.201155DOI Listing
April 2021

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

Acta Pharmacol Sin 2021 Apr 30. Epub 2021 Apr 30.

Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11β-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11β-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11β-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 μmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2. Circulating 8 and M2, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11β-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.
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http://dx.doi.org/10.1038/s41401-021-00651-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086230PMC
April 2021

Implantable platinum nanotree microelectrode with a battery-free electrochemical patch for peritoneal carcinomatosis monitoring.

Biosens Bioelectron 2021 Apr 22;185:113265. Epub 2021 Apr 22.

Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, PR China. Electronic address:

As a severe stage of cancers, peritoneal carcinomatosis should be frequently monitored by means of ascites analysis. Nevertheless, the analysis process is traumatic and time-consuming in clinical practice. In this study, an implantable platinum nanotree microelectrode with a wireless, battery-free and flexible electrochemical patch was developed for in vivo and real-time peritoneal glucose detection to monitor peritoneal carcinomatosis. As the core of implantable microelectrode, platinum trees were synthesized by one-step electrodeposition method and highly sensitive to glucose detection. The platinum nanotree microelectrode was implantable in peritoneal cavity in minimally invasive way. A flexible circuit patch could execute electrochemical test and realize wireless power harvesting and data interaction with a near field communication (NFC)-enabled smartphone. The whole system could detect glucose dynamics in vivo in rat peritoneal cavity. Furthermore, the accuracy of this system was validated in ascites of patients. In this way, the system could offer hassle-free, rapid and minimally invasive opportunities toward peritoneal carcinomatosis monitoring.
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http://dx.doi.org/10.1016/j.bios.2021.113265DOI Listing
April 2021

Ebsulfur and Ebselen as highly potent scaffolds for the development of potential SARS-CoV-2 antivirals.

Bioorg Chem 2021 Apr 8;112:104889. Epub 2021 Apr 8.

Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, PR China. Electronic address:

The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (M) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 M by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074-0.91 μM. Notably, the molecules containing furane substituent displayed higher inhibition against M, followed by Ebselen 1i (IC = 0.074 μM) and Ebsulfur 2k (IC = 0.11 μM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to M, while molecular docking suggested that 2k formed an SS bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of M to combat COVID-19.
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http://dx.doi.org/10.1016/j.bioorg.2021.104889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026246PMC
April 2021

Recognition of chronic renal failure based on Raman spectroscopy and convolutional neural network.

Photodiagnosis Photodyn Ther 2021 Apr 26;34:102313. Epub 2021 Apr 26.

College of Software, Xinjiang University, Urumqi, 830046, Xinjiang, China; Key Laboratory of Signal Detection and Processing, Xinjiang University, Urumqi, 830046, Xinjiang, China.

Purpose: Chronic renal failure (CRF) is a disease with a high morbidity rate that can develop into uraemia, resulting in a series of complications, such as dyspnoea, mental disorders, hypertension, and heart failure. CRF may be controlled clinically by drug intervention. Therefore, early diagnosis and control of the disease are of great significance for the treatment and prevention of chronic renal failure. Based on the complexity of CRF diagnosis, this study aims to explore a new rapid and noninvasive diagnostic method.

Methods: In this experiment, the serum Raman spectra of samples from 47 patients with CRF and 53 normal subjects were obtained. In this study, Serum Raman spectra of healthy and CRF patients were identified by a Convolutional Neural Network (CNN) and compared with the results of identified by an Improved AlexNet. In addition, different amplitude of noise were added to the spectral data of the samples to explore the influence of a small random noise on the experimental results.

Results: A CNN and an Improved AlexNet was used to classify the spectra, and the accuracy was 79.44 % and 95.22 % respectively. And the addition of noise did not significantly interfere with the classification accuracy.

Conclusion: The accuracy of CNN of this study can be as high as 95.22 %, which greatly improves its accuracy and reliability, compared to 89.7 % in the previous study. The results of this study show that the combination of serum Raman spectrum and CNN can be used in the diagnosis of CRF, and small random noise will not cause serious interference to the data analysis results.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102313DOI Listing
April 2021

Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase.

Front Pharmacol 2021 12;12:600296. Epub 2021 Apr 12.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, School of Pharmaceutical Sciences, Health Science Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.

Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth . The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was -17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC.
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http://dx.doi.org/10.3389/fphar.2021.600296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072669PMC
April 2021

The inhibitory effects of the antifouling compound Irgarol 1051 on the marine diatom Skeletonema sp. across a broad range of photosynthetically active radiation.

Environ Sci Pollut Res Int 2021 Apr 28. Epub 2021 Apr 28.

College of Marine Science and Fisheries, Jiangsu Ocean University, Lianyungang, 222005, China.

