Publications by authors named "S Yang"

33,910 Publications

Efficacy and Safety of Cone-Beam Computed Tomography-Derived Augmented Fluoroscopy Combined with Endobronchial Ultrasound in Peripheral Pulmonary Lesions.

Respiration 2021 Apr 12:1-9. Epub 2021 Apr 12.

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Background: The diagnostic yield of peripheral pulmonary lesions (PPLs) using radial endobronchial ultrasound (EBUS) remains challenging without navigation systems. Cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) represents a recently developed technique, and its clinical utility remains to be investigated.

Objectives: The aim of this study was to investigate the diagnostic yield of transbronchial biopsy (TBB) using a combination of CBCT-AF and radial EBUS.

Methods: We recruited consecutive patients with PPLs who underwent radial EBUS-guided TBB, with or without AF, between October 2018 and July 2019. Following propensity score 1:1 matching, we recorded the procedure-related data and measured their efficacy and safety.

Results: While 72 patients received EBUS-plus-AF, 235 patients received EBUS only. We included 53 paired patients following propensity score matching. The median size of lesions was 2.8 and 2.9 cm in the EBUS-plus-AF group and EBUS-only group, respectively. Diagnostic yield was higher in the former group (75.5 vs. 52.8%; p = 0.015). The diagnostic yield for the EBUS-plus-AF group was significantly higher for lesions ≤30 mm (73.5 vs. 36.1%; p = 0.002). Moreover, there was no significant difference in the complication rates (3.8 vs. 5.7%; p = 1.000). Twenty-four nodules (45.3%) were invisible by fluoroscopy in the EBUS-plus-AF group. All of them were identifiable on CBCT images and successfully annotated for AF. The mean radiation dose of total procedure, CBCT, and fluoroscopy was 19.59, 16.4, and 3.17 Gy cm2, respectively.

Conclusions: TBB using a combination of CBCT-AF and EBUS resulted in a satisfactory diagnostic yield and safety.
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http://dx.doi.org/10.1159/000515181DOI Listing
April 2021

A step towards glucose control with a novel nanomagnetic-insulin fordiabetes care.

Int J Pharm 2021 Apr 9:120587. Epub 2021 Apr 9.

Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada; School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200436, PR China. Electronic address:

Massive efforts have been devoted to insulin delivery for diabetes care. Achieving a long-term tight-regulated blood glucose level with a low risk of hypoglycemia remains a great challenge. In this study we propose a novel strategy to efficiently regulate insulin action after insulin is injected or released into patient body aiming to achieve better glycemic control, which is achieved by the administration of insulin-conjugated magnetic nanoparticles (MNPs-Ins). We show that the locomotion of MNPs-Ins can be controlled to reach a target site on an in vitro microfluidic platform, which may open a way to modulate the physiological effect of insulin in a remote-control manner. Most importantly, the in vivo blood glucose regulation of the MNPs-Ins was performed on diabetic mice to understand the glycemic control performance. The results showed that the MNPs-Ins can achieve a better glycemic control with longer effective drug duration while not causing hypoglycemia and a magnetic-modulated hypoglycemic dynamics. Moreover, the in vivo histochemistry experiments confirmed the good biocompatibility of MNPs-Ins. Along with our on-going research on the possibility of the recycle and reuse of the MNPs-Ins, the finding presented in this paper may manifest a fascinating potential in insulin delivery in the near future.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120587DOI Listing
April 2021

Photothermal treatment by PLGA-gold nanorod-isatin nanocomplexes under near-infrared irradiation for alleviating psoriasiform hyperproliferation.

J Control Release 2021 Apr 9. Epub 2021 Apr 9.

Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan. Electronic address:

Psoriasis is a chronic autoimmune skin disorder that involves keratinocyte hyperproliferation and inflammatory cell recruitment. A strategy to mitigate psoriatic lesions is to induce keratinocyte apoptosis for proliferation suppression. Herein we designed a nanoformulation capable of treating psoriasis via hyperthermia-induced apoptosis in response to near-infrared (NIR) irradiation. To this end, gold nanorods (GNRs) and isatin, which is an anti-inflammatory agent for synergizing antipsoriatic activity, were loaded into a poly (lactic-co-glycolic acid) (PLGA) matrix to form the nanocomplexes. The physicochemical and photothermal properties of the nanocomplexes were determined in terms of size, surface charge, NIR-absorbing feature, isatin release, keratinocyte uptake, and cytotoxicity. The nanocomplexes showed a spherical shape with an average size of about 180 nm. The GNR-loaded nanoparticles can efficiently convert NIR light at 0.42 W/cm into heat with an increased temperature of 10 °C. When combined with NIR exposure, the nanocomplexes were internalized into keratinocyte cytoplasm with an inhibition of keratinocyte viability to about 60%. Live/dead cell assay and flow cytometry confirmed that the nanocomplexes could serve as NIR-absorbers to specifically elicit keratinocyte apoptosis through caspase and poly ADP-ribose polymerase (PARP) pathways. The in vivo psoriasiform murine model indicated that the combined nanocomplexes and NIR inhibited epidermal hyperplasia and neutrophil infiltration. The overexpressed cytokines in the lesion could be recovered to normal baseline level after the photothermal management. The subcutaneous nanocomplexes remained in the skin for at least 5 days. The nanocomposites produced a negligible toxicity in the skin or liver of healthy mice. The photothermal nanosystems, as designed in this study, shed new light on the therapeutic approach against psoriasis.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.005DOI Listing
April 2021

N-Heterocyclic Carbene-Catalyzed Asymmetric Synthesis of Cyclopentenones.

