Publications by authors named "Lei Li"

4,543 Publications

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An Egg-Derived Sulfated -Acetyllactosamine Glycan Is an Antigenic Decoy of Influenza Virus Vaccines.

mBio 2021 Jun 15:e0083821. Epub 2021 Jun 15.

Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.

Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess different glycosylation patterns than viruses circulating among humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived glycan that is an antigenic decoy, with egg-binding MAbs reacting with a sulfated -acetyllactosamine (LacNAc). Half of subjects that received an egg-grown vaccine mounted an antibody response against this egg-derived antigen. Egg-binding monoclonal antibodies specifically bind viruses grown in eggs, but not viruses grown in other chicken-derived cells, suggesting that only egg-grown vaccines can induce antiegg antibodies. Notably, antibodies against the egg antigen utilized a restricted antibody repertoire and possessed features of natural antibodies, as most antibodies were IgM and had a simple heavy-chain complementarity-determining region 3. By analyzing a public data set of influenza virus vaccine-induced plasmablasts, we discovered egg-binding public clonotypes that were shared across studies. Together, this study shows that egg-grown vaccines can induce antibodies against an egg-associated glycan, which may divert the host immune response away from protective epitopes.
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http://dx.doi.org/10.1128/mBio.00838-21DOI Listing
June 2021

Initial PCR Testing Negative, but Chest CT Suggesting for Viral Pneumonia Urges for Repeated Testing for COVID-19 Diagnosis.

Front Mol Biosci 2021 26;8:640788. Epub 2021 May 26.

The Department of Respiratory Diseases and Critic Care Unit, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

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http://dx.doi.org/10.3389/fmolb.2021.640788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189476PMC
May 2021

The Central Roles of Noncoding RNA in Estrogen-Dependent Female Reproductive System Tumors.

Int J Endocrinol 2021 24;2021:5572063. Epub 2021 May 24.

Department of Gynecology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.

The pathogenesis of ovarian and endometrial cancers is closely associated with estrogen-related pathways. These estrogen-dependent tumors seriously threaten the health and quality of life in women. Noncoding RNAs (ncRNAs) are defined as RNAs that do not encode proteins, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which have been reported in estrogen-dependent female reproductive system tumors. This review systematically summarizes the role of ncRNAs in estrogen-dependent tumors and common patterns of regulatory mechanisms to explore their future research directions in tumor diagnosis, treatment, and prognosis. This may provide new ideas for the potential application of ncRNAs in estrogen-dependent female reproductive system tumors.
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http://dx.doi.org/10.1155/2021/5572063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169271PMC
May 2021

Current and Future Roles of Circular RNAs in Normal and Pathological Endometrium.

Front Endocrinol (Lausanne) 2021 26;12:668073. Epub 2021 May 26.

Department of Gynecology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.

The uterine endometrium, which lines the mammalian uterus, is essential for embryo implantation. This lining undergoes significant changes during sexual and menstrual cycles. The endometrium is also associated with hormone-related diseases such as endometriosis and endometrial cancer. Circular RNAs (circRNAs) play a role in various biological processes. Recent studies have determined that circRNAs function in both normal and pathological endometrial environments. Here, we review high-throughput studies pertaining to circRNAs as well as individual circRNAs active in the endometrium, in order to explore the myriad functions of circRNAs in the endometrium and mechanisms underlying these functions, from panoramic and individual perspectives. Owing to their abundant expression, stability, and small size, circRNAs have displayed potential usefulness as diagnostic markers and treatment targets for endometrial-related diseases. Therefore, the specific role of circRNAs in the endometrium warrants systematic investigation in the future.
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http://dx.doi.org/10.3389/fendo.2021.668073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187767PMC
May 2021

Increasing Gap Between Thyroid Cancer Incidence and Mortality in Urban Shanghai, China: An Analysis Spanning 43 Years.

Endocr Pract 2021 Jun 10. Epub 2021 Jun 10.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China; Shanghai Clinical Research Promotion and Development Center, Shanghai Hospital Development Center, Shanghai 200041, People's Republic of China. Electronic address:

Objective: We aimed to examine secular trends of thyroid cancer incidence and mortality and to estimate the proportion of thyroid cancer cases potentially attributable to overdiagnosis.

Methods: Data on thyroid cancer cases from 1973 to 2015 were obtained from Shanghai Cancer Registry. Average annual percent changes (AAPCs) were evaluated by Joinpoint regression analysis. Age, period, and birth cohort effects were assessed by age-period-cohort model. Overdiagnosis of thyroid cancer cases was estimated from the difference between observed and expected incidences using the rates of the Nordic countries as reference.

Results: From 1973 to 2015, the number of thyroid cancer cases was 23,117, and 75% were female. Age-standardized rates were seven to eight-fold higher in 2013-2015 than in 1973-1977. Compared with relatively stable mortality, thyroid cancer incidence was dramatically increased from 2002 to 2015 in both genders with significant trends (men: AAPC =21.84%, 95%CI: 18.77%-24.98%, P<0.001; women: AAPC=18.55%, 95%CI: 16.49%-20.64%, P<0.001). The proportion of overdiagnosis has been gradually increased over time, rising from 68% in 2003-2007 to more than 90% in 2013-2015, and the increasing pattern appeared to be similar between men and women.