The release of anthropogenic organic pollutants has resulted in extensive environmental risks to coastal waters. Among pollutants released, the most common antifoulant, Irgarol 1051, is an effective inhibitor of photosystem II of photoautotrophs; thus, the continuous release of this compound into surrounding seawater would potentially threaten marine algae. To investigate this, we grew the model marine diatom Skeletonema sp. at different concentrations of Irgarol 1051 and levels of photosynthetically active radiation (PAR). Irgarol did not affect the photochemical capacity when cells were incubated in the dark, but photochemical yields all significantly decreased, and relative inhibition by Irgarol increased once cells were exposed to even the lowest PAR, with lower photochemical yields observed under increased level of Irgarol. In addition, the rate of decrease in yield increased with Irgarol concentration but was unchanged among PAR treatments. The growth rates showed a similar pattern to photochemical yields, with lower values under higher Irgarol concentrations, but with no significant differences in the effect of Irgarol observed between the light levels employed. The ratio of repair to damage rates of PSII clearly shows that this ratio decreased with light intensity, largely due to increases in damage rates and that the PAR level at which repair balanced damage decreased under a high level of Irgarol. Our results suggest that the inhibitory effects of Irgarol become obvious after PAR exposure even at a relatively low light level, suggesting that Irgarol would affect phytoplankton throughout the daytime, and may therefore have a broad environmental risk, potentially limiting coastal primary production.
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http://dx.doi.org/10.1007/s11356-021-14135-7DOI Listing
April 2021

Dexmedetomidine protects SH-SY5Y cells against MPP -induced declining of mitochondrial membrane potential and cell cycle deficits.

Eur J Neurosci 2021 Apr 27. Epub 2021 Apr 27.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Dexmedetomidine (Dex), an adrenergic α2 receptor agonist, is commonly used in deep-brain stimulation surgery for Parkinson's disease (PD). However, there is evidence that the use of anesthetics may accelerate the progression of neurodegenerative diseases. The effect of Dex on PD remains unclear. Here, we cultured the all-trans-retinoicacid (ATRA) differentiated SH-SY5Y cells in vitro and then treated with MPP (1.5mM) with or without Dex (10nM) or Dex combined with Atipamezole (Ati,100nM, adrenergic α2 receptor inhibitor). The ratio of apoptotic cells, mitochondrial membrane potential (Δψm), reactive oxygen species (ROS), cell cycle and apoptotic markers (Cleaved caspase-3, 9) were analyzed by flow cytometry and immunofluorescence. We found that the levels of apoptotic ratio and cleaved caspase-3, 9 increased, ROS accumulated, and mitochondrial membrane potential decreased after MPP+ treatment, while these changes were partially reversed by Dex. Dex also prevented MPP induced cell arrest by increasing G1 phase cells, decreasing S phase cells, and decreasing the expression of cyclinD1 and Cdk4. Moreover, the effects of Dex were partially reversed by Ati. These findings reveal that Dex attenuated MPP -induced apoptosis of SH-SY5Y cells by preventing the loss of Δψm, reducing ROS, and regulating the cell cycle. Our findings indicated that Dex is more likely to be a potential drug for the treatment of PD.
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http://dx.doi.org/10.1111/ejn.15252DOI Listing
April 2021

Human serum mid-infrared spectroscopy combined with machine learning algorithms for rapid detection of gliomas.

Photodiagnosis Photodyn Ther 2021 Apr 23:102308. Epub 2021 Apr 23.

College of Information Science and Engineering, Xinjiang University, Urumqi 830046, China; College of Software, Xinjiang University, Urumqi 830046, China; Key Laboratory of signal detection and processing, Xinjiang University, Urumqi 830046, China. Electronic address:

In recent years, glioma has become one of the main diseases threatening human health, with a low cure rate and a high mortality rate. Therefore, correct diagnosis and treatment are essential for patients. This research aims to use mid-infrared spectroscopy combined with machine learning algorithms to identify patients with glioma. The glioma infrared spectra and the control group serum are smoothed and normalized, then the principal component analysis (PCA) algorithm is used to reduce the data dimensionality, and finally, the particle swarm optimization-support vector machine (PSO-SVM), backpropagation (BP) neural network and decision tree (DT) model are established. The classification accuracy of the three models was 92.00%, 91.83%, 87.20%, and the AUC values were 0.919, 0.945, and 0.866, respectively. The results show that PCA-PSO-SVM has a better classification effect. This study shows that mid-infrared spectroscopy combined with machine learning algorithms has great potential in the application of non-invasive, rapid and accurate identification of glioma patients.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102308DOI Listing
April 2021

Emergence of additional drug resistance during treatment of multidrug-resistant tuberculosis in China: a prospective cohort study.

Clin Microbiol Infect 2021 Apr 22. Epub 2021 Apr 22.

Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China. Electronic address:

Objectives: Little is known about how additional second-line drug resistance emerges during multidrug resistant tuberculosis(MDR-TB) treatment. The present study aimed to investigate the influence of microevolution, exogenous reinfection and mixed-infection on second-line drug resistance during the recommended two-year MDR-TB treatment.