Org Lett 2021 Apr 12. Epub 2021 Apr 12.

College of Chemistry, Fuzhou University, Fuzhou 350116, China.

N-Heterocyclic carbene-catalyzed asymmetric construction of cyclopentenones using enals and α-diketones is achieved, furnishing a series of highly functionalized cyclopentenones in a highly diastereo- and enantioselective manner. The protocol tolerates substrates with both aromatic and aliphatic groups, and further transformations of the products delivered a range of value-added molecules.
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http://dx.doi.org/10.1021/acs.orglett.1c00870DOI Listing
April 2021

Engineering Clostridium cellulovorans for highly selective n-butanol production from cellulose in consolidated bioprocessing.

Biotechnol Bioeng 2021 Apr 12. Epub 2021 Apr 12.

William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 W. Woodruff Avenue, Columbus, OH, 43210, USA.

Cellulosic n-butanol from renewable lignocellulosic biomass has gained increased interest. Previously, we have engineered Clostridium cellulovorans, a cellulolytic acidogen, to overexpress the bifunctional butyraldehyde/butanol dehydrogenase gene adhE2 from Clostridium acetobutylicum for n-butanol production from crystalline cellulose. However, butanol production by this engineered strain had a relatively low yield of ~0.22 g/g cellulose due to the co-production of ethanol and acids. We hypothesized that strengthening the carbon flux through the central butyryl-CoA biosynthesis pathway and increasing intracellular NADH availability in C. cellulovorans adhE2 would enhance n-butanol production. In this study, thiolase (thlA ) from Clostridium acetobutylicum and 3-hydroxybutyryl-CoA dehydrogenase (hbd ) from Clostridium tyrobutyricum were overexpressed in C. cellulovorans adhE2 to increase the flux from acetyl-CoA to butyryl-CoA. In addition, ferredoxin-NAD(P) oxidoreductase (fnr), which can regenerate the intracellular NAD(P)H and thus increase butanol biosynthesis, was also overexpressed. Metabolic flux analyses showed that mutants overexpressing these genes had a significantly increased carbon flux toward butyryl-CoA, which resulted in increased production of butyrate and butanol. The addition of methyl viologen as an electron carrier in batch fermentation further directed more carbon flux towards n-butanol biosynthesis due to increased reducing equivalent or NADH. The engineered strain C. cellulovorans adhE2-fnr -thlA -hbd produced n-butanol from cellulose at a 50% higher yield (0.34 g/g), the highest ever obtained in batch fermentation by any known bacterial strain. The engineered C. cellulovorans is thus a promising host for n-butanol production from cellulosic biomass in consolidated bioprocessing. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/bit.27789DOI Listing
April 2021

Effects of Tannic Acid on Antioxidant Activity and Ovarian Development in Adolescent and Adult Female Brandt's Voles.

Reprod Sci 2021 Apr 12. Epub 2021 Apr 12.

Department of College of Biological Science and Technology, Yangzhou University, Yangzhou, 225009, China.

It is well known that tannins can influence the reproduction of animals, but there is little research published to elucidate the mechanics of this phenomenon. The purpose of this study was to investigate the role of antioxidation in the influence of tannic acid on the ovarian development of Brandt's voles (Lasiopodomys brandtii), which is a species of prairie animal that feeds on plants containing tannins. Postnatal 4-week-old female Brandt's voles were treated with 0 (control), 0.3% (low dose), or 0.6% (high dose) tannic acid for 4 or 9 weeks (i.e., when they reached puberty [8 weeks] or sexual maturity [13 weeks], respectively). The results showed that in both adolescent and adult Brandt's voles, firstly, treatment with tannic acid produced a higher ovary coefficient (ratio of the weight of ovaries to body weight), a greater proportion of mature follicles, and an increased follicular diameter. Secondly, tannic acid increased the serum contents of luteinizing hormone, follicle-stimulating hormone, and serum estradiol. Thirdly, tannic acid elevated the levels of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase) and reduced the level of malondialdehyde. Therefore, it is suggested that tannic acid may promote the ovarian development of female Brant's voles by enhancing their antioxidant capacity.
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http://dx.doi.org/10.1007/s43032-021-00578-3DOI Listing
April 2021

Letter to the Editor: Endoscopic Versus Conventional Thyroid Surgery: A Comparison of Quality of Life, Cosmetic Outcomes and Overall Patient Satisfaction with Treatment.

World J Surg 2021 Apr 12. Epub 2021 Apr 12.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1007/s00268-021-06106-3DOI Listing
April 2021

Machine-Learning-Guided Discovery and Optimization of Additives in Preparing Cu Catalysts for CO Reduction.

J Am Chem Soc 2021 Apr 12. Epub 2021 Apr 12.