Conclusion: An increasing gap between thyroid cancer incidence and mortality was observed in Shanghai and overdiagnosis has contributed substantially on the rise of incidence, which calls for an urgent update on the practice of thyroid examination.
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http://dx.doi.org/10.1016/j.eprac.2021.06.002DOI Listing
June 2021

Synergy between pyridine anaerobic mineralization and vanadium (V) oxyanion bio-reduction for aquifer remediation.

J Hazard Mater 2021 Jun 5;418:126339. Epub 2021 Jun 5.

National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Guangdong Institute of Eco-environmental Science & Technology, Guangdong Academy of Sciences, Guangzhou 510650, PR China.

The co-occurrence of toxic pyridine (Pyr) and vanadium (V) oxyanion [V(V)] in aquifer has been of emerging concern. However, interactions between their biogeochemical fates remain poorly characterized, with absence of efficient route to decontamination of this combined pollution. In this work, microbial-driven Pyr degradation coupled to V(V) reduction was demonstrated for the first time. Removal efficiencies of Pyr and V(V) reached 94.8 ± 1.55% and 51.2 ± 0.20% in 72 h operation. The supplementation of co-substrate (glucose) deteriorated Pyr degradation slightly, but significantly promoted V(V) reduction efficiency to 84.5 ± 0.635%. Pyr was mineralized with NH-N accumulation, while insoluble vanadium (IV) was the major product from V(V) bio-reduction. It was observed that Bacillus and Pseudomonas realized synchronous Pyr and V(V) removals independently. Interspecific synergy between Pyr degraders and V(V) reducers also functioned with addition of co-substrate. V(V) was bio-reduced through alternative electron acceptor pathway conducted by gene nirS encoded nitrite reductase, which was evidenced by gene abundance and enzyme activity. Cytochrome c, nicotinamide adenine dinucleotide and extracellular polymeric substances also contributed to the coupled bioprocess. This work provides new insights into biogeochemical activities of Pyr and V(V), and proposes novel strategy for remediation of their co-contaminated aquifer.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126339DOI Listing
June 2021

Safety and efficiency of modified sacrospinous ligament fixation for apical prolapse: Long-term studies and outcomes.

Int J Gynaecol Obstet 2021 Jun 12. Epub 2021 Jun 12.

Department of gynecological pelvic floor and oncology, Chongqing health center for women and children, Chongqing, China.

Objective: To explore the safety and efficiency of modified sacrospinous ligament fixation (MSSF) for apical prolapse.

Methods: It's a retrospective cohort study. Patients diagnosed with apical prolapse from 2014 to 2019 were recruited and divided into three groups, those are sacrospinous ligament fixation (SSF), MSSF and laparoscopic sacral hysteropexy (LSH). All surgical characteristics were obtained and information concerning complications was collected and compared among these three groups.

Results: A total of 710 patients were collected eventually, including 108 in SSF group, 260 in LSH and 342 in MSSF. MSSF and SSF group cost less surgical time(P<0.001) and hospital stay(P<0.001). All these three methods can significant change the prolapse with point C(P<0.001). Prevalence of Vaginal and pelvic pain after surgery were higher in group SSF (8/108 (7.41%)) (P=0.028), urinary incontinence seemed much higher in group LSH (22/260 (8.46%)) (P=0.010). In group LSH, there were more patients suffered from constipation and dyschezia after surgery, the prevalence were 18/260 (6.92%) (P=0.048). Recurrence of POP in group MSSF (15/324 (4.39%)) and group LSH (12/260 (4.62%)) were much lower than SSF group (16/108 (14.81%)) (P<0.001).

Conclusion: the efficacy of MSSF is commendable with low recurrence of POP and few complications in long-term follow-up.
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http://dx.doi.org/10.1002/ijgo.13786DOI Listing
June 2021

Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.

Nat Commun 2021 06 11;12(1):3573. Epub 2021 Jun 11.

Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.

O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression. Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds. Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans. The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules. A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray. Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics. Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
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http://dx.doi.org/10.1038/s41467-021-23428-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196059PMC
June 2021

Mammary Lobular Carcinoma-Like Salivary Gland Carcinoma: Report of a Rare Case.

Head Neck Pathol 2021 Jun 11. Epub 2021 Jun 11.

Department of Pathology, Stanford University Medical Center, Palo Alto, USA.

Salivary and mammary glands are both exocrine organs sharing multiple tumorigenic processes. To the best of our knowledge, salivary gland tumors mimicking invasive lobular carcinoma of the breast have not yet been described. Herein, we report a case of a 62-year-old male who presented with progressive facial paralysis. Pathologic examination revealed an ill-defined epithelial neoplasm exhibiting discohesive growth set within an extensively fibrotic stroma. Both perineural and intraneural invasion were present. E-cadherin and p120 immunostaining showed aberrant cytoplasmic expression. Targeted next-generation sequencing detected a frameshift mutation of the CTNNA1 gene as the only known pathogenic variant. The patient was treated with surgical resection, immunotherapy, and chemotherapy. Currently, he is alive with disease twenty months after disease onset.
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http://dx.doi.org/10.1007/s12105-021-01344-2DOI Listing
June 2021

Fighting against fast speckle decorrelation for light focusing inside live tissue by photon frequency shifting.