Methods: MDR-TB patients were enrolled between 2013-2016 in a multi-centre prospective observational cohort study and followed for two years until treatment completion. Whole genome sequencing (WGS) was applied for serial Mycobacterium tuberculosis isolates from study participants throughout the treatment, to study the role of microevolution, exogenous reinfection and mixed-infection in the development of second-line drug resistance.

Results: Of the 286 enrolled MDR-TB patients, 63(22.0%) Mycobacterium tuberculosis isolates developed additional drug resistance during MDR-TB treatment, including 5(1.7%) that fulfilled the criteria of extensively drug-resistant TB. By comparing WGS data of serial isolates retrieved from the patients throughout treatment, 41(65.1%) of the cases of additional second-line drug resistance were due to exogenous reinfection, 18(28.6%) were caused by acquired drug resistance, i.e. microevolution, while the remaining 4(6.3%) were caused by mixed-infections with drug-resistant and drug-susceptible strains. In multivariate analysis, previous TB treatment[adjusted hazard ratio(aHR)2.51, 95% confidence interval(CI)1.51-4.18], extensive disease on chest X-ray(aHR3.39, 95%CI2.03-5.66) and type 2 diabetes mellitus (aHR4.00, 95%CI2.22-7.21) were independent risk factors associated with the development of additional second-line drug resistance.

Conclusions: A large proportion of additional second-line drug resistance emerging during MDR-TB treatment was attributed to exogenous reinfection, indicating the urgency of infection control in health facilities as well as the need of repeated drug susceptibility testing throughout MDR-TB treatment.
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http://dx.doi.org/10.1016/j.cmi.2021.04.001DOI Listing
April 2021

Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.

Lancet Digit Health 2021 05;3(5):e317-e329

Peking Union Medical College Hospital, Beijing, China.

Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability.

Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China.

Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959-0·977) or higher for myopic macular degeneration and 0·913 (0·906-0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957-0·994] for myopic macular degeneration and 0·973 [0·941-0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries.

Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine.

Funding: None.
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http://dx.doi.org/10.1016/S2589-7500(21)00055-8DOI Listing
May 2021

Gut-restricted apical sodium-dependent bile acid transporter inhibitor attenuates alcohol-induced liver steatosis and injury in mice.

Alcohol Clin Exp Res 2021 Apr 22. Epub 2021 Apr 22.

Harold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

Background: Recent studies revealed that human and experimental alcohol-related liver disease (ALD) is robustly associated with dysregulation of bile acid homeostasis which may in turn modulate disease severity. Pharmacological agents targeting bile acid metabolism and signaling may be potential therapeutics for treating ALD.

Methods: The potential beneficial effects of a gut-restricted apical sodium-dependent bile acid transporter (ASBT) inhibitor are studied in a chronic-plus-binge ALD mouse model.

Results: Here we report that blocking intestinal bile acid re-absorption by a gut-restricted ASBT inhibitor GSK2330672 attenuated hepatic steatosis and liver injury in a chronic-plus-binge ALD mouse model. Alcohol feeding is associated with intestinal bile acid accumulation but paradoxically impaired ileal farnesoid x receptor (FXR) function, and repressed hepatic cholesterol 7α-hydrolase (CYP7A1) expression despite decreased hepatic small heterodimer partner (SHP) and ileal fibroblast growth factor 15 (FGF15) expression. ASBT inhibitor treatment decreases intestinal bile acid accumulation and increases hepatic CYP7A1 expression, but further decreases ileal FXR activity. Alcohol feeding induces serum bile acid concentration that strongly correlates with liver injury marker. However, alcohol-induced serum bile acid elevation is not due to intrahepatic bile acid accumulation but is strongly and positively associated with hepatic multidrug resistance-associated protein 3 (MRP4) and MRP4 induction but poorly associated with sodium-taurocholate co-transporting peptide (NTCP) expression. ASBT inhibitor treatment decreases serum bile acid concentration without affecting hepatocyte basolateral bile acid uptake and efflux transporters.

Conclusion: We report that ASBT inhibitor treatment corrects alcohol-induced bile acid dysregulation and attenuates liver injury in experimental ALD.
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http://dx.doi.org/10.1111/acer.14619DOI Listing
April 2021

Ordered clustering of single atomic Te vacancies in atomically thin PtTe promotes hydrogen evolution catalysis.

Nat Commun 2021 Apr 21;12(1):2351. Epub 2021 Apr 21.

SZU-NUS Collaborative Center and International Collaborative Laboratory of 2D Materials for Optoelectronic Science and Technology of Ministry of Education, Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen, Guangdong, China.

