Publications by authors named "Tong Lin"

392 Publications

Detection of Mutual Exciting Structure in Stock Price Trend Dynamics.

Entropy (Basel) 2021 Oct 27;23(11). Epub 2021 Oct 27.

School of Computer Science and Engineering and NLSDE, Beihang University, Beijing 100191, China.

We investigated a comprehensive analysis of the mutual exciting mechanism for the dynamic of stock price trends. A multi-dimensional Hawkes-model-based approach was proposed to capture the mutual exciting activities, which take the form of point processes induced by dual moving average crossovers. We first performed statistical measurements for the crossover event sequence, introducing the distribution of the inter-event times of dual moving average crossovers and the correlations of local variation (LV), which is often used in spike train analysis. It was demonstrated that the crossover dynamics in most stock sectors are generally more regular than a standard Poisson process, and the correlation between variations is ubiquitous. In this sense, the proposed model allowed us to identify some asymmetric cross-excitations, and a mutually exciting structure of stock sectors could be characterized by mutual excitation correlations obtained from the kernel matrix of our model. Using simulations, we were able to substantiate that a burst of the dual moving average crossovers in one sector increases the intensity of burst both in the same sector (self-excitation) as well as in other sectors (cross-excitation), generating episodes of highly clustered burst across the market. Furthermore, based on our finding, an algorithmic pair trading strategy was developed and backtesting results on real market data showed that the mutual excitation mechanism might be profitable for stock trading.
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http://dx.doi.org/10.3390/e23111411DOI Listing
October 2021

Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis.

Front Genet 2021 29;12:764245. Epub 2021 Oct 29.

Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.

High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear. Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms. HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for in ACC; in ACC, LGG, LIHC, and SKCM; and in ESCA. Prognostic values were also found for in KIRP and MESO and in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events. This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.
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http://dx.doi.org/10.3389/fgene.2021.764245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585836PMC
October 2021

is a Promising Therapeutic Biomarker Associated with the Immune Microenvironment of Hepatocellular Carcinoma.

Int J Gen Med 2021 30;14:7487-7501. Epub 2021 Oct 30.

Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People's Republic of China.

Background: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is still poor, effective therapeutic targets are needed. ZW10 interacting kinetochore protein (Zwint) is an essential component of the mitotic spindle checkpoint and is upregulated in cancers. Disappointing, the role of in HCC has not been fully illuminated.

Methods: Multiple tools, including TIMER2.0, Oncomine, GEPIA2, UALCAN, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, and MethSurv, etc. were applied to comprehensively analyze the expression, genetic alternations, clinicopathological relevance, prognostic value, and DNA methylation of , along with its correlations with immune infiltration in HCC. Besides, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analysis were performed for the correlated genes of , closely interconnected clusters and hub proteins in the PPI network were discovered to learn the underlying biological mechanisms.

Results: We found was significantly upregulated in diverse cancers including HCC, compared with the corresponding normal controls. upregulation was significantly associated with unfavorable clinicopathological features and survivals of HCC patients. Genetic alternations of frequently occurred, which were linked to worse outcomes of HCC patients. The results of GSEA displayed and its correlated genes might be components of condensed chromosomes and spindles, which participated in biological processes and signaling pathways involving DNA replication, cytokinesis, and cell cycle checkpoint, etc. Three highly interconnected clusters and 10 hub proteins were identified from the PPI network constructed with the correlated genes of . Moreover, expression was found positively correlated with infiltration levels of various immune cells, especially myeloid-derived suppressor cells.

Conclusion: This study demonstrated might be a promising unfavorable prognostic biomarker and a therapeutic target of HCC, which could regulate HCC progression through cell division and immunosuppression.
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http://dx.doi.org/10.2147/IJGM.S340057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566006PMC
October 2021

Bone mesenchymal stem cells-derived miR-223-3p-containing exosomes ameliorate lipopolysaccharide-induced acute uterine injury via interacting with endothelial progenitor cells.

Bioengineered 2021 Nov 5. Epub 2021 Nov 5.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University.