ACS Photonics 2020 Mar 26;7(3):837-844. Epub 2020 Feb 26.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Focusing light inside live tissue by digital optical phase conjugation (DOPC) has been intensively investigated due to its potential biomedical applications in deep-tissue imaging, optogenetics, microsurgery, and phototherapy. However, fast physiological motions in a live animal, such as blood flow and respiratory motions, produce undesired photon perturbation and thus inevitably deteriorate the performance of light focusing. Here, we develop a photon-frequency-shifting DOPC method to fight against fast physiological motions by switching the states of a guide star at a distinctive frequency. Therefore, the photons tagged by the guide star are well detected at the specific frequency, separating them from the photons perturbed by fast motions. Light focusing was demonstrated in both phantoms in vitro and mice in vivo with substantially improved focusing contrast. This work puts a new perspective on light focusing inside live tissue and promises wide biomedical applications.
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http://dx.doi.org/10.1021/acsphotonics.0c00027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188831PMC
March 2020

An ionic covalent organic framework for rapid extraction of polar organic acids from environmental waters.

Anal Methods 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.

An ionic covalent organic framework ([email protected]) as a polar adsorbent was synthesized and characterized. It was applied in the magnetic solid phase extraction (MSPE) of four polar organic acids, namely, 2-(2,4,5-trichlorophenoxy)propionic acid, 2-methyl-4-chlorophenoxy acetic acid, naphthyloxyacetic acid, and naphthylacetic acid. The organic acids were detected by high performance liquid chromatography-ultraviolet analysis (HPLC-UV). A method for the determination of organic acids based on MSPE-HPLC-UV was established. The method shows good linear regression (R2 ≥ 0.9950), high precision (1.53-3.80%, n = 6), and low detection limit (0.10-0.49 ng mL-1). The recovery rate of environmental water samples ranges from 73.3% to 101.0%. This method provides a possibility for high sensitivity analysis of polar organic acids.
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http://dx.doi.org/10.1039/d1ay00679gDOI Listing
June 2021

Scheduling fixed length quarantines to minimize the total number of fatalities during an epidemic.

J Math Biol 2021 Jun 8;82(7):69. Epub 2021 Jun 8.

School of Mathematical Sciences, Institute of Natural Sciences, MOE-LSC, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

We consider a susceptible, infected, removed (SIR) system where the transmission rate may be temporarily reduced for a fixed amount of time. We show that in order to minimize the total number of fatalities, the transmission rate should be reduced on a single contiguous time interval, and we characterize this interval via an integral condition. We conclude with a few numerical simulations showing the actual reduction obtained.
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http://dx.doi.org/10.1007/s00285-021-01615-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185504PMC
June 2021

Tunable Dual-Effector Allostery System for Nucleic Acid Analysis with Enhanced Sensitivity and an Extended Dynamic Range.

Anal Chem 2021 Jun 6;93(23):8170-8177. Epub 2021 Jun 6.

Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, P. R. China.

In the last few years, studies have demonstrated the existence of dual-effector allosteric cooperativity in nature and the mechanism underlying enhanced activation/inhibition performance. In this work, we design an artificial dual-effector allostery system for the construction of a dynamic biosensor that can achieve nucleic acid detection with superior sensitivity and across an extraordinary broad detection range. Our dual-effector allostery-regulated biosensor is based on the multibranched hybridization chain reaction (mHCR) involving three hairpins (H1, H2, and H3). In the presence of the target nucleic acid, the mHCR is initiated via cascading strand displacement events. The products of mHCR are then captured on the electrode surface based on the mechanism of the multivalent proximity ligation assay (mPLA) and the multivalent binding assay (mBA). The subsequent conjugation of streptavidin-modified horseradish peroxidase (SA-HRP) can lead to an increase in the electrochemical signal. Importantly, two distinct allosteric activation sites and two distinct allosteric inhibition sites in H1 are designed to fine-tune the nucleic acid detection sensitivity and the dynamic range. Using this new dual-effector allostery tool, we report the detection of nucleic acid at a dynamic range spanning 10-10 aM, 11 orders of magnitude showing the broadest dynamic range reported to date with an allosteric regulation biosensor construct.
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http://dx.doi.org/10.1021/acs.analchem.1c00055DOI Listing
June 2021

HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4.

Front Oncol 2021 21;11:645979. Epub 2021 May 21.

Department of Breast Surgical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China.

Purpose: Chemoresistance remains a major challenge in the therapy of gastric cancer (GC). The homeobox (HOX) gene family has gained attention in carcinogenesis and chemoresistance. Here, this study aimed to explore the mechanism of HOXA13 in GC chemoresistance.