State Key Laboratory of Physical Chemistry of Solid Surfaces, iChem, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.

Discovery and optimization of new catalysts can be potentially accelerated by efficient data analysis using machine-learning (ML). In this paper, we record the process of searching for additives in the electrochemical deposition of Cu catalysts for CO reduction (CORR) using ML, which includes three iterative cycles: "experimental test; ML analysis; prediction and redesign". Cu catalysts are known for CORR to obtain a range of products including C (CO, HCOOH, CH, CHOH) and C (CH, CH, CHOH, CHOH). Subtle changes in morphology and surface structure of the catalysts caused by additives in catalyst preparation can lead to dramatic shifts in CORR selectivity. After several ML cycles, we obtained catalysts selective for CO, HCOOH, and C products. This catalyst discovery process highlights the potential of ML to accelerate material development by efficiently extracting information from a limited number of experimental data.
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http://dx.doi.org/10.1021/jacs.1c00339DOI Listing
April 2021

Prognostic values of treatment modalities on head and neck mucosal melanomas in elderly patients: a population-based analysis.

Ann Transl Med 2021 Mar;9(5):391

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Background: Head and neck mucosal melanoma (HNMM) is defined as a rare malignant tumor derived from melanocytes. There is no consensus regarding the treatment protocol for HNMM in elderly patients.

Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify elderly patients diagnosed with HNMM from 1975 to 2016. The chi-squared test was used to compare patient characteristics. The reverse Kaplan-Meier method was used to estimate the median follow-up time. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival (OS) and disease-specific survival (DSS) of the groups. Cox regression analysis was used to evaluate the risk factors for OS and DSS of HNMM.

Results: Our retrospective study included 828 elderly patients with HNMM, and the 5-year OS and DSS rates were 22.4% and 27.4%, respectively. After adjusting for other variables in multivariate analysis, patients undergoing radiotherapy alone had worse OS [hazard ratio (HR) =1.449, 95% confidence interval (CI): 1.010-1.742, P=0.006] and DSS (HR =1.656, 95% CI: 1.257-2.181, P<0.001) than those undergoing surgery alone. No significant difference in OS (HR =0.892, 95% CI: 0.753-1.056, P=0.183) or DSS (HR =0.917, 95% CI: 0.764-1.101, P=0.354) was observed for patients undergoing surgery with or without radiotherapy. Our analysis of the subgroup of patients with complete clinical staging information demonstrated that the effects of surgery alone on OS (HR =0.734, 95% CI: 0.562-0.958, P=0.023) were inferior to those of surgery with radiotherapy, but no significant difference was noted compared with radiotherapy alone.

Conclusions: The survival of elderly patients with HNMM is increased with the combination of surgery and radiotherapy compared with surgery alone and radiotherapy alone. In addition, the population-based analysis demonstrated that combination therapy exhibited an obviously increased usage rate from 1975 to 2016, representing a mainstream treatment modality.
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http://dx.doi.org/10.21037/atm-20-6021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033355PMC
March 2021

Machine Learning-Based Radiomics Nomogram for Detecting Extramural Venous Invasion in Rectal Cancer.

Front Oncol 2021 26;11:610338. Epub 2021 Mar 26.

Department of Diagnostic Radiology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Objective: To establish and validate a radiomics nomogram based on the features of the primary tumor for predicting preoperative pathological extramural venous invasion (EMVI) in rectal cancer using machine learning.

Methods: The clinical and imaging data of 281 patients with primary rectal cancer from April 2012 to May 2018 were retrospectively analyzed. All the patients were divided into a training set (n = 198) and a test set (n = 83) respectively. The radiomics features of the primary tumor were extracted from the enhanced computed tomography (CT), the T2-weighted imaging (T2WI) and the gadolinium contrast-enhanced T1-weighted imaging (CE-TIWI) of each patient. One optimal radiomics signature extracted from each modal image was generated by receiver operating characteristic (ROC) curve analysis after dimensionality reduction. Three kinds of models were constructed based on training set, including the clinical model (the optimal radiomics signature combining with the clinical features), the magnetic resonance imaging model (the optimal radiomics signature combining with the mrEMVI status) and the integrated model (the optimal radiomics signature combining with both the clinical features and the mrEMVI status). Finally, the optimal model was selected to create a radiomics nomogram. The performance of the nomogram to evaluate clinical efficacy was verified by ROC curves and decision curve analysis curves.

Results: The radiomics signature constructed based on T2WI showed the best performance, with an AUC value of 0.717, a sensitivity of 0.742 and a specificity of 0.621. The radiomics nomogram had the highest prediction efficiency, of which the AUC was 0.863, the sensitivity was 0.774 and the specificity was 0.801.

Conclusion: The radiomics nomogram had the highest efficiency in predicting EMVI. This may help patients choose the best treatment strategy and may strengthen personalized treatment methods to further optimize the treatment effect.
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http://dx.doi.org/10.3389/fonc.2021.610338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033032PMC
March 2021

Prenatal and postnatal exposure to Bisphenol A and Asthma: a systemic review and meta-analysis.