Exposing and stabilizing undercoordinated platinum (Pt) sites and therefore optimizing their adsorption to reactive intermediates offers a desirable strategy to develop highly efficient Pt-based electrocatalysts. However, preparation of atomically controllable Pt-based model catalysts to understand the correlation between electronic structure, adsorption energy, and catalytic properties of atomic Pt sites is still challenging. Herein we report the atomically thin two-dimensional PtTe nanosheets with well-dispersed single atomic Te vacancies (Te-SAVs) and atomically well-defined undercoordinated Pt sites as a model electrocatalyst. A controlled thermal treatment drives the migration of the Te-SAVs to form thermodynamically stabilized, ordered Te-SAV clusters, which decreases both the density of states of undercoordinated Pt sites around the Fermi level and the interacting orbital volume of Pt sites. As a result, the binding strength of atomically defined Pt active sites to H intermediates is effectively reduced, which renders PtTe nanosheets highly active and stable in hydrogen evolution reaction.
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http://dx.doi.org/10.1038/s41467-021-22681-4DOI Listing
April 2021

Quality of opioid prescribing in older adults with or without Alzheimer disease and related dementia.

Alzheimers Res Ther 2021 Apr 12;13(1):78. Epub 2021 Apr 12.

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, 1225 Center Drive, Health Professions Nursing Pharmacy Building, Room 3321, Gainesville, FL, 32610, USA.

Background: Pain is common among individuals with Alzheimer's disease and related dementias (ADRD), and use of opioids has been increasing over the last decade. Yet, it is unclear to what extent opioids are appropriately prescribed for patients with ADRD and whether the appropriateness of opioid prescribing differs by ADRD status. The objective of this study is to compare the quality of opioid prescribing among patients with or without ADRD who have chronic noncancer pain.

Methods: A nationally representative cohort study of Medicare beneficiaries aged 50 years or older who had chronic pain but who had no cancer, hospice, or palliative care from 2011 to 2015. Four indicators of potentially inappropriate opioid prescribing were measured in patients residing in communities (75,258 patients with and 435,870 patients without ADRD); five indicators were assessed in patients in nursing homes (NHs) (37,117 patients with and 5128 patients without ADRD). Each indicator was calculated as the proportion of eligible patients with inappropriate opioid prescribing in the year after a chronic pain diagnosis. Differences in proportions between ADRD and non-ADRD groups were estimated using a generalized linear model adjusting for covariates through inverse probability weighting.

Results: Patients with ADRD versus those without had higher concurrent use of opioids and central nervous system-active drugs (community 44.1% vs 33.3%; NH 58.8% vs 54.1%, both P < 0.001) and no opioids or scheduled pain medications for moderate or severe pain (NH 60.1% vs 52.5%, P < 0.001). The ADRD versus non-ADRD group had higher use of long-term opioids for treating neuropathic pain in communities (21.7% vs 19.5%, P = 0.003) but lower use in NHs (26.9% vs 36.0%, P < 0.001). Use of strong or high-dose opioids when naive to opioids (community 1.5% vs 2.8%; NH 2.5% vs 3.5%) and use of contraindicated opioids (community 0.08% vs 0.12%; NH 0.05% vs 0.21%) were rare for either group.

Conclusion: Potential inappropriate opioid prescribing in 2 areas of pain care was more common among patients with ADRD than among patients without ADRD in community or NH settings. Further studies aimed at understanding the factors and effects associated with opioid prescribing patterns that deviate from guidelines are warranted.
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http://dx.doi.org/10.1186/s13195-021-00818-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061026PMC
April 2021

Transcatheter arterial embolization for hemorrhage after gynecologic hysterectomy: a multicenter study.

Acta Radiol 2021 Apr 20:2841851211010395. Epub 2021 Apr 20.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul, Republic of Korea.

Background: Transcatheter arterial embolization (TAE) is not common for hemorrhagic complications after gynecologic hysterectomy.

Purpose: To evaluate the effectiveness and safety of TAE for hemorrhage after hysterectomy for gynecologic diseases.

Material And Methods: This is a retrospective, multicenter study, which investigated 11 patients (median age = 45 years) who underwent TAE for hemorrhage after gynecologic hysterectomy between 2004 and 2020.

Results: The median interval between surgery and angiography was one day (range = 0-82 days). Hemodynamic instability and massive transfusion were present in 6 (54.5%) and 4 (36.4%) patients, respectively. CT scans (n = 7) showed contrast extravasation (n = 5), pseudoaneurysm (n = 1), or both (n = 1). On angiography, the bleeding arteries were the anterior division branches of the internal iliac artery (IIA) (n = 6), posterior division branch (lateral sacral artery, n = 1), and inferior epigastric artery (n = 1) in eight patients with active bleeding. In the remaining three patients, angiographic staining without active bleeding foci was observed at the vaginal stump, and the feeders for staining were all anterior division branches of the IIA. Technical and clinical success rates were 100% and 90.9% (10/11), respectively. In one patient, active bleeding focus was successfully embolized on angiography, but surgical hemostasis was performed for suspected bleeding on exploratory laparotomy. Postembolization syndrome occurred in one patient.