Bone mesenchymal stem cells (BMSCs) have been used for the treatment of acute uterine injury (AUI)-induced intrauterine adhesion (IUA) via interacting with the endothelial progenitor cells (EPCs), and BMSCs-derived exosomes (BMSCs-exo) may be the key regulators for this process. However, the underlying mechanisms have not been studied. Based on the existed literatures, lipopolysaccharide (LPS) was used to induce AUI in mice models and EPCs to mimic the realistic pathogenesis of IUA and . Our data suggested that LPS induced apoptotic and pyroptotic cell death in mice uterine horn tissues and EPCs, and the clinical data supported that increased levels of pro-inflammatory cytokines IL-18 and IL-1β were also observed in IUA patients' serum samples, and silencing of NLRP3 rescued cell viability in LPS-treated EPCs. Next, the LPS-treated EPCs were respectively co-cultured with BMSCs in the Transwell system and BMSCs-exo, and the results hinted that both BMSCs and BMSCs-exo reversed the promoting effects of LPS treatment-induced cell death in EPCs. Then, we screened out miR-223-3p, as the upstream regulator for NLRP3, was enriched in BMSCs-exo, and BMSCs-exo inactivated NLRP3-mediated cell pyroptosis in EPCs via delivering miR-223-3p. Interestingly, upregulation of miR-223-3p attenuated LPS-induced cell death in EPCs. Collectively, we concluded that BMSCs-exo upregulated miR-223-3p to degrade NLRP3 in EPCs, which further reversed the cytotoxic effects of LPS treatment on EPCs to ameliorate LPS-induced AUI.
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http://dx.doi.org/10.1080/21655979.2021.2001185DOI Listing
November 2021

Serial assessment of measurable residual disease in medulloblastoma liquid biopsies.

Cancer Cell 2021 Nov 21;39(11):1519-1530.e4. Epub 2021 Oct 21.

Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.
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http://dx.doi.org/10.1016/j.ccell.2021.09.012DOI Listing
November 2021

GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

Int J Chron Obstruct Pulmon Dis 2021;16:2817-2832. Epub 2021 Oct 8.

Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Background: Chronic obstructive pulmonary disease (COPD) is a major health problem associated with high mortality worldwide. Cigarette smoke (CS) exposure is the main cause of COPD. Glioma pathogenesis-related protein 1 (GLIPR1) plays a key role in cell growth, proliferation, and invasion; however, the role of GLIPR1 in COPD remains unclear.

Methods: To clarify the involvement of GLIPR1 in COPD pathogenesis, Glipr1 knockout (Glipr1-/-) mice were generated. Wild-type (WT) and Glipr1-/- mice were challenged with CS for 3 months. To illustrate how GLIPR1 regulates CS-induced airway damage, knockdown experiments targeting GLIPR1 and PLAU, as well as overexpression experiments of PLAU, were performed with human bronchial epithelial cells.

Results: Compared with WT mice, Glipr1-/- mice showed exacerbated CS-induced airway damage including lung inflammation, airway wall thickening, and alveolar destruction. After CS exposure, total proteins, total white cells, neutrophils, lymphocytes, IL-6, and matrix metalloproteinase-9 increased significantly in lung of Glipr1-/- mice than those in lung of WT mice. Furthermore, in vivo and in vitro experiments demonstrated that silencing of GLIPR1 inactivated PLAU/EGFR signaling and promoted caspase-1-dependent pyroptosis (a mode of inflammatory cell death) induced by CS and CS extract exposure, respectively. In vitro experiments further revealed the interaction between GLIPR1 and PLAU, and silencing of PLAU blocked EGFR signaling and promoted pyroptosis, while overexpression of PLAU activated EGFR signaling and reversed pyroptosis.

Conclusion: To conclude, GLIPR1 played a pivotal role in COPD pathogenesis and protected against CS-induced inflammatory response and airway damage, including cell pyroptosis, through the PLAU/EGFR signaling. Thus, GLIPR1 may play a potential role in COPD treatment.
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http://dx.doi.org/10.2147/COPD.S328313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517531PMC
November 2021

Lanthanum-loaded peanut shell biochar prepared via one-step pyrolysis method for phosphorus removal and immobilization.

Environ Technol 2021 Nov 13:1-10. Epub 2021 Nov 13.

Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu, People's Republic of China.

Phosphorus (P) is a nutrient element triggering eutrophication. Therefore, the removal of excess phosphorus has become an emergent demand. In this study, lanthanum-loaded biochar (La-BC) was prepared via a simple one-step pyrolysis method. Its surface properties and structural characteristics were analyzed by SEM, XRD, FTIR and pH. The phosphate removal by the La-BC was systematically investigated in batch mode. Results showed that the phosphorus adsorption obeyed the pseudo-second-order model and Langmuir isotherm. The calculated maximum adsorption capacities were 31.94, 33.06 and 33.98 mg/g at 25, 35 and 45°C, respectively. Except for SO and CO, phosphate adsorption by the La-BC showed strong anti-interference to coexisting ions. For real water samples, the phosphate concentrations in the effluents were below 0.02 mg/L after treatment. The P loaded the La-BC was difficult to be desorbed, suggesting that the La-BC was not only a P-capping agent but also a P-immobilizing agent. More interestingly, a large number of stable LaPO nanofibers were formed on the La-BC surface via the reaction between the dissolved phosphate anions and La(OH) loaded on the adsorbent. Their intertwining facilitated the formation of the floc, which was conducive to the solid-liquid separation. Hence, the developed La-BC can be used as a potential adsorbent for natural waterbody remediation.
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http://dx.doi.org/10.1080/09593330.2021.1996468DOI Listing
November 2021

Competitive Wetting: A New Approach to Prevent Liquid Penetration through Porous Materials with Superior Synergistic Effect.