J Thorac Dis 2021 Mar;13(3):1684-1696

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: Bisphenol A (BPA) is a plasticizer with high production and ubiquitous usage in polycarbonate plastics and epoxy resins. The association between prenatal or postnatal exposure to BPA and childhood wheeze/asthma has not been well established. Our study aimed to provide further justification for the current studies.

Methods: Studies were searched from PubMed, Web of Science, Scopus and Embase from inception until Sep 15, 2020. Meta-analysis was performed to calculate pooled adjusted odds ratios (aOR). The methodological quality of included studies was assessed by using the Newcastle Ottawa Scale (NOS).

Results: Of 2,814 screened articles, 9 studies with 3,885 participants were included in the final analysis. When all studies were pooled, postnatal exposure to BPA was associated with a higher risk of childhood asthma (aOR =1.43; 95% CI: 1.28-1.59) or childhood wheeze (aOR =1.38; 95% CI: 1.18-1.62). Prenatal exposure to BPA had a small but significant increased risk of childhood asthma (aOR =1.17; 95% CI: 1.01-1.34). An increased risk of childhood wheeze was related to prenatal exposure to BPA at 16 weeks' gestation (aOR =1.29; 95% CI: 1.07-1.55), but not at 26 weeks' gestation (aOR =1.07; 95% CI: 0.88-1.29) nor at random-time gestation (aOR =1.02; 95% CI: 0.89-1.16).

Conclusions: Prenatal and postnatal exposure to BPA was related to an increased risk of childhood asthma. However, only postnatal and early gestational exposure (at 16 weeks) to BPA could induce the risk of childhood wheeze, but not late gestational exposure (at 26 weeks).
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http://dx.doi.org/10.21037/jtd-20-1550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024800PMC
March 2021

Curcumin promotes the survival of ischemic random skin flaps via autophagy.

Am J Transl Res 2021 15;13(3):1337-1351. Epub 2021 Mar 15.

Department of Burn and Wound Center, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, China.

Random skin flaps have been widely applied in reconstructive and plastic surgery; however, necrosis usually happens due to insufficient blood supply in the ischemic area of flaps. Curcumin (CUR) is a primary bioactive compound of turmeric (, L.), which has been proven to be effective on anticancer, decreasing oxidative stress and apoptosis through activating autophagy, and promoting angiogenesis in ischemic tissue. Therefore, the potential therapeutic effect of CUR on promoting survival of ischemic random skin flaps and its underlying mechanism associated with autophagy were investigated. After establishment of dorsal random skin flaps, sixty mice were randomly divided into three groups: Control, CUR or CUR+3-methyladenine (3-MA, an autophagy inhibitor). The results showed that CUR increased the viability area and blood flow as well as relieved the edema of skin flaps through promoting angiogenesis, decreasing oxidative stress, and inhibiting apoptosis of the ischemic area. Further study confirmed that CUR activated autophagy in the random skin flaps, and 3-MA effectively reversed the effect on viability, neovascularization, oxidative stress and apoptosis, suggesting autophagy played a vital role in these CUR's protective effect on random skin flaps. Moreover, this CUR-induced autophagy should be mediated through downregulating the PI3K/AKT/mTOR signaling pathway. Together with secondary response of increased angiogenesis, reduced oxidative stress and apoptosis, CUR effectively improved survival of random skin flaps in vivo. To sum up, our research showed the great potential of CUR using as a promising flap protective therapy for random skin flap survival and regeneration.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014401PMC
March 2021

suppresses cell growth via MET/STAT3 signaling in lung cancer.

Am J Transl Res 2021 15;13(3):1221-1232. Epub 2021 Mar 15.

School of Medicine, Southern University of Science and Technology Shenzhen 518055, China.

has been reported to be down-regulated in several cancers, but its expression pattern and roles in lung cancer is unclear. Given the crucial role of microRNAs in cancer progression, we examined the expression and function of in lung adenocarcinoma. expression in lung cancer tissues and cell lines was measured by qRT-PCR. Cell proliferation was measured by WST-1 and colony formation assays were used to reveal the role of in lung cancer . was notably down-regulated in lung cancer tissues as compared to normal lung tissues, but it was not associated with the clinical characteristics of tumor stage, differentiation and patient's smoking status. Colony formation ability and cell proliferation were suppressed by mimics in lung cancer cell lines. Mechanistically, mimics could reduce MET and STAT3 protein expression and induce apoptosis as measured by PARP protein. We conclude that may play a tumor suppressor role via inhibiting MET-STAT3 signaling and have potential to be a therapeutic target and biomarker in lung adenocarcinoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014426PMC
March 2021

Direct and Indirect Somatic Embryogenesis Induction in Abel.

Front Plant Sci 2021 26;12:644389. Epub 2021 Mar 26.

Key Laboratory of Forest Silviculture and Conservation of the Ministry of Education, The College of Forestry, Beijing Forestry University, Beijing, China.