Conclusions: TAE is effective and safe for hemorrhage after hysterectomy for gynecologic diseases. Angiographic findings are primarily active bleeding, but angiographic staining is not uncommon. A bleeding focus is possible in any branch of the IIA, as well as the arteries supplying the abdominal wall.
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http://dx.doi.org/10.1177/02841851211010395DOI Listing
April 2021

Microconvex Dot-Featured Silk Fibroin Films for Promoting Human Umbilical Vein Endothelial Cell Angiogenesis via Enhancing the Expression of bFGF and VEGF.

ACS Biomater Sci Eng 2021 Apr 20. Epub 2021 Apr 20.

Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Insufficient vascularization of grafts often leads to delayed tissue ingrowth and impaired tissue function in tissue engineering. The surface topography of grafts plays critical roles in angiogenesis. In the present study, we prepared silk fibroin (SF)-based microtopography films with the number of convex dots ranging from 37 to 4835/mm. The convex dot-featured topography surfaces were characterized by scanning electron microscopy, a Profilm3D optical profilometer, atomic force microscopy, and a contact angle goniometer. The effect of microtopographic films on the proliferation, adhesion, and expression of angiogenic factors of human umbilical vein endothelial cells (HUVECs) was investigated. Our results demonstrated that the SF film surface with 2899 convex dots/mm significantly enhanced adhesion, viability, and levels of vascular endothelial growth factors and basic fibroblast growth factors of HUVECs and significantly downregulated the level of α-SMA in human aortic smooth muscle cells, indicating that the microtopographic films could promote angiogenesis. Furthermore, in vitro results showed that HUVEC proliferation was positively correlated with yes-associated protein (YAP) activation, suggesting that the enhanced angiogenesis was mediated via the YAP pathway. Finally, mice subcutaneous embedding model results indicated that the SF film surface with 2899 convex dots/mm could significantly enhance angiogenesis in vivo. Altogether, our results showed that the SF film surface with 2899 convex dots/mm promoted the angiogenesis of HUVECs and offered a novel angiogenesis-promoting strategy of implant surface design for tissue engineering.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01647DOI Listing
April 2021

Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

School of Life Sciences, Tianjin University, Tianjin, 300072, China;

Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP5), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP5 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.
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http://dx.doi.org/10.1073/pnas.2022269118DOI Listing
April 2021

Effect of different structural flaxseed lignans on the stability of flaxseed oil-in-water emulsion: An interfacial perspective.

Food Chem 2021 Apr 8;357:129522. Epub 2021 Apr 8.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan 430062, China. Electronic address:

The influences of the different structural flaxseed lignans on flaxseed oil (FO) emulsions during storage and digestion were investigated, focusing on their interfacial behavior. From perspective of interface, more than 60% of secoisolariciresinol (SECO) and the acidic hydrolysates of flaxseed lignan macromolecule (FLEH) were located on the interface of FO emulsions. It improved the stability of FO emulsions both during storage and digestion by inhibiting of free radical penetration and improving their targeted antioxidative activity. By comparison, the secoisolariciresinol diglucoside (SDG) and the alkaline hydrolysates of flaxseed lignan macromolecule (FLE) largely located in the aqueous and exerted lower antioxidative efficiency in emulsions. Moreover, SDG, SECO, FLE and FLEH slowed down the digestive rate of FO in emulsions, which might be due to flaxseed lignans inhibited the activity of digestive enzymes. These findings suggested that the different structural flaxseed lignans had the potential as antioxidants in emulsions during storage and digestion.
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http://dx.doi.org/10.1016/j.foodchem.2021.129522DOI Listing
April 2021

Characterisation of Staphylococcus aureus isolates from bovine mastitis in Ningxia, Western China.

J Glob Antimicrob Resist 2021 Apr 15;25:232-237. Epub 2021 Apr 15.

College of Agriculture, Ningxia University, Ningxia 750021, China. Electronic address:

Objectives: The aim of this study was to explore the antimicrobial resistance, virulence genes and molecular characteristics of Staphylococcus aureus from bovine mastitis cases.

Methods: A total of 125 non-duplicate S. aureus isolates from bovine mastitis cases in Ningxia, China, were characterised by antimicrobial susceptibility and molecular testing to determine the antimicrobial resistance, virulence genes and molecular characteristics.