Small 2021 Oct 8:e2103695. Epub 2021 Oct 8.

Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, Innovation Campus. Squires Way, North Wollongong, NSW, 2500, Australia.

Blocking liquid penetration in porous materials is a key function for several applications including chemical protective clothing (CPC), wound healing, and hygiene products. Enormous efforts are made to prevent liquid penetration through porous media by the modification of materials. CPC is used as an example to demonstrate the effect of the synergistic effect on liquid penetration. A common strategy to achieve liquid protection is the use of liquid-repellent surfaces with the aid of a liquid absorption liner layer. However, this strategy demonstrates limited success for low surface energy liquids. Herein, a novel approach is reported to prevent the permeation of liquid across porous materials by a synergistic effect. Both fabrics are individually susceptible to be wetted by low surface tension liquids. However, when they are assembled, they can prevent low surface tension liquids from penetrating because of the wettability gap between the two fabrics. The fabric assembly demonstrates an increase in the liquid prevention capacity by 70-1000 times compared with a commercial CPC material. This novel synergistic effect may offer a breakthrough in the development of various applications including protective clothing baby nappies, hygiene products, food preparation, soil water retention, and sporting/camping/ski equipment and clothing.
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http://dx.doi.org/10.1002/smll.202103695DOI Listing
October 2021

Treatment of nevus of Ota with 1064 nm picosecond Nd:YAG laser: A retrospective study.

Dermatol Ther 2021 Oct 5:e15152. Epub 2021 Oct 5.

Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.

Nevus of Ota has been successfully treated by lasers. Currently, 1064 nm picosecond Nd:YAG lasers have become available for the treatment of pigmented disorders. However, there are few studies concerning the application of 1064 nm picosecond Nd:YAG laser in nevus of Ota. This study aimed to evaluate the efficacy and safety of a 1064 nm picosecond Nd:YAG laser for the treatment of nevus of Ota. We conducted a retrospective analysis of Chinese patients with nevus of Ota who had been treated with a 1064 nm picosecond Nd:YAG laser. Those who had any other laser treatment during the period of picosecond laser treatment were excluded. Via a visual analog scale for percentage of pigmentary clearance in standard photographs, the treatment efficacy was assessed by three blinded physician evaluators. A total of 16 subjects were included in this retrospective study. The average age at the beginning of treatment was 16.87 years old (range of 4 months to 59 years), and all patients were of Fitzpatrick skin type IV. Total treatment ranged from 1 to 5 sessions. A 1064 nm picosecond Nd:YAG laser with a mean fluence of 1.8-4.3 J/cm was used at 3-12 month intervals. The mean efficacy score for all 16 patients was 2.56 after one session, and the mean efficacy score of 13 patients who completed two sessions and nine patients who completed three sessions were 3.15 and 3.51, respectively. Postinflammatory hyperpigmentation after treatment was only observed in 1 (1/16, 6.25%) patient. The 1064 nm picosecond Nd:YAG laser is an effective and safe approach for treating nevus of Ota.
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http://dx.doi.org/10.1111/dth.15152DOI Listing
October 2021

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma.

Nat Commun 2021 09 20;12(1):5531. Epub 2021 Sep 20.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.
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http://dx.doi.org/10.1038/s41467-021-25709-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452624PMC
September 2021

Qingfei Paidu Decoction for COVID-19: A Bibliometric Analysis.

Biomed Environ Sci 2021 09;34(9):755-760

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

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http://dx.doi.org/10.3967/bes2021.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485524PMC
September 2021

Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.

Nat Genet 2021 09 2;53(9):1300-1310. Epub 2021 Sep 2.

Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.
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http://dx.doi.org/10.1038/s41588-021-00913-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432599PMC
September 2021

A surface-based calibration approach to enable dynamic and accurate quantification of colorimetric assay systems.

Anal Methods 2021 09 30;13(37):4290-4297. Epub 2021 Sep 30.

Department of Biomedical Engineering, Florida International University, 10555 W Flagler St, EC 2612, Miami, FL, 33174, USA.

Colorimetry is widely used in assay systems for its low-cost, ease-of-use, rapidity, moderate storage requirements and intuitively visible effects. However, the application is limited due to its relatively low sensitivity. Conventional colorimetric calibration methods often use a fixed incubation time that can limit the detection range, system robustness and sensitivity. In this paper, we used color saturation to measure the accumulation of product (correlation coefficient = 0.9872), and we created a novel "calibration mesh" method based on an expanded sigmoid function to enhance sensitivity. The novel calibration mesh method can be adapted for a wide variety of assay systems to improve robustness and detection range, and provide a dynamic and faster output.
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http://dx.doi.org/10.1039/d1ay01130hDOI Listing
September 2021

Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis.