Methods: Quantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate the expression of HOXA13 in GC tissues. The Kaplan-Meier plotter database was mined for prognosis analysis of GC patients with different HOXA13 expression receiving 5-Fluorouracil (5-FU) therapy. The effects of HOXA13 on sensitivity of GC cells to 5-FU were investigated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) incorporation, flow cytometry and experiment . RNA-Sequencing analysis was performed to explore the underlying mechanism of HOXA13-mediated 5-FU resistance in GC. Chromatin immunoprecipitation (ChIP) and rescue experiments were applied to determine the relationship between HOXA13 and ABCC4. Luciferase reporter assay was performed to assess interaction of miR-139-5p and HOXA13.

Results: HOXA13 was upregulated in GC and its high expression was associated with poor prognosis of GC patients with 5-FU treatment. Overexpression of HOXA13 impaired the inhibitory effects of 5-FU on GC cells proliferation and , and knockdown of HOXA13 exacerbated 5-FU-induced GC cells apoptosis. Mechanistically, HOXA13, directly targeted by miR-139-5p in GC, might upregulate ABCC4 expression, thereby accentuating 5-FU resistance of GC cells.

Conclusion: Our study suggests that HOXA13 attenuates 5-FU sensitivity of GC possibly by upregulating ABCC4. Thus, targeting HOXA13 would provide a novel prospective into the potential therapeutic strategy for reversing chemoresistance.
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http://dx.doi.org/10.3389/fonc.2021.645979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175971PMC
May 2021

Dynamic, multimodal hydrogel actuators using porphyrin-based visible light photoredox catalysis in a thermoresponsive polymer network.

Chem Sci 2020 Sep 3;11(40):10910-10920. Epub 2020 Sep 3.

Department of Chemistry, Washington University One Brookings Drive St. Louis MO 63130 USA

Hydrogels that can respond to multiple external stimuli represent the next generation of advanced functional biomaterials. Here, a series of multimodal hydrogels were synthesized that can contract and expand reversibly over several cycles while changing their mechanical properties in response to blue and red light, as well as heat (∼50 °C). The light-responsive behavior was achieved through a photoredox-based mechanism consisting of photoinduced electron transfer from a zinc porphyrin photocatalyst in its excited state to oligoviologen-based macrocrosslinkers, both of which were integrated into the hydrogel polymer network during gel formation. Orthogonal thermoresponsive properties were also realized by introducing -isopropyl acrylamide (NIPAM) monomer simultaneously with hydroxyethyl acrylate (HEA) in the pre-gel mixture to produce a statistical 60 : 40 HEA : NIPAM polymer network. The resultant hydrogel actuators - crosslinked with either a styrenated viologen dimer () or hexamer () - were exposed to red or blue light, or heat, for up to 5 h, and their rate of contraction, as well as the corresponding changes in their physical properties (, stiffness, tensile strength, Young's modulus, ), were measured. The combined application of blue light and heat to the -based hydrogels was also demonstrated, resulting in hydrogels with more than two-fold faster contraction kinetics and dramatically enhanced mechanical robustness when fully contracted. We envision that the reported materials and the corresponding methods of remotely manipulating the dynamic hydrogels may serve as a useful blueprint for future adaptive materials used in biomedical applications.
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http://dx.doi.org/10.1039/d0sc04287kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162415PMC
September 2020

Photoisomerization of dicyanorhodanine-functionalized thiophenes.

Chem Sci 2020 Sep 9;11(37):10190-10197. Epub 2020 Sep 9.

Department of Chemistry, University of Florida PO Box 117200 Gainesville FL 32611 USA

π-Conjugated oligomers functionalized with the popular dicyanorhodanine (RCN) electron acceptor are shown to be susceptible to photo-induced / isomerization. The stereochemistry of two model RCN-functionalized thiophenes is confirmed by single crystal X-ray analysis and 2D NMR, and shown to be the thermodynamically stable form. Relative energies, / configurations, and conformational preferences are modelled using density functional theory (DFT). The photophysical properties of the model compounds are explored experimentally and computationally; the and isomers display similar absorption profiles with significant spectral overlap and are inseparable upon irradiation to a photostationary state. The well-behaved photoisomerization process is routinely observable by thin-layer chromatography, UV-vis, and NMR, and the photochemical behavior of the two RCN-functionalized thiophenes is characterized under varying wavelengths of irradiation. Ultraviolet (254 nm) irradiation results in photostationary state compositions of 56/44 and 69/31 -isomer/-isomer for substrates functionalized with one thiophene and two thiophenes, respectively. Ambient laboratory lighting results in excess of 10 percent -isomer for each species in solution, an important consideration for processing such materials, particularly for organic photovoltaic applications. In addition, a photoswitching experiment is conducted to demonstrate the reversible nature of the photoreaction, where little evidence of fatigue is observed over numerous switching cycles. Overall, this work showcases an approach to characterize the stereochemistry and photochemical behavior of dicyanorhodanine-functionalized thiophenes, widely used components of functional molecules and materials.
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http://dx.doi.org/10.1039/d0sc04409aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162279PMC
September 2020

Therapeutic Potential of TNFα and IL1β Blockade for CRS/ICANS in CAR-T Therapy Ameliorating Endothelial Activation.