Abel. is an important woody oil species; however, the shortage of rapid and industrialized seedling culture is a large constraint on the development of the tea oil industry. Somatic embryogenesis (SE) is one of the main powerful biotechnological tools for plant mass regeneration, but the largely unknown SE in limits the scale production of clonal plants. In this study, we described a high-efficiency SE system via direct and indirect pathways in and investigated the effect of genotype, explant age and phytohormones on SE. In the direct pathway, somatic embryos were highly induced from immature seeds 220 days after full blossom, and the development of embryoids was achieved with a combination of 0.19 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.05 mg/L thidiazuron (TDZ). In the indirect pathway, embryogenic calli were induced from the same explants in medium containing 1.5 mg/L 2,4-D, while 0.75 mg/L 2,4-D treatment led to high proliferation rates for embryogenic calli. The addition of 0.19 mg/L 2,4-D alone stimulated the production of globular embryos while causing a 75% loss of the induction rate in the heart embryo stage. Upon transfer of the globular embryos to phytohormone-free medium, an optimal induction rate of 62.37% from globular embryos to cotyledonary embryos was obtained. These data suggest that the subsequent differentiation process after the globular embryo stage in ISE is more similar to an endogenous phytohormones-driven process. Mature embryos germinated to produce intact plantlets on half-strength MS basal medium with a regeneration rate of 63.67%. Histological analysis confirmed the vascular bundle isolation of embryoids from the mother tissue. We further studied the different varieties and found that there were no significant genotype differences for SE induction efficiency in . Thus, we established a high-efficiency induction system for direct and indirect somatic embryogenesis (ISE) in and regenerated intact plantlets via SE, not organogenesis. ISE has a more complicated induction and regulatory mechanism than direct somatic embryogenesis. The improved protocol of SE would benefit mass propagation and genetic manipulation in .
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http://dx.doi.org/10.3389/fpls.2021.644389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034400PMC
March 2021

Dammarane Sapogenins Improving Simulated Weightlessness-Induced Depressive-Like Behaviors and Cognitive Dysfunction in Rats.

Front Psychiatry 2021 26;12:638328. Epub 2021 Mar 26.

Affiliated (T.C.M) Hospital, Sino-Portugal Traditional Chinese Medicine (TCM) International Cooperation Center, Southwest Medical University, Luzhou, China.

Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus.
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http://dx.doi.org/10.3389/fpsyt.2021.638328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032884PMC
March 2021

Oleuropein Attenuates Lipopolysaccharide-Induced Acute Kidney Injury and by Regulating Toll-Like Receptor 4 Dimerization.

Front Pharmacol 2021 24;12:617314. Epub 2021 Mar 24.

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.

Acute kidney injury (AKI) is a common critical illness that involves multiple systems and multiple organs with a rapid decline in kidney function over short period. It has a high mortality rate and presents a great treatment challenge for physicians. Oleuropein, the main active constituent of Hook. et Arn. var. kwangsiensis Hand.-Mazz. displays significant anti-inflammatory activity, although oleuropein's therapeutic effect and mechanism of action in AKI remain to be elucidated. The present study aimed to further clarify the mechanism by which oleuropein exerts effects on inflammation and . , the inflammatory effect and mechanism were investigated through ELISA, Western blotting, the thermal shift assay, co-immunoprecipitation, and immunofluorescence staining. Lipopolysaccharide (LPS) induced acute kidney injury was employed in an animal model to investigate oleuropein's therapeutic effect on AKI and mechanism . The underlying mechanisms were investigated by Western blot analysis of kidney tissue. In LPS-stimulated macrophages, our data demonstrated that oleuropein significantly reduced the expression of inflammatory mediators like NO, IL-6, TNF-α, iNOS, and COX-2. Moreover, oleuropein inhibited NF-κB/p65 translocation, and had a negative regulatory effect on key proteins in the NF-κB and MAPK pathways. In addition, the thermal shift and co-immunoprecipitation assays revealed that oleuropein played an essential role in binding to the active sites of TLR4, as well as inhibiting TLR4 dimerization and suppressing the binding of TLR4 to MyD88. Oleuropein markedly alleviated LPS induced acute kidney injury, decreased serum creatinine and blood urea nitrogen (BUN) levels and proinflammatory cytokines. More importantly, the TLR4-MyD88-NF-κB/MAPK pathways were confirmed to play an important role in the oleuropein treatment of AKI. In this study, oleuropein exhibited excellent anti-inflammatory effects by regulating TLR4-MyD88-NF-κB/MAPK axis and , suggesting oleuropein as a candidate molecule for treating AKI.
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http://dx.doi.org/10.3389/fphar.2021.617314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024564PMC
March 2021

The Usefulness of Diffusion Tensor Tractography in Diagnosing Neuropathic Pain: A Narrative Review.

Front Neurosci 2021 26;15:591018. Epub 2021 Mar 26.

Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu, South Korea.