Mol Med 2021 08 19;27(1):90. Epub 2021 Aug 19.

Department of Cardiology, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, People's Republic of China.

Background: It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown.

Methods: Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis.

Results: We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCKR) mediated the protective effect of gastrin since the CCKR blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection.

Conclusion: Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.
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http://dx.doi.org/10.1186/s10020-021-00352-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375043PMC
August 2021

DNA dynamics and computation based on toehold-free strand displacement.

Nat Commun 2021 08 17;12(1):4994. Epub 2021 Aug 17.

School of Life Sciences, Tsinghua University-Peking University Center for Life Sciences, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.

We present a simple and effective scheme of a dynamic switch for DNA nanostructures. Under such a framework of toehold-free strand displacement, blocking strands at an excess amount are applied to displace the complementation of specific segments of paired duplexes. The functional mechanism of the scheme is illustrated by modelling the base pairing kinetics of competing strands on a target strand. Simulation reveals the unique properties of toehold-free strand displacement in equilibrium control, which can be leveraged for information processing. Based on the controllable dynamics in the binding of preformed DNA nanostructures, a multi-input-multi-output (MIMO) Boolean function is controlled by the presence of the blockers. In conclusion, we implement two MIMO Boolean functions (one with 4-bit input and 2-bit output, and the other with 16-bit input and 8-bit output) to showcase the controllable dynamics.
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http://dx.doi.org/10.1038/s41467-021-25270-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371076PMC
August 2021

Neuronal Trafficking of the Amyloid Precursor Protein-What Do We Really Know?

Biomedicines 2021 Jul 10;9(7). Epub 2021 Jul 10.

Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 17164 Stockholm, Sweden.

Alzheimer's disease (AD) is the most common type of dementia, contributing to 60-80% of cases. It is a neurodegenerative disease that usually starts symptomless in the first two to three decades and then propagates into a long-term, irreversible disease, resulting in the progressive loss of memory, reasoning, abstraction and language capabilities. It is a complex disease, involving a large number of entangled players, and there is no effective treatment to cure it or alter its progressive course. Therefore, a thorough understanding of the disease pathology and an early diagnosis are both necessary. AD has two significant pathological hallmarks: extracellular senile plaques composed of amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and the aggregation of Aβ, which starts in earlier stages, is usually claimed to be the primary cause of AD. Secretases that cleave Aβ precursor protein (APP) and produce neurotoxic Aβ reside in distinct organelles of the cell, and current concepts suggest that APP moves between distinct intracellular compartments. Obviously, APP transport and processing are intimately related processes that cannot be dissociated from each other, and, thus, how and where APP is transported determines its processing fate. In this review, we summarize critical mechanisms underlying neuronal APP transport, which we divide into separate parts: (1) secretory pathways and (2) endocytic and autophagic pathways. We also include two lipoprotein receptors that play essential roles in APP transport: sorting-related receptor with A-type repeats and sortilin. Moreover, we consider here some major disruptions in the neuronal transport of APP that contribute to AD physiology and pathology. Lastly, we discuss current methods and technical difficulties in the studies of APP transport.
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http://dx.doi.org/10.3390/biomedicines9070801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301342PMC
July 2021

HO-1 nuclear accumulation and interaction with NPM1 protect against stress-induced endothelial senescence independent of its enzymatic activity.

Cell Death Dis 2021 07 26;12(8):738. Epub 2021 Jul 26.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, China.

Heme oxygenase-1 (HO-1) has attracted accumulating attention for its antioxidant enzymatic activity. However, the exact regulatory role of its non-enzymatic activity in the cardiovascular system remains unaddressed. Here, we show that HO-1 was accumulated in the nuclei of stress-induced senescent endothelial cells, and conferred protection against endothelial senescence independent of its enzymatic activity. Overexpression of ΔHO-1, a truncated HO-1 without transmembrane segment (TMS), inhibited HO-induced endothelial senescence. Overexpression of ΔHO-1, the catalytically inactive form of ΔHO-1, also exhibited anti-senescent effect. In addition, infection of recombinant adenovirus encoding ΔHO-1 with three nuclear localization sequences (NLS), alleviated endothelial senescence induced by knockdown of endogenous HO-1 by CRISPR/Cas9. Moreover, repression of HO-1 nuclear translocation by silencing of signal peptide peptidase (SPP), which is responsible for enzymatic cleavage of the TMS of HO-1, exacerbated endothelial senescence. Mechanistically, nuclear HO-1 interacted with NPM1 N-terminal portion, prevented NPM1 translocation from nucleolus to nucleoplasm, thus disrupted NPM1/p53/MDM2 interactions and inhibited p53 activation by NPM1, finally resisted endothelial senescence. This study provides a novel understanding of HO-1 as a promising therapeutic strategy for vascular senescence-related cardiovascular diseases.
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http://dx.doi.org/10.1038/s41419-021-04035-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313700PMC
July 2021

Non-high-density lipoprotein cholesterol and mortality among peritoneal dialysis patients.