Results: All methicillin-resistant S. aureus (MRSA) isolates were resistant to ampicillin, oxacillin, ceftiofur, erythromycin, gentamicin and clindamycin, with resistance to nine different categories of antibiotics observed amongst the MRSA isolates. Of the methicillin-susceptible S. aureus (MSSA) isolates, 62.1% were resistant to ampicillin and sulfisoxazole. Nine clonal complexes (CCs) and 16 spa types were identified by multilocus sequence typing (MLST) and spa typing. The dominant CCs were CC97 (51.2%) and CC50 (30.4%), while t224 (30.4%), t518 (20.0%) and t359 (16.8%) were the most common spa types. A relatively high proportion (27.2%) of the S. aureus isolates belonged to ST4053, a novel sequence type identified in this study. In addition, two CC30 MSSA isolates and two CC59 MRSA isolates were positive for Panton-Valentine leukocidin, while one CC239 MRSA isolate and three CC5 MSSA isolates were positive for TSST-1. All MRSA isolates carried the immune evasion cluster (IEC) genes, including scn (100%; 9/9) and sak (100%; 9/9), which were classified into type E.

Conclusion: Our study indicates severe antibiotic resistance and complicated molecular characterisation of S. aureus causing bovine mastitis. Additional studies should be conducted to monitor infection and transmission of S. aureus.
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http://dx.doi.org/10.1016/j.jgar.2021.03.021DOI Listing
April 2021

Dipyridyl-substituted thiosemicarbazone as a potent broad-spectrum inhibitor of metallo-β-lactamases.

Bioorg Med Chem 2021 May 8;38:116128. Epub 2021 Apr 8.

Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, PR China. Electronic address:

To combat the superbug infection caused by metallo-β-lactamases (MβLs), a dipyridyl-substituted thiosemicarbazone (DpC), was identified to be the broad-spectrum inhibitor of MβLs (NDM-1, VIM-2, IMP-1, ImiS, L1), with an IC value in the range of 0.021-1.08 µM. It reversibly and competitively inhibited NDM-1 with a K value of 10.2 nM. DpC showed broad-spectrum antibacterial effect on clinical isolate K. pneumonia, CRE, VRE, CRPA and MRSA, with MIC value ranged from 16 to 32 µg/mL, and exhibited synergistic antibacterial effect with meropenem on MβLs-producing bacteria, resulting in a 2-16-, 2-8-, and 8-fold reduction in MIC of meropenem against EC-MβLs, EC01-EC24, K. pneumonia, respectively. Moreover, mice experiments showed that DpC also had synergistic antibacterial action with meropenem. In this work, DpC was identified to be a potent scaffold for the development of broad-spectrum inhibitors of MβLs.
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http://dx.doi.org/10.1016/j.bmc.2021.116128DOI Listing
May 2021

Anaerobic biodegradation of soybean-process wastewater: Operation strategy and sludge bed characteristics of a high-performance Spiral Symmetric Stream Anaerobic Bioreactor.

Water Res 2021 Jun 31;197:117095. Epub 2021 Mar 31.

College of Environmental Science and Engineering, Donghua University, Shanghai 201620, China.

A 300m/d demonstration project of soybean-process wastewater has been established recently with a Spiral Symmetric Stream Anaerobic Bioreactor (SSSAB) as the core. In order to obtain the optimal operation strategy for a full-scale SSSAB and to make it run efficiently and stably in a demonstration project, a Pilot-scale SSSAB (P-SSSAB, effective volume 100 L) was performed for the treatment of soybean-process wastewater over 216 days. The volumetric load rate (VLR) range of the P-SSSAB was 0.32~27.17 kg COD/(m·d), where the highest VLR [27.17 kg COD/(m·d)] was 2.01 times to the highest value [13.5 kg COD/(m·d)] reported. The pH and VFA/ALK of the effluent from the P-SSSAB were in the range of 6.9 up to 9.2 and 0.03 up to 0.17, respectively. The methane yield of the P-SSSAB increased from 0.03 m/kg COD to 0.47 m/kg COD, which was 3.36 times to the maximum value (0.14 m/kg COD) reported. To meet the influent requirement of the aerobic biological treatment in demonstration project (influent COD ≤ 1.5 g/L), the maximum VLR of SSSAB was optimal at about 22 kg COD/(m·d). By analyzing the sludge bed characteristics of the P-SSSAB, it was obvious that zone I (the bottom of the bed) was the major contributor of the COD removal, while zone III (the upper part of the bed) was the major contributor for the NH-N increase. The anaerobic granular sludge (AGS) in the bed showed a good granulation. The average MLVSS/MLSS value in sludge bed was about 0.7, and PN/PS in TB-EPS (zone I, II and III) increased to 6.830, 4.257, and 3.747, respectively. SMA and coenzyme F values of zone III were the maximum [666.35 ml CH/(g VSS·d) and 0.690 mol/g VSS, respectively]. According to the analysis obtained from the 16S rRNA high-throughput sequencing, the microbial community in the AGS had been more specific to the soybean-process wastewater since the bacteria Firmicutes were increased. The relative abundance of microbe which perform direct interspecies electron transfer (DIET) for the syntrophic degradation of VFAs and production of the methane has been increased significantly, such as the bacteria Syntrophomonas and archaea Methanosaeta.
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http://dx.doi.org/10.1016/j.watres.2021.117095DOI Listing
June 2021

A randomized, controlled clinical trial of autologous stromal vascular fraction cells transplantation to promote mechanical stretch-induced skin regeneration.