Diffusion tensor tractography (DTT) is derived from diffusion tensor imaging. It has allowed visualization and estimation of neural tract injury, which may be associated with the pathogenesis of neuropathic pain (NP). The aim of the present study was to review DTT studies that demonstrated the relationship between neural injuries and NP and to describe the potential use of DTT in the evaluation of neural injuries that are involved in the pathophysiological process of NP. A PubMed search was conducted for articles published until July 3, 2020, which used DTT to investigate the association between neural injuries and NP. The key search phrase for identifying potentially relevant articles was (diffusion tensor tractography AND pain). The following inclusion criteria were applied for article selection: (1) studies involving patients with NP and (2) studies in which DTT was applied for the evaluation of NP. Review articles were excluded. Altogether, 108 potentially relevant articles were identified. After reading the titles and abstracts and assessment of eligibility based on the full-text articles, 46 publications were finally included in our review. The results of the included studies suggested that DTT may be beneficial in identifying the pathophysiological mechanism of NP of various origins including central pain caused by brain injuries, trigeminal neuralgia, sciatica, and some types of headache. Further studies are needed to validate the efficacy of DTT in investigating the pathophysiology of other types of NP.
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http://dx.doi.org/10.3389/fnins.2021.591018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032899PMC
March 2021

PB1 S524G mutation of wild bird-origin H3N8 influenza A virus enhances virulence and fitness for transmission in mammals.

Emerg Microbes Infect 2021 Apr 12:1-46. Epub 2021 Apr 12.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, 130122, China.

Influenza H3N8 viruses have been recovered frequently from wild bird species, including (primarily from migratory ducks) and (primarily from shorebirds). However, little attention has been given to the transmission ability of H3N8 avian influenza viruses among mammals. Here, we study the potential human health threat and the molecular basis of mammalian transmissibility of H3N8 avian influenza viruses isolated from wild bird reservoirs. We classified eight H3N8 viruses into seven different genotypes based on genomic diversity. Six of eight H3N8 viruses isolated naturally from wild birds have acquired the ability to bind to the human-type receptor. However, the affinity for α-2,6-linked SAs was lower than that for α-2,3-linked SAs. Experiments on guinea pigs demonstrated that three viruses transmitted efficiently to direct-contact guinea pigs without prior adaptation. Notably, one virus transmitted efficiently via respiratory droplets in guinea pigs but not in ferrets. We further found that the PB1 S524G mutation conferred T222 virus airborne transmissibility between ferrets. We also determined that the 524G mutant increased viral pathogenicity slightly in mice compared with the WT (wild type). Based on these results, we elucidated the potential human health threat and molecular basis of mammalian transmissibility of H3N8 influenza viruses. We emphasized the need for continued surveillance of the H3N8 influenza viruses circulating in birds.
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http://dx.doi.org/10.1080/22221751.2021.1912644DOI Listing
April 2021

Carbon nanotubes promote alveolar macrophages toward M2 polarization mediated epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation.

Nanotoxicology 2021 Apr 10:1-17. Epub 2021 Apr 10.

Department of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei, PR China.

With substantial progress of nanotechnology, carbon nanotubes (CNTs) are widely used in a variety of industrial and commercial applications. There is rising concern about potential adverse health effects, such as pulmonary fibrosis, related to inhalation of CNTs. The detailed cellular and molecular mechanisms of pulmonary fibrosis induced by CNTs are still not clear. Epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT) are considered as critical events in pathogenesis of pulmonary fibrosis. Alveolar macrophages (AMs) polarization plays a key role of regulating EMT and FMT in pulmonary fibrosis. In this study, we applied CNTs to stimulate primary mouse AMs under M1 or M2 polarization conditions, then analyzed the proportion of F4/80CD11c or F4/80CD206 AMs, mRNA expression and activities of iNOS or Arg-1, as well as mRNA expression and content of TNF-α and IL-6 or TGF-β and IL-10 to evaluate dynamic phenotypic and functional changes of AMs. Single-walled CNT (SWCNT), short-type multi-walled CNT (MWCNT), and long-type MWCNT exposure at dose of 50 µg/ml promote AMs polarization toward M1 phenotype at early stage, while promote AMs polarization toward M2 phenotype at late stage. The roles of AMs polarization during development of EMT and FMT were further investigated by conditioned medium (CM) experiments. CNTs-activated M2 AMs promote progression of EMT and FMT secreting TGF-β. Furthermore, up-regulating IRF4 may be involved in CNTs-induced M2 AMs polarization. In conclusion, this study demonstrates a new insight that CNTs exposure promotes AMs polarization toward M2 phenotype which facilitate EMT and FMT through secreting TGF-β.
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http://dx.doi.org/10.1080/17435390.2021.1905098DOI Listing
April 2021

Ultra-high performance supercritical fluid chromatography method for separation and quantitation of saikosaponins in herbal medicine.

J Pharm Biomed Anal 2021 Mar 26;199:114039. Epub 2021 Mar 26.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address:

Saikosaponins are the main active ingredients of Bupleuri Radix and have been shown to have hepatoprotective, immunomodulatory and anti-viral activities. Among the saikosaponins, saikosaponin a (SSa), saikosaponin b (SSb) and saikosaponin b (SSb) are a group of isomers, which are difficult to separate by HPLC. In this study, a new method for separation and quantitation of saikosaponins was established by using ultra-high performance supercritical fluid chromatography (UHPSFC). A Torus Diol column (100 mm × 3 mm, 1.7 μm) was applied in this study. The mobile phase CO (A) was the main solvent with MeOH (B) as co-solvent. The results showed that the five saikosaponins were successfully separated within 22 min through optimization of chromatographic conditions. Besides, the UHPSFC method was applied for the quantitation of saikosaponins in a patent medicine Chaihu Dropping Pills, and demonstrated a good correlation coefficient (R) ≥ 0.9990 in the range of 0.025 - 0.25 mg/mL. The recoveries of the five saikosaponins at three different concentrations were in the range of 90.23-99.84%. This study indicates that the proposed method has high separation efficiency in analyzing saikosaponins, which provides a new way for the separation and quantitation of saikosaponins in herbal medicines.
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http://dx.doi.org/10.1016/j.jpba.2021.114039DOI Listing
March 2021

Traditional Chinese exercise potential role as prevention and adjuvant therapy in patients with COVID-19.