J Clin Lipidol 2021 Jul 3. Epub 2021 Jul 3.

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Key Laboratory of Nephrology, National Health Commission and Guangdong Province, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address:

Background: The association between non-high-density lipoprotein cholesterol (non-HDL-C) and mortality in patients undergoing peritoneal dialysis (PD) is unclear.

Objective: The aim of this study was to evaluate the association of non-HDL-C with cardiovascular (CV) and all-cause mortality in PD patients.

Methods: We conducted a prospective cohort study. A total of 1,616 incident PD patients from a single PD center in South China were followed for a median of 47.6 months. The independent association of non-HDL-C with CV and all-cause mortality was evaluated by a Cox regression analysis.

Results: During the follow-up period, 508 (31.4%) patients died, of which 249 (49.0%) were due to CV events. Atherosclerotic CV mortality accounted for 59.8% of CV mortality. In multivariable models, for 1-SD increase in non-HDL-C level, the hazard ratios (HRs) for CV and all-cause mortality were 1.52  [95% confidence interval (CI), 1.32-1.75; P < 0.001)] and 1.24 (95% CI, 1.12-1.39; P < 0.001), respectively. Furthermore, non-HDL-C was positively associated with atherosclerotic CV mortality (HR, 1.29; 95% CI, 1.09-1.52; P = 0.004) but not associated with nonatherosclerotic CV mortality (HR, 0.79; 95% CI, 0.59-1.05; P = 0.108). The quartile analyses showed a similar pattern to the continuous variable analyses of non-HDL-C levels for CV and all-cause mortality but did not demonstrate statistical significance for atherosclerotic or nonatherosclerotic CV mortality.

Conclusion: An elevated non-HDL-C level was independently associated with an increased risk of CV mortality, especially atherosclerotic CV mortality, and all-cause mortality in incident PD patients.
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http://dx.doi.org/10.1016/j.jacl.2021.06.005DOI Listing
July 2021

Population Pharmacokinetic Model Development and Simulation for Recombinant Erwinia Asparaginase Produced in Pseudomonas fluorescens (JZP-458).

Clin Pharmacol Drug Dev 2021 Jul 26. Epub 2021 Jul 26.

Jazz Pharmaceuticals, Palo Alto, California, USA.

JZP-458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme expected to lack immunologic cross-reactivity to Escherichia coli-derived asparaginases. It is being developed as part of a multiagent chemotherapeutic regimen to treat acute lymphoblastic leukemia or lymphoblastic lymphoma patients who develop E coli-derived asparaginase hypersensitivity. A population pharmacokinetic (PopPK) model was developed for JZP-458 using serum asparaginase activity (SAA) data from a phase 1, single-dose study (JZP458-101) in healthy adults. Effects of intrinsic covariates (body weight, body surface area, age, sex, and race) on JZP-458 PK were evaluated. The model included SAA data from 24 healthy adult participants from the phase 1 study who received JZP-458: intramuscular (IM) data at 12.5 mg/m (N = 6) and 25 mg/m (N = 6), and intravenous (IV) data at 25 mg/m (N = 6) and 37.5 mg/m (N = 6). Model simulations of adult and pediatric SAA profiles were performed to explore the likelihood of achieving a therapeutic target nadir SAA (NSAA) level ≥0.1 IU/mL based on different administration strategies. PopPK modeling and simulation suggest JZP-458 is expected to achieve 72-hour NSAA levels ≥0.1 IU/mL in 100% of adult or pediatric populations receiving IM administration at 25 mg/m , and in 80.9% of adult and 94.5% of pediatric populations receiving IV administration at 37.5 mg/m on a Monday/Wednesday/Friday (M/W/F) dosing schedule. Based on these results, the recommended starting dose for the phase 2/3 pivotal study is 25 mg/m IM or 37.5 mg/m IV on a M/W/F dosing schedule in pediatric and adult patients.
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http://dx.doi.org/10.1002/cpdd.1002DOI Listing
July 2021

Corrigendum to "Acupuncture for diabetic peripheral neuropathy: An overview of systematic reviews" [Compl. Ther. Clin. Pract., Volume 43, (May 2021), 101375].

Complement Ther Clin Pract 2021 Aug 12;44:101435. Epub 2021 Jul 12.

The First School of Clinical Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:

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http://dx.doi.org/10.1016/j.ctcp.2021.101435DOI Listing
August 2021

Recurrent Wheezing and Asthma After Respiratory Syncytial Virus Bronchiolitis.

Front Pediatr 2021 4;9:649003. Epub 2021 Jun 4.

Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Respiratory syncytial virus (RSV) is the most common pathogen of acute bronchiolitis in children, which sometimes triggers the development of recurrent wheezing and increases the risk of childhood asthma. We enrolled 425 children who were diagnosed with RSV-infected bronchiolitis at the department of pulmonology, Children's Hospital Zhejiang University School of Medicine in 2011. Long-term follow-up was performed to explore the consequence of bronchiolitis on subsequent recurrent wheezing and asthma. Of 425 patients, 266 cases completed the entire follow-up, the mean age of onset was 4.9 (3.3) months, and the male-to-female ratio was 2.5. The mean birth weight of all patients was 3.22 (0.63) kg, and the number of patients who had a history of cesarean section was 148. According to the outcome of follow-up, 36 were in the recurrent wheezing (RW) group, 65 were in the asthma (AS) group, and the remaining 165 were in the completely recovered (CR) group. The age of onset was older and the birth weights were higher in the AS group than those in the CR group ( < 0.05). And the higher proportion of cesarean sections was higher in the RW group than that in the CR group ( < 0.05). Furthermore, we found a remarkable increasing of serum IgE in the AS groups than that in the CR group ( < 0.01). Multiple logistic regression analysis showed that the cesarean section was the risk factor for the development of recurrent wheezing and the higher birth weight was the risk factor for the development of asthma. RSV bronchiolitis might increase the incidence of recurrent wheezing and asthma. Allergic constitution was an important prerequisite for the occurrence of asthma, and related risk factor such as cesarean section can only increase recurrent wheezing to a certain extent within a certain period of time. And we also find higher birth weight and older onset age for those who develop asthma, which should be verified in the future.
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http://dx.doi.org/10.3389/fped.2021.649003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211724PMC
June 2021

Large-Scale Identification of T-Cell Epitopes Derived From Severe Acute Respiratory Syndrome Coronavirus 2 for the Development of Peptide Vaccines Against Coronavirus Disease 2019.

J Infect Dis 2021 09;224(6):956-966

Department of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen International Biological Valley-Life Science Industrial Park, Dapeng New District, Shenzhen, China.

Background: Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19.

Methods: In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using peripheral blood mononuclear cells from unexposed individuals (negative for SARS-CoV-2 immunoglobulin G).

Results: Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. It is interesting to note that most (5 of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations.

Conclusions: In summary, in the current study, we present an alternative and effective strategy for the identification of T-cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.
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http://dx.doi.org/10.1093/infdis/jiab324DOI Listing
September 2021

Next Generation Sequencing-Based Identification of T-Cell Receptors for Immunotherapy Against Hepatocellular Carcinoma.

Hepatol Commun 2021 Jun 28;5(6):1106-1119. Epub 2021 Feb 28.

Department of Research and Development Shenzhen Institute for Innovation and Translational Medicine Shenzhen International Biological Valley-Life Science Industrial Park Shenzhen China.

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a global health concern, and HBV proteins may be ideal targets for T cell-based immunotherapy for HCC. There is a need for fast and efficient identification of HBV-specific T cell receptors (TCRs) for the development of TCR-transduced T (TCR-T) cell-based immunotherapy. Two widely employed TCR identification approaches, T cell clonal expansion and single-cell sequencing, involve a TCR singularization process for the direct identification of Vα and Vβ pairs of TCR chains. Clonal expansion of T cells is well known to have tedious time and effort requirements due to the use of T cell cultures, whereas single-cell sequencing is limited by the requirements of cell sorting and the preparation of a single-cell immune-transcriptome library as well as the massive cost of the whole procedure. Here, we present a next-generation sequencing (NGS)-based HBV-specific TCR identification that does not require the TCR singularization process. : Two pairing strategies, ranking-based strategy and α-β chain mixture-based strategy, have proved to be useful for NGS-based TCR identification, particularly for polyclonal T cells purified by a peptide-major histocompatibility complex (pMHC) multimer-based approach. Functional evaluation confirmed the specificity and avidity of two identified HBV-specific TCRs, which may potentially be used to produce TCR-T cells to treat patients with HBV-related HCC.
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http://dx.doi.org/10.1002/hep4.1697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183181PMC
June 2021

Human Gastric Cancer Stem Cell (GCSC) Markers Are Prognostic Factors Correlated With Immune Infiltration of Gastric Cancer.

Front Mol Biosci 2021 25;8:626966. Epub 2021 May 25.

Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.