Front Immunol 2021 19;12:623610. Epub 2021 May 19.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) strongly hampered the broad clinical applicability of chimeric antigen receptor T cell (CAR-T) therapy. Vascular endothelial activation has been suggested to contribute to the development of CRS and ICANS after CAR-T therapy. However, therapeutic strategies targeting endothelial dysfunction during CAR-T therapy have not been well studied yet. Here, we found that tumor necrosis factor α (TNFα) produced by CAR-T cells upon tumor recognition and interleukin 1β (IL1β) secreted by activated myeloid cells were the main cytokines in inducing endothelial activation. Therefore, we investigated the potential effectiveness of TNFα and IL1β signaling blockade on endothelial activation in CAR-T therapy. The blockade of TNFα and IL1β with adalimumab and anti-IL1β antibody respectively, as well as the application of focal adhesion kinase (FAK) inhibitor, effectively ameliorated endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Moreover, adalimumab and anti-IL1β antibody exerted synergistic effect on the prevention of endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Our results indicate that TNFα and IL1β blockade might have therapeutic potential for the treatment of CAR-T therapy-associated CRS and neurotoxicity.
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http://dx.doi.org/10.3389/fimmu.2021.623610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170323PMC
May 2021

The bioinformatics and metabolomics research on anti-hypoxic molecular mechanisms of Salidroside via regulating the PTEN mediated PI3K/Akt/NF-κB signaling pathway.

Chin J Nat Med 2021 Jun;19(6):442-453

Department of Pharmacology, Beijing Laboratory for Biomedical Detection Technology and Instrument, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Beijing Engineering Research Center for Nerve System Drugs, Beijing 100053, China. Electronic address:

Salidroside (SAL), a major bioactive compound of Rhodiola crenulata, has significant anti-hypoxia effect, however, its underlying molecular mechanism has not been elucidated. In order to explore the protective mechanism of SAL, the lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD) and hypoxia-induced factor 1α (HIF-1α) were measured to establish the PC12 cell hypoxic model. Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL. The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition. The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting. The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2, p-PTEN/PTEN, PI3K, p-Akt/Akt, NF-κB p65 and Bcl-2 were increased, suggesting that SAL could increase the expression of CK2, which induced the phosphorylation and inactivation of PTEN, reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway. Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.
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http://dx.doi.org/10.1016/S1875-5364(21)60043-2DOI Listing
June 2021

Social Comparison Orientation and Cyberbullying Perpetration and Victimization: Roles of Envy on Social Networking Sites and Body Satisfaction.

J Interpers Violence 2021 Jun 6:8862605211023486. Epub 2021 Jun 6.

Renmin University of China, Haidian District, Beijing, China.

Although some studies have explored the psychological and behavioral outcomes of social comparison orientation (SCO), few have explored the associations of SCO with cyberbullying perpetration and victimization. The current study aimed to investigate the associations of SCO with cyberbullying perpetration and victimization, and considered envy on social networking sites (SNS) as a mediator and body satisfaction as a moderator in these relations. To test our expectations, 941 adolescents aged between 10 and 16 years ( = 13.15, SD = 1.18) completed multiple questionnaires, namely the Social Comparison Orientation Scale, the Revised Cyber Bullying Inventory, an envy scale revised for the SNS context, and the Body Areas Satisfaction Scale. Correlation analysis revealed that cyberbullying perpetration and cyberbullying victimization were significantly and positively correlated with SCO and envy on SNS, and significantly and negatively correlated with body satisfaction. The results of structural equation modeling (SEM) revealed that envy on SNS played a mediating role in the associations of SCO with cyberbullying perpetration and victimization. The results of SEM and simple slope test analysis indicated that body satisfaction weakened the direct association of SCO with envy on SNS and further weakened the indirect associations of SCO with cyberbullying perpetration and victimization via envy on SNS. Specifically, individuals with high levels of SCO were more likely to feel envious on SNS, and further tended to bully others and be bullied online when they were dissatisfied with their bodies. In other words, positive body satisfaction protected individuals with high levels of SCO from cyberbullying perpetration and victimization by decreasing their feelings of envy on SNS.
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http://dx.doi.org/10.1177/08862605211023486DOI Listing
June 2021

A modified transalveolar sinus floor elevation approach with a bilaterally enlarged osteotomy.

J Oral Implantol 2021 Jun 6. Epub 2021 Jun 6.

West China School of Stomatology, Sichuan University State Key Laboratory of OA No.14, Section 3, South Peoples Road CHINA Chengdu 44 610041 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China School of Stomatology, Sichuan University.

Sinus floor elevation is the most commonly used method for vertical bone augmentation in the maxillary posterior area. This clinical report describes a modified transalveolar approach to elevate the sinus floor when placing implants on a severely resorbed maxillary posterior ridge with a buccal-palatal distance of more than 8.0 mm. In this approach, the osteotomy prepared on the crestal is bilaterally enlarged to 8.0-10.0 mm. The enlarged osteotomies can provide better access for practitioners, so that instruments can touch directly to the sinus floor and the Schneiderian membrane can be elevated with a reduced risk of perforation.
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http://dx.doi.org/10.1563/aaid-joi-D-20-00173DOI Listing
June 2021

The influence of perceived parental phubbing on adolescents' problematic smartphone use: A two-wave multiple mediation model.