Complement Ther Clin Pract 2021 Apr 2;43:101379. Epub 2021 Apr 2.

School of Acupuncture and Tuina /The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Sichuan, Chengdu, 610075, China. Electronic address:

The epidemic situation of COVID-19 is a great public health emergency worldwide characterized by fastest spreading, widest infection range and the mostly difficult to prevent and control in recent years. According to medical experience, traditional Chinese exercises (TCE) have been applied for COVID-19 prevention, adjuvant treatment or rehabilitation, and achieved some curative effects. They can enhance the body immunity, improve the function of organs, especially cardiopulmonary function, promote physical and mental rehabilitation by adjusting the body, regulating the breath, regulating the mind. This paper aims to investigate the potential value of TCE for health preservation in the prevention and adjuvant treatment for COVID-19 according to an overview of application and analysis of existing evidence. On this basis, this review proposed the TCE plan by visiting clinical and practice experts, so as to provide some references for the prevention and treatment of COVID-19 with TCE in the world.
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http://dx.doi.org/10.1016/j.ctcp.2021.101379DOI Listing
April 2021

Invasive Mucinous Adenocarcinomas with Spatially Separate Lung Lesions: Analysis of Clonal Relationship by Comparative Molecular Profiling.

J Thorac Oncol 2021 Apr 8. Epub 2021 Apr 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, USA. Electronic address:

Introduction: Pulmonary invasive mucinous adenocarcinomas (IMA) commonly present with spatially separate lung lesions. Clonal relationship between such lesions, particularly those involving contralateral lobes, is not well established. Here, we used comparative genomic profiling to address this question.

Methods: Patients with genomic analysis performed on 2 IMA located in different lung regions were identified. Molecular assays included DNA-based next-generation sequencing (NGS) for 410-468 genes (MSK-IMPACT), RNA-based NGS for 62 genes (MSK-Fusion), or non-NGS assays.

Results: Comparative genomic profiling was performed on 2 separate IMAs in 24 patients, of whom 19 had contralateral lesions. Tumors from all but one patient shared matching driver alterations, including KRAS (n=19), NRG1 (n=2), ERBB2 (n=1) or BRAF (n=1). In addition, in patients with paired tumors profiled by NGS (n=12), shared driver alterations were accompanied by up to 4 (average 2.6) other identical mutations, further supporting the clonal relationship between the tumors. Only in a single patient separate IMAs harbored entirely non-overlapping mutation profiles, supporting clonally unrelated, distinct primary tumors. Notably, in a subset of patients (n=3), molecular testing confirmed a clonal relationship between the original resected IMAs and subsequent contralateral IMA presenting after an extremely long latency (8.1-11.7 years).

Conclusions: Comparative molecular profiling supports that nearly all separate pulmonary IMA lesions represent intrapulmonary spread arising from a single tumor and documents a subset with a remarkably protracted course of intrapulmonary progression. This study reinforces the unique biology and clinical behavior of IMAs while further highlighting the value of genomic testing for clarifying the clonal relationship between multiple lung carcinomas.
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http://dx.doi.org/10.1016/j.jtho.2021.03.023DOI Listing
April 2021

A novel rosamine-based fluorescent probe for the rapid and selective detection of cysteine in BSA, water, milk, cabbage, radish, apple, and pear.

Food Chem 2021 Mar 23;356:129658. Epub 2021 Mar 23.

Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China. Electronic address:

A novel fluorescent probe (RA), based on the rosamine skeleton bearing acrylate group, has been reasonably designed and prepared, which employed an addition-cyclization-elimination sequence reaction mechanism to detect cysteine. RA displayed rapid response to cysteine within 1.5 min, and exhibited satisfactory selectivity for cysteine over HS, glutathione (Glu), and homocysteine (Hcy), due to the formation of seven-membered lactam favored kinetically. Fluorescence ratio was utilized to detect cysteine from 6.0 to 20.0 μM with a detection limit of 0.29 μM. More, RA was used to monitor cysteine in BSA, water, milk, milk powder, cabbage, radish, apple, and pear.
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http://dx.doi.org/10.1016/j.foodchem.2021.129658DOI Listing
March 2021

IHG-MA: Inductive heterogeneous graph multi-agent reinforcement learning for multi-intersection traffic signal control.

Neural Netw 2021 Mar 22;139:265-277. Epub 2021 Mar 22.