The prognosis of patients with gastric cancer (GC) is still unsatisfying. Numerous markers of gastric cancer stem cells (GCSCs) have been identified and were thought to be related to cancer aggressiveness. However, the roles of GCSC markers in GC patients' prognosis and immune infiltration remain unknown. Expression of GCSC markers was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). Their associations with clinicopathological parameters were analyzed using UALCAN and LinkedOmics. Alternations and protein expression of GCSC markers were analyzed by cBioPortal and the Human Protein Atlas databases, respectively. The prognostic significance of GCSC markers was evaluated using Kaplan-Meier plotter. Correlations between the expression of GCSC markers and immune infiltration along with biomarkers of tumor-infiltrating immune cells (TIICs) were assessed combined Tumor Immune Estimation Resource and GEPIA. GeneMANIA was used to discover the interactive genes of GCSC markers, and enrichment analysis was performed using Database for Annotation, Visualization, and Integrated Discovery server. We identified six GCSC markers significantly up-expressed in GC, compared with normal stomach tissues. Among them, the overexpression of , , and significantly indicated adverse, while indicated beneficial clinicopathological features of GC patients. The up-regulation of showed unfavorable prognostic significance, whereas and showed the opposite. The six GCSC markers were all correlated with the infiltration and activation of distinct TIICs. Especially, , , and showed strongly positive correlations with tumor-associated macrophages. Besides, chemokine, Toll-like receptor, NF-kappa B, and HIF-1 signaling pathways might be involved in the regulation of GCSC markers on cancer development. This study proposed that GCSC markers might be promising targets of GC treatment to weaken cancer stem-like properties and strengthen anticancer immunity.
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http://dx.doi.org/10.3389/fmolb.2021.626966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185345PMC
May 2021

Fabrics with Novel Air-Oil Amphibious, Spontaneous One-Way Water-Transport Capability for Oil/Water Separation.

ACS Appl Mater Interfaces 2021 Jun 8;13(24):29150-29157. Epub 2021 Jun 8.

College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Porous media with directional water-transport capability have great applications in oil-water separation, moisture-harvesting, microfluidics, and moisture-management textiles. However, the previous directional water-transport materials chiefly work in the air. The materials with directional water-transport capability in the oil phase have been less reported. Here, we fabricated a novel Janus fabric with amphibious directional water-transport capability that can work both in the air and oil phases. It was prepared using dip coating and spraying to develop an oleophobic-hydrophobic to oleophobic-hydrophilic gradient across the thickness of the fabric substrate. The fabric allowed water droplets to rapidly transport from the hydrophobic to the hydrophilic side when the fabric was either in the air environment or fully immersed in oil. However, it hindered water transport in the opposite direction. More importantly, the fabric can overcome gravity to capture water from oil. Such an air-oil amphibious water-transport fabric showed excellent water collecting capability. In oil, it does not require any prewetting or extra pressure to perform directional water transport, which is vital for water-oil separation and microfluidics. Such amphibious directional water-transport function may be useful for the development of smart membranes and directional liquid delivery.
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http://dx.doi.org/10.1021/acsami.1c06489DOI Listing
June 2021

CXCL2/10/12/14 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma.

Biosci Rep 2021 06;41(6)

Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.

Background: C-x-C motif chemokine ligands (CXCLs) are critical regulators of cancer immunity and angiogenesis, which affect disease progression and treatment responses. The character of each CXCL in the prognosis and immune infiltration of hepatocellular carcinoma (HCC) patients is unclear yet.

Methods: Differentially expressed CXCLs between HCC and normal control were screened by Oncomine and GEPIA2. Genetic alternations of CXCLs in HCC were analyzed by cBioPortal. Clinicopathological relevance of CXCLs in HCC patients was analyzed using UALCAN. The prognostic value of CXCLs was evaluated using univariate and multivariate analyses. Correlations of CXCLs' expression with immune infiltration, chemokines and their receptors were assessed integrating TIMER, TISIDB, and GEPIA2. The co-expressed genes of CXCLs were discovered, and functional enrichment analysis was performed for them.

Results: CXCL9/10 was significantly higher expressed while CXCL2/12/14 was lower expressed in HCC than normal tissues, but they didn't show significant clinicopathological relevance in HCC patients. High-expression of CXCL2/10/12/14 indicated favorable outcomes of HCC patients. The expression of CXCL9/10/12/14 was significantly positively correlated with not only the infiltration and biomarkers' expression of various tumor-infiltrating immune cells but also the abundance of chemokines and their receptors. The co-expressed genes of the five CXCLs were extracellular components and regulated immune or inflammatory responses and signaling pathways of chemokine, Toll-like receptor and tumor necrosis factor might be involved.

Conclusion: The present study proposed CXCL2/10/12/14 might predict outcomes of HCC patients and were extensively related with the immune microenvironment in HCC. It would be a prospective therapeutic strategy for HCC to enhance effective immunity surveillance through intervening in these CXCLs.
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http://dx.doi.org/10.1042/BSR20204312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217985PMC
June 2021

Hydrazide-assisted directional antibody conjugation of gold nanoparticles to enhance immunochromatographic assay.