Stem Cell Res Ther 2021 Apr 15;12(1):243. Epub 2021 Apr 15.

Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizhaoju Road, Shanghai, 200011, People's Republic of China.

Background: The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration.

Methods: This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks.

Results: The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI - 1.43 to - 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI - 1.30 to - 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI - 0.80 to - 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI - 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI - 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI - 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred.

Conclusions: Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue.

Trial Registration: This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020-retrospectively registered).
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http://dx.doi.org/10.1186/s13287-021-02318-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048343PMC
April 2021

L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4.

PLoS One 2021 15;16(4):e0250126. Epub 2021 Apr 15.

College of Animal Sciences, Zhejiang University, Hangzhou, China.

Amino acid metabolism plays an important role in controlling blood pressure by regulating the production of NO and ROS. The present study examined amino acid levels in the serum of Dahl SS rats and SS.13BN rats fed a low or high salt diet. We observed that 8 of 27 amino acids responded to a high salt diet in SS rats. Thus, we hypothesized that a defect in amino acids may contribute to the development of salt-induced hypertension. L-phenylalanine was used to treat SS rats with a low or high salt diet. The results demonstrated that L-phenylalanine supplementation significantly enhanced the serum nitrite levels and attenuated the high salt-induced hypertension in SS rats. Low levels of BH4 and nitrite and the impaired vascular response to acetylcholine were rescued by L-phenylalanine supplementation. Moreover, increased GTP cyclohydrolase (GCH1) mRNA, levels of BH4 and nitrite, and reduced superoxide production were observed in the kidneys of hypertensive SS rats with L-phenylalanine. The antihypertensive effects of L-phenylalanine might be mediated by enhancing BH4 biosynthesis and decreasing superoxide production from NO synthase, thereby protecting vascular and kidney function with reduced ROS and elevated NO levels. The present study demonstrated that L-phenylalanine supplementation restored vascular function, suggesting L-phenylalanine represented a potential target to attenuate high salt-sensitive hypertension through GCH1-BH4.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250126PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049246PMC
April 2021

Tumor-associated macrophages are associated with response to neoadjuvant chemotherapy and poor outcomes in patients with triple-negative breast cancer.

J Cancer 2021 15;12(10):2886-2892. Epub 2021 Mar 15.

Dept. of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Tumor-associated macrophages (TAMs) play an essential role in tumor progression and metastasis. However, the role of TAMs in neoadjuvant chemotherapy (NAC) is unclear and need to be identified. The main subject of this study was to investigate whether TAMs are related to the chemotherapeutic response with triple-negative breast cancers (TNBC). We retrospectively analyzed pretreatment tissue from patients who received NAC and followed by a mastectomy or breast-conservation for stage II-III TNBC in this study. The association between TAMs and the pathological complete response (pCR) rate of TNBC to NAC was analyzed. In addition, the correlation of the TAMs with recurrence-free survival (RFS) in patients with TNBC was also evaluated. Of the 91 patients, 31 (34.1%) patients experienced pathological complete response (pCR) after completion of NAC. Regarding the chemotheraptic response, patients with low infiltration of CD163 macrophages achieved a significantly higher rate of pCR. Importantly, Kaplan-Meier survival shown that patients with high infiltration of CD163 macrophages and non-pCR had poor OS and RFS. our data showed that TAMs may predict chemotherapeutic response and can be used as a promising prognostic candidate for poor survival in TNBC patients treated with NAC.
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http://dx.doi.org/10.7150/jca.47566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040876PMC
March 2021

Thoracic endometriosis: a case report and review of the literature.

Ann Palliat Med 2021 Mar;10(3):3500-3503

Department of Thoracic Surgery, The Affiliated Hospital of Zunyi Medical University, Guizhou, China.

Thoracic endometriosis is characterized by the presence of normal functioning endometrial tissues in normal pleural, diaphragm, or lung parenchyma, and main clinical symptoms include pneumothorax, menstrual hemothorax, menstrual hemoptysis, and pulmonary nodules. Chest X-ray (CXR), computed tomography (CT), magnetic resonance imaging (MRI), bronchoscopy, and surgical biopsy could be applied to the diagnosis of TE. Both drug therapy and surgical treatment were widely used to treat this disease, but no theory was used to guide the choice of treatment options. This paper introduces a case of menstrual hemoptysis due to endometriosis, and the final surgical treatment was chosen. The patient recovered well postoperatively and reported no hemoptysis during 2 months of follow-up. Reexamination of the chest through CT showed no ground-glass lesions or pulmonary exudative lesions. We make the following recommendations for patient selection when considering a surgical approach to the treatment of TE. Patients for whom surgery should be considered are those who (I) do not respond to drug therapy or relapse once drug therapy is withdrawn, (II) cannot tolerate drug therapy or who may wish to get pregnant in the near future (III) have limited lesions which are able to be completely removed during surgery. Patients in whom surgery is not recommended include those who have extensive lesions which cannot be surgically removed, including those with diaphragm or pleural involvement as the diseased tissues must be completely removed to avoid recurrence, and those who are unfit for surgery.
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http://dx.doi.org/10.21037/apm-21-280DOI Listing
March 2021

Discovery of novel celastrol-triazole derivatives with Hsp90-Cdc37 disruption to induce tumor cell apoptosis.