Addict Behav 2021 Oct 31;121:106995. Epub 2021 May 31.

School of Education, Renmin University of China, No. 59 Zhongguancun Street, Haidian District, Beijing 100872, China. Electronic address:

Using a two-wave longitudinal design, the current study examined the relationship between early perceived parental phubbing and subsequent problematic smartphone use. As loneliness is a sensitive indicator of interpersonal problems and fear of missing out is a strong predictor of Internet-related addiction, we examined these two variables as possible mediators in this relationship based on existing literature. A total of 1447 Chinese adolescents (572 males and 875 females, mean age = 16.15 years) completed questionnaires regarding perceived parental phubbing, loneliness, fear of missing out, and problematic smartphone use. The results indicated that: (a) early fathers' phubbing (fphubbing) and mothers' phubbing (mphubbing) predicted adolescents' subsequent problematic smartphone use; (b) loneliness mediated the relationship between early fphubbing/mphubbing and adolescents' subsequent problematic smartphone use; and (c) loneliness and fear of missing out sequentially mediated the relationship between early fphubbing/mphubbing and adolescents' subsequent problematic smartphone use. These results suggested that three types of interventions could be effectively used to decrease the risk of problematic smartphone use among adolescents, namely, reducing perceived parental phubbing, relieving loneliness, and decreasing fear of missing out.
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http://dx.doi.org/10.1016/j.addbeh.2021.106995DOI Listing
October 2021

Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-β and reactive oxygen species.

Chem Sci 2021 Apr 13;12(18):6449-6457. Epub 2021 Apr 13.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University Shanghai 200062 China

The excessive production and deposition of amyloid-β (Aβ) is one of the most important etiologies of Alzheimer's disease (AD). The interaction between Aβ and metal ions produces aberrant reactive oxygen species (ROS), which induce oxidative stress and accelerate the progression of AD. To reduce Aβ plaques and ROS to maintain their homeostasis is an emerging and ingenious strategy for effective treatment of AD. Herein, we report the rational design of multifunctional micelles (MPGLT) based on a polymer-grafted peptide to simultaneously clear Aβ and ROS for AD therapy. The MPGLT integrating three functional peptides as a ROS scavenger (tk-GSH), β-sheet breaker (LP) and an autophagy activator (TK) respectively, could capture and degrade Aβ. Meanwhile, the tk-GSH on the surface of MPGLT effectively scavenges the intracellular ROS. Consequently, MPGLT reduced the cytotoxicity of Aβ and ROS. animal studies using an AD mouse model further showed that MPGLT could transport across the blood-brain barrier for decreasing the Aβ plaque and eliminating ROS . This peptide micelle-based synergistic strategy may provide novel insight for AD therapy.
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http://dx.doi.org/10.1039/d1sc00153aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115327PMC
April 2021

PDGF-BB regulates the transformation of fibroblasts into cancer-associated fibroblasts via the lncRNA LURAP1L-AS1/LURAP1L/IKK/IκB/NF-κB signaling pathway.

Oncol Lett 2021 Jul 19;22(1):537. Epub 2021 May 19.

Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

The most abundant cells in the tumor microenvironment are cancer-associated fibroblasts (CAFs). They play an important role in oral squamous cell carcinoma (OSCC) angiogenesis, invasion and metastasis. Platelet-derived growth factor (PDGF)-BB has an obvious regulating effect on the formation of CAFs through binding to PDGF receptor (PDGFR)-β, but the role of long non-coding (lnc)RNA in PDGF-BB-induced transformation of fibroblasts into CAFs remains poorly understood. Using an lncRNA ChIP, 370 lncRNA transcripts were identified to be significantly and differentially expressed between fibroblasts and PDGF-BB-induced fibroblasts, including 240 upregulated lncRNAs and 130 downregulated lncRNAs, indicating that lncRNAs are involved in the regulation of the transformation of CAFs. Previous studies have shown that the nuclear factor (NF)-κB signaling pathway plays an important role in the activation of CAFs. Dual-luciferase reporter assay and co-immunoprecipitation were conducted to confirm that the leucine-rich adaptor protein 1-like (LURAP1L), which is the target of lncRNA LURAP1L antisense RNA 1 (LURAP1L-AS1) had a positive regulatory effect on I-κB kinase (IKK)/NF-κB signaling. Therefore, LURAP1L-AS1 was selected and PDGF-BB was demonstrated to upregulate the expression of LURAP1L-AS1 and LURAP1L, which was reversed by a PDGFR-β inhibitor. Subsequently, knocking down LURAP1L-AS1 suppressed the expression of PDGF-BB-induced fibroblast activation marker protein α-smooth muscle actin, fibroblast activation protein-α, PDGFR-β and phosphorylated (p)-PDGFR-β. IKKα, p-IĸB and p-NF-κB were downregulated by the knockdown of LURAP1L-AS1 and upregulated by overexpression of LURAP1L-AS1. The present study indicates that LURAP1L-AS1/LURAP1L/IKK/IĸB/NF-κB plays an important regulatory role in PDGF-BB-induced fibroblast activation and may become a potential target for the treatment of OSCC.
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http://dx.doi.org/10.3892/ol.2021.12798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157341PMC
July 2021

First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes.