School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China. Electronic address:

Multi-agent deep reinforcement learning (MDRL) has been widely applied in multi-intersection traffic signal control. The MDRL algorithms produce the decentralized cooperative traffic-signal policies via specialized multi-agent settings in certain traffic networks. However, the state-of-the-art MDRL algorithms seem to have some drawbacks. (1) It is desirable that the traffic-signal policies can be smoothly transferred to diverse traffic networks, however, the adopted specialized multi-agent settings hinder the traffic-signal policies to transfer and generalize to new traffic networks. (2) Existing MDRL algorithms which are based on deep neural networks cannot flexibly tackle a time-varying number of vehicles traversing the traffic networks. (3) Existing MDRL algorithms which are based on homogeneous graph neural networks fail to capture the heterogeneous features of objects in traffic networks. Motivated by the above observations, in this paper, we propose an algorithm, referred to as Inductive Heterogeneous Graph Multi-agent Actor-critic (IHG-MA) algorithm, for multi-intersection traffic signal control. The proposed IHG-MA algorithm has two features: (1) It conducts representation learning using a proposed inductive heterogeneous graph neural network (IHG), which is an inductive algorithm. The proposed IHG algorithm can generate embeddings for previously unseen nodes (e.g., new entry vehicles) and new graphs (e.g., new traffic networks). But unlike the algorithms based on the homogeneous graph neural network, IHG algorithm not only encodes heterogeneous features of each node, but also encodes heterogeneous structural (graph) information. (2) It also conducts policy learning using a proposed multi-agent actor-critic(MA), which is a decentralized cooperative framework. The proposed MA framework employs the final embeddings to compute the Q-value and policy, and then optimizes the whole algorithm via the Q-value and policy loss. Experimental results on different traffic datasets illustrate that IHG-MA algorithm outperforms the state-of-the-art algorithms in terms of multiple traffic metrics, which seems to be a new promising algorithm for multi-intersection traffic signal control.
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http://dx.doi.org/10.1016/j.neunet.2021.03.015DOI Listing
March 2021

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study.

Eur J Prev Cardiol 2021 Apr;28(2):227-234

Clinical Laboratory of The Affiliated Cancer Hospital, Guangxi Medical University, China.

Background: Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction.

Methods: A two-sample Mendelian randomization study on disease was conducted, i.e. "coronary heart disease" (n = 184,305) and "acute myocardial infarction" (n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10-8, were used as an instrumental variable.

Results: None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction (p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923-1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932-1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy (p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction.

Conclusions: The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.
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http://dx.doi.org/10.1177/2047487319894679DOI Listing
April 2021

Inference of dynamic systems from noisy and sparse data via manifold-constrained Gaussian processes.

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

Department of Statistics, Harvard University, Cambridge, MA 02138

Parameter estimation for nonlinear dynamic system models, represented by ordinary differential equations (ODEs), using noisy and sparse data, is a vital task in many fields. We propose a fast and accurate method, manifold-constrained Gaussian process inference (MAGI), for this task. MAGI uses a Gaussian process model over time series data, explicitly conditioned on the manifold constraint that derivatives of the Gaussian process must satisfy the ODE system. By doing so, we completely bypass the need for numerical integration and achieve substantial savings in computational time. MAGI is also suitable for inference with unobserved system components, which often occur in real experiments. MAGI is distinct from existing approaches as we provide a principled statistical construction under a Bayesian framework, which incorporates the ODE system through the manifold constraint. We demonstrate the accuracy and speed of MAGI using realistic examples based on physical experiments.
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http://dx.doi.org/10.1073/pnas.2020397118DOI Listing
April 2021

Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents.

Sci Adv 2021 Apr 9;7(15). Epub 2021 Apr 9.

National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD ( = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet ( = 14). Over a 3-week treatment, KD compared to SA showed lower "wanting" and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.
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http://dx.doi.org/10.1126/sciadv.abf6780DOI Listing
April 2021

Corrigendum to "Decreased expression of DEAD-Box Helicase 5 inhibits esophageal squamous cell carcinomas by regulating endoplasmic reticulum stress and autophagy".

Biochem Biophys Res Commun 2021 Apr 6. Epub 2021 Apr 6.

Department of Digestive Disease and Gastrointestinal Motility Research Room, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbrc.2021.03.050DOI Listing
April 2021

Diverse evolutionary origins of microbial [4 + 2]-cyclases in natural product biosynthesis.

Int J Biol Macromol 2021 Apr 6. Epub 2021 Apr 6.

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

Natural [4 + 2]-cyclases catalyze concerted cycloaddition during biosynthesis of over 400 natural products reported. Microbial [4 + 2]-cyclases are structurally diverse with a broad range of substrates. Thus far, about 52 putative microbial [4 + 2]-cyclases of 13 different types have been characterized, with over 20 crystal structures. However, how these cyclases have evolved during natural product biosynthesis remains elusive. Structural and phylogenetic analyses suggest that these different types of [4 + 2]-cyclases might have diverse evolutionary origins, such as reductases, dehydratases, methyltransferases, oxidases, etc. Divergent evolution of enzyme function might have occurred in these different families. Understanding the independent evolutionary history of these cyclases would provide new insights into their catalysis mechanisms and the biocatalyst design.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.010DOI Listing
April 2021