Bioorg Chem 2021 Mar 27;111:104867. Epub 2021 Mar 27.

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address:

To enhance the disruption of Hsp90-Cdc37, we designed and synthesized a series (27) of CEL-triazole derivatives. Most of the target compounds showed enhanced anti-proliferative activity on four cancer cell lines (MDA-MB-231, MCF-7, HepG2 and A459). Among them, compound 6 showed the best anti-proliferation (IC = 0.34 ± 0.01 μM) on MDA-MB-231. Pharmacological studies had found that compound 6 showed a higher ability to disrupt Hsp90-Cdc37 interaction in cells and inhibited the expression of the key Hsp90-Cdc37 clients in a concentration-dependent manner. Further studies indicated that an enhanced covalent binding between compound 6 and thiols (cysteine) might be one of the reasons for the increased activity. Furthermore, compound 6 arrested cells in the G/G phase and induced tumor cell apoptosis significantly. Overall, for cancer treatment, compound 6 was worth further exploring.
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http://dx.doi.org/10.1016/j.bioorg.2021.104867DOI Listing
March 2021

One "misunderstood" health issue: demonstrating and communicating the safety of influenza a vaccination in pregnancy: a systematic review and meta-analysis.

BMC Public Health 2021 Apr 9;21(1):703. Epub 2021 Apr 9.

Department of Broadcasting and Television, School of Journalism and Information Communication, Huazhong University of Science and Technology, Wuhan, 430000, People's Republic of China.

Background: The American College of Obstetricians and Gynecologists (ACOG) makes certain recommendations including the annual influenza vaccination of pregnant and pre-pregnant women during influenza (flu) season with an inactivated influenza vaccine as soon as it becomes available. The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices in association with ACOG state that the vaccine is safe to be given any trimester during pregnancy. However, due to a lack of communication, the public is unaware of the effects of influenza A vaccination in pregnancy. Since this is a vital public health concern, we aimed to communicate with evidence, the safety of influenza A vaccination in pregnancy in order to improve the rate of influenza A vaccines in pregnant women.

Methods: This health communication issue was based on the impact of influenza vaccine on fetal outcomes. Therefore, a search was carried out through medical-based online databases including: Cochrane Central, EMBASE, Web of Science, MEDLINE, http://www.ClinicalTrials.gov , and Google scholar for relevant English-based publications. Adverse fetal outcomes were considered as the endpoints of this analysis. The most specific RevMan 5.3 (latest version) software was used to carry out this analysis. Risk ratios (RR) with 95% confidence intervals (CI) were involved in data and results representation and interpretation.

Results: A total number of 679, 992 pregnant women participated in this analysis. Based on this current analysis, premature/preterm birth (< 37 weeks) was significantly reduced in pregnant women who were vaccinated for influenza A (RR: 0.80, 95% CI: 0.69-0.92; P = 0.002) as compared to those women who were not vaccinated. Similarly, influenza A vaccination decreased the risk for very preterm birth (< 32 weeks) (RR: 0.70, 95% CI: 0.58-0.84; P = 0.0001). The risks for infants with low birth weight (RR: 0.71, 95% CI: 0.49-1.04; P = 0.08), very low birth weight (RR: 0.69, 95% CI: 0.23-2.11; P = 0.52) and infants small for gestational age (RR: 0.93, 95% CI: 0.83-1.05; P = 0.26) were not increased with the vaccine. Influenza A vaccination was not associated with increased risks of stillbirth (RR: 0.63, 95% CI: 0.38-1.03; P = 0.07), birth defects (RR: 0.67, 95% CI: 0.26-1.72; P = 0.41), admission to neonatal intensive care unit or Apgar score < 7 in 5 min.

Conclusion: Influenza vaccine is completely safe in pregnancy. It significantly lowers premature birth and is not associated with any serious adverse neonatal outcome. Hence, this important piece of information should be communicated and conveyed to all pregnant women, for a safer and healthier pregnancy. At last, this public health issue should further be addressed to the population through media and other communication means in order to improve the rate of influenza A vaccines in pregnant women for a healthier and more productive population.
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http://dx.doi.org/10.1186/s12889-021-10740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034177PMC
April 2021