Sci Transl Med 2021 Jun;13(596)

Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA.

Broadly neutralizing antibodies are critical for protection against both drifted and shifted influenza viruses. Here, we reveal that first exposure to the 2009 pandemic H1N1 influenza virus recalls memory B cells that are specific to the conserved receptor-binding site (RBS) or lateral patch epitopes of the hemagglutinin (HA) head domain. Monoclonal antibodies (mAbs) generated against these epitopes are broadly neutralizing against H1N1 viruses spanning 40 years of viral evolution and provide potent protection in vivo. Lateral patch-targeting antibodies demonstrated near universal binding to H1 viruses, and RBS-binding antibodies commonly cross-reacted with H3N2 viruses and influenza B viruses. Lateral patch-targeting mAbs were restricted to expressing the variable heavy-chain gene VH3-23 with or without the variable kappa-chain gene VK1-33 and often had a Y-x-R motif within the heavy-chain complementarity determining region 3 to make key contacts with HA. Moreover, lateral patch antibodies that used both VH3-23 and VK1-33 maintained neutralizing capability with recent pH1N1 strains that acquired mutations near the lateral patch. RBS-binding mAbs used a diverse repertoire but targeted the RBS epitope similarly and made extensive contacts with the major antigenic site Sb. Together, our data indicate that RBS- and lateral patch-targeting clones are abundant within the human memory B cell pool, and universal vaccine strategies should aim to drive antibodies against both conserved head and stalk epitopes.
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http://dx.doi.org/10.1126/scitranslmed.abg4535DOI Listing
June 2021

Surgical laser positioning system assists removal of a cervical migratory foreign object.

Braz J Otorhinolaryngol 2021 Apr 27. Epub 2021 Apr 27.

Second Military Medical University (Naval Medical University), Changhai Hospital, Department of Orthopedics, Shanghai, China; Second Military Medical University (Naval Medical University), Changhai Hospital, Department of Emergency, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.bjorl.2021.03.013DOI Listing
April 2021

Fabrication of All-GaN Integrated MIS-HEMTs with High Threshold Voltage Stability Using Supercritical Technology.

Micromachines (Basel) 2021 May 18;12(5). Epub 2021 May 18.

School of Electronic and Computer Engineering, Peking University Shenzhen Graduate School, University Town, Xili, Nanshan, Shenzhen 518055, China.

In this paper, a novel method to achieve all-GaN integrated MIS-HEMTs in a Si-CMOS platform by self-terminated and self-alignment process is reported. Furthermore, a process of repairing interface defects by supercritical technology is proposed to suppress the threshold voltage shift of all GaN integrated MIS-HEMTs. The threshold voltage characteristics of all-GaN integrated MIS-HEMTs are simulated and analyzed. We found that supercritical NH3 fluid has the characteristics of both liquid NH3 and gaseous NH3 simultaneously, i.e., high penetration and high solubility, which penetrate the packaging of MIS-HEMTs. In addition, NH2- produced via the auto coupling ionization of NH3 has strong nucleophilic ability, and is able to fill nitrogen vacancies near the GaN surface created by high temperature process. The fabricated device delivers a threshold voltage of 2.67 V. After supercritical fluid treatment, the threshold voltage shift is reduced from 0.67 V to 0.13 V. Our demonstration of the supercritical technology to repair defects of wide-bandgap family of semiconductors may bring about great changes in the field of device fabrication.
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http://dx.doi.org/10.3390/mi12050572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157587PMC
May 2021

Two Different Inoculation Methods Unveiled the Relative Independence of DON Accumulation in Wheat Kernels from Disease Severity on Spike after Infection by Fusarium Head Blight.

Toxins (Basel) 2021 05 14;13(5). Epub 2021 May 14.

Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Key Laboratory of Plant Functional Genomics of the Ministry of Education/Collaborative-Innovation of Modern Crops and Food Crops in Jiangsu/Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China.

Fusarium head blight (FHB) causes wheat yield loss and mycotoxin (deoxynivalenol, DON) accumulation in wheat kernel. Developing wheat cultivars with overall resistance to both FHB spread within a spike and DON accumulation in kernels is crucial for ensuring food security and food safety. Here, two relatively novel inoculation methods, bilateral floret inoculation (BFI) and basal rachis internode injection (BRII), were simultaneously employed to evaluate disease severity and DON content in kernels in a segregating population of recombinant inbred lines (RILs) developed from Ning 7840 (carrying ) and Clark (without ). Under both inoculation methods, four contrasting combinations of disease severity and DON content were identified: high severity/high DON (HSHD), high severity/low DON (HSLD), low severity/high DON (LSHD) and low severity/low DON (LSLD). Unexpectedly, the BRII method clearly indicated that disease severity was not necessarily relevant to DON concentration. The effects of on disease severity, and on DON concentrations, agreed very well across the two methods. Several lines carrying showed extremely higher severity and (or) DON content under both inoculation methods. The "Mahalanobis distance" (MD) method was used to rate overall resistance of a line by inclusion of both disease severity and DON content over both methods to select LSLD lines.
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http://dx.doi.org/10.3390/toxins13050353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156083PMC
May 2021

A Heterozygous Genotype-Dependent Branched-Spike Wheat and the Potential Genetic Mechanism Revealed by Transcriptome Sequencing.