Anal Chim Acta 2021 Jul 7;1168:338623. Epub 2021 May 7.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, PR China; School of Food Science and Technology, Nanchang University, Nanchang, 330031, PR China; Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang, 330047, PR China. Electronic address:

The analytical performance of immunochromatographic assay (ICA) is usually determined by the biological activity of antibody and gold nanoparticle conjugates (AuNP probes). However, conventional probes are constructed using the nondirectional coupling method that can cause the improper orientation of antibodies with the poor accessibility of antigen-binding sites. To address these issues, we report a site-specific directional coupling strategy to enhance the bioactivity of AuNP probes through the specific covalent binding of the aldehyde group in the Fc domain of antibodies with the hydrazide group modified on the surface of AuNPs. Through this design, the antibodies can be erected on the AuNP surface to fully expose the Fab domain and achieve the maximized functional availability. Leveraging these AuNP probes as ICA labels, we demonstrate an improved detection of the hepatitis B surface antigen with less used amount of labeled antibody (0.2 mg/pmol AuNPs), shorter reaction time (10 min), better antibody bioactivity, and higher detection sensitivity (2 ng/mL) compared with the carbodiimide method. Overall, this work provides great promise for the design and the construction of high-performance probes to enhance the detection performance of ICA sensors.
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http://dx.doi.org/10.1016/j.aca.2021.338623DOI Listing
July 2021

Construction and Evaluation of a Deep Learning Model for Assessing Acne Vulgaris Using Clinical Images.

Dermatol Ther (Heidelb) 2021 Aug 18;11(4):1239-1248. Epub 2021 May 18.

Hospital of Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, People's Republic of China.

Introduction: Accurate assessment is the basis for the effective treatment of acne vulgaris. The goal of this study was to achieve standardised diagnosis and treatment based on a deep learning model that was developed according to the current Chinese Guidelines for the Management of Acne Vulgaris.

Methods: The first step was to divide each image of acne vulgaris into four regions. Each of these four regions of the same patient was then combined to form a complete facial region. The second step was to classify the images based lesion type, in accordance with the current Chinese guidelines, and by treatment strategy adopted by experienced dermatologists. The final step was to evaluate the performance of the deep learning model in patients with acne vulgaris.

Results: The results showed that the average F1 value of the assessment model is 0.8 (optimum value = 1). The weighted kappa coefficient between the evaluation according to the artificial intelligence model and the evaluation by the attending dermatologists was 0.791 (95% confidence interval 0.671-0.910, P < 0.001), indicating a high degree of consistency.

Conclusions: The assessment model based on deep learning and according to the Chinese guidelines had a slightly higher overall performance is comparable to that of the attending dermatologist.
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http://dx.doi.org/10.1007/s13555-021-00541-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322224PMC
August 2021

Network Pharmacology-Based Investigation of the Therapeutic Mechanisms of Action of Danning Tablets in Nonalcoholic Fatty Liver Disease.

Evid Based Complement Alternat Med 2021 27;2021:3495360. Epub 2021 Apr 27.

Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen 518033, China.

Nonalcoholic fatty liver disease (NAFLD) is a rising global public health concern due to its prevalence. Danning Tablets (DNt), a composite prescription of Chinese herbal medicine, shows significant curative effects on NAFLD in clinical application. This study aimed to decipher the bioactive substances and potential mechanisms of action of DNt in the treatment of NAFLD, applying an integrated network pharmacology approach. First, the bioactive compounds of DNt were screened based on their pharmacokinetic properties, and the corresponding drug targets were predicted. Then, the NAFLD-related targets were collected. The overlapping targets between the putative targets of DNt and NAFLD-related targets were identified as the potential therapeutic targets of DNt against NAFLD. Subsequently, the networks were constructed and analyzed, and the key bioactive compounds and targets were screened out depending on their importance in the networks. Functional enrichment analysis was carried out to elucidate the potential mechanisms of DNt acting on NAFLD. Finally, a molecular docking simulation was implemented to assess the potential binding affinity between the key targets and the bioactive compounds. As a result, 43 bioactive compounds of DNt and 69 putative targets were identified. Based on the network analysis, we found seven key bioactive compounds (quercetin, -sitosterol, luteolin, kaempferol, supraene, curcumenolactone C, and stigmasterol) of DNt might treat NAFLD via intervening IL6, MAPK8, VEGFA, CASP3, ALB, APP, MYC, PPARG, and RELA. The functional enrichment analysis revealed that DNt might affect NAFLD by modulating the signaling pathways involved in lipid metabolism, inflammation, oxidation, insulin resistance (IR), atherosclerosis, and apoptosis. Furthermore, most key bioactive compounds might bind firmly with the key targets. This study predicted the multicomponent, multitarget, and multipathway mechanisms of DNt in the treatment of NAFLD from a holistic perspective. DNt could be a promising agent for NAFLD, but further experimental verifications are still needed.
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http://dx.doi.org/10.1155/2021/3495360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096548PMC
April 2021
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