Biology (Basel) 2021 May 14;10(5). Epub 2021 May 14.

Key Laboratory of Plant Functional Genomics of the Ministry of Education, Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, Collaborative Innovation of Modern Crops and Food Crops in Jiangsu, Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China.

Wheat ( L.) spike architecture is an important trait associated with spike development and grain yield. Here, we report a naturally occurring wheat mutant with branched spikelets (BSL) from its wild-type YD-16, which has a normal spike trait and confers a moderate level of resistance to wheat Fusarium head blight (FHB). The lateral meristems positioned at the basal parts of the rachis node of the BSL mutant develop into ramified spikelets characterized as multiple spikelets. The BSL mutant shows three to four-day longer growth period but less 1000-grain weight than the wild type, and it becomes highly susceptible to FHB infection, indicating that the locus controlling the BSL trait may have undergone an intensively artificial and/or natural selection in modern breeding process. The self-pollinated descendants of the lines with the BSL trait consistently segregated with an equal ratio of branched and normal spikelets (NSL) wheat, and homozygotes with the BSL trait could not be achieved even after nine cycles of self-pollination. Distinct segregation patterns both from the self-pollinated progenies of the BSL plants and from the reciprocal crosses between the BSL plants with their sister NSL plants suggested that gametophytic male sterility was probably associated with the heterozygosity for the BSL trait. Transcriptome sequencing of the RNA bulks contrasting in the two types of spike trait at the heading stage indicated that the genes on chromosome 2D may be critical for the BSL trait formation since 329 out of 2540 differentially expressed genes (DEGs) were located on that chromosome, and most of them were down-regulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that carbohydrate metabolism may be involved in the BSL trait expression. This work provides valuable clues into understanding development and domestication of wheat spike as well as the association of the BSL trait with FHB susceptibility.
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http://dx.doi.org/10.3390/biology10050437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157103PMC
May 2021

Case Report: F-PSMA PET/CT May Improve the Clinical Management of Penile Metastases From Prostate Cancer.

Front Oncol 2021 13;11:683343. Epub 2021 May 13.

Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Metastases from prostate cancer (PCa) to the penis are extremely rare, and few case reports exist in the literature. Because most patients usually present with multiple distant metastases at diagnosis, the prognosis is very poor. With the wide application of prostate-specific membrane antigen (PSMA) PET/CT, penile metastases may be detected at an early stage. Thus, questions regarding whether early diagnosis and precise treatment will equate to a survival advantage have recently been raised. In the present study, we reported 3 cases of penile metastasis from castration-resistant PCa. Moreover, a patient with asymptomatic penile metastases was diagnosed by F-PSMA PET/CT followed by lesion biopsy, and the prognosis was very well, despite with an aggressive pathological feature and low treatment intensity. In addition, we performed a literature review and found 62.5% of asymptomatic penile metastases were diagnosed by PSMA PET/CT in past seven years. Thus, we believe that PSMA PET/CT may detect more asymptomatic penile metastases in future, which led to early diagnosis, treatment and survival advantage.
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http://dx.doi.org/10.3389/fonc.2021.683343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155605PMC
May 2021

Systematic investigation on the anti-rheumatoid arthritis material basis and mechanism of Juan Bi Tang. Part 1: Integrating metabolic profiles and network pharmacology.

J Pharm Biomed Anal 2021 Aug 12;202:114133. Epub 2021 May 12.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China; College of Life and Environmental Sciences, Shanghai Normal University, Shanghai, 201203, China. Electronic address:

Previously, our cooperative team confirmed the chemical composition and anti-rheumatoid arthritis (RA) efficacy of Juanbi-Tang (JBT), a clinically and historically used traditional Chinese medicine formula, in two model animals. In this study, we developed an in vivo-in silico strategy to elucidate the anti-RA material basis and mechanism of JBT. With the aid of high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF), the metabolic profiles were investigated in normal and collagen-induced arthritis RA rats following oral administration of JBT. Based on the absorbed constituents in RA rats, network pharmacology was employed to predict the anti-RA mechanisms, followed by molecular docking validation. Consequently, there were 18 absorbed compounds with 6 chemical structures, which were absolutely identified by matching with standard compounds in plasma, and 17 generated metabolites involved of 7 biotransformation pathways, including glucuronidation, sulfation, hydroxylation, deglycosylation, methylation, taurine, and glycine conjugation. Moreover, RA disease affected the absorption and metabolism of the constituents in JBT, given the undetected 2 absorbed compounds and 4 metabolites in RA rats. The analysis of network pharmacology indicated that those absorbed compounds in JBT may fight against RA through the MAPK, FoxO, and Rap1 pathways. Molecular docking also validated these results. Overall, this is the first study to describe the metabolic profiles of JBT-treated healthy and RA rats, and it provides a possible anti-RA mechanism through multiple absorbed compounds and targets by network pharmacology.
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http://dx.doi.org/10.1016/j.jpba.2021.114133DOI Listing
August 2021