Publications by authors named "Kun Li"

1,310 Publications

  • Page 1 of 1

Inter-subject variation in ACE2 protein expression in human airway epithelia and its relationship to SARS-CoV-2 infection.

J Infect Dis 2021 Jul 21. Epub 2021 Jul 21.

Department of Pediatrics and Microbiology and Immunology, University of Iowa, Iowa City, IA, 52242, USA.

SARS-CoV-2 initiates entry into airway epithelia by binding its receptor, ACE2. To explore whether inter-individual variation in ACE2 abundance contributes to variability in COVID-19 outcomes, we measured ACE2 protein abundance in primary airway epithelial cultures derived from 58 human donor lungs. We found no evidence for sex- or age-dependent differences in ACE2 protein expression. Further, we found that variations in ACE2 abundance had minimal effects on viral replication and induction of the interferon response in airway epithelia infected with SARS-CoV-2. Our results highlight the relative importance of additional host factors, beyond viral receptor expression, in determining COVID-19 lung disease outcomes.
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http://dx.doi.org/10.1093/infdis/jiab383DOI Listing
July 2021

Isolation and characterization of porcine monoclonal antibodies revealed two distinct serotype-independent epitopes on VP2 of foot-and-mouth disease virus.

J Gen Virol 2021 Jul;102(7)

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou 730046, PR China.

Pigs are susceptible to foot-and-mouth disease virus (FMDV), and the humoral immune response plays an essential role in protection against FMDV infection. However, little information is available about FMDV-specific mAbs derived from single B cells of pigs. This study aimed to determine the antigenic features of FMDV that are recognized by antibodies from pigs. Therefore, a panel of pig-derived mAbs against FMDV were developed using fluorescence-based single B cell antibody technology. Western blotting revealed that three of the antibodies (1C6, P2-7E and P2-8G) recognized conserved antigen epitopes on capsid protein VP2, and exhibited broad reactivity against both FMDV serotypes A and O. An alanine-substitution scanning assay and sequence conservation analysis elucidated that these porcine mAbs recognized two conserved epitopes on VP2: a linear epitope (KKTEETTLL) in the N terminus and a conformational epitope involving residues K63, H65, L66, F67, D68 and L81 on two β-sheets (B-sheet and C-sheet) that depended on the integrity of VP2. Random parings of heavy and light chains of the IgGs confirmed that the heavy chain is predominantly involved in binding to antigen. The light chain of porcine IgG contributes to the binding affinity toward an antigen and may function as a support platform for antibody stability. In summary, this study is the first to reveal the conserved antigenic profile of FMDV recognized by porcine B cells and provides a novel method for analysing the antibody response against FMDV in its natural hosts (i.e. pigs) at the clonal level.
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http://dx.doi.org/10.1099/jgv.0.001608DOI Listing
July 2021

Sanxiapeptin, a linear pentapeptide from Penicillium oxalicum, inhibited the growth of citrus green mold.

Food Chem 2021 Jul 5;366:130541. Epub 2021 Jul 5.

Hubei Key Laboratory of Natural Products Research and Development, College of Life Science and Pharmacy, China Three Gorges University, Yichang 443002, China; Key Laboratory of Functional Yeast in National Light Industry, College of Life Science and Pharmacy, China Three Gorges University, Yichang 443002, China. Electronic address:

Penicillium oxalicum has been used as a biocontrol fungus in agriculture for many years, but the antimicrobial substances are still uncertain. Herein, we isolated a linear peptide named Sanxiapeptin in the culture broth of Penicillium oxalicum SG-4 collecting from the Three Gorges riparian zone. Sanxiapeptin exhibited potent inhibitory effect on citrus green mold Penicillium digitatum, the main fungi responsible for postharvest decay. Sanxiapeptin was elucidated as composing of five amino acids, which were β-amino-α-methoxybutyric acid (Amoba), N-Me-l-Thr, d-Thr, N-Me-l-Val and l-Ser. By analyzing three chemically synthesized oligopeptides with similar structures, we found that the first amino acid of Amoba was crucial to the antifungal activity, as was the methylation of peptide bond. Sanxiapeptin may act as an antimicrobial agent by affecting the function of cell membranes or walls. The antimicrobial spectrum, safety and stability analysis supported that Sanxiapeptin was a promising antifungal agent for citrus preservation.
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http://dx.doi.org/10.1016/j.foodchem.2021.130541DOI Listing
July 2021

Doubling the optical efficiency of VR systems with a directional backlight and a diffractive deflection film.

Opt Express 2021 Jun;29(13):20673-20686

We demonstrate an approach to double the optical efficiency of virtual reality (VR) systems based on a directional backlight and a diffractive deflection film (DDF). The directional backlight consists of a commercial collimated light-emitting diode (LED) array and a two-layer privacy film, while the DDF is a three-domain Pancharatnam-Berry (PB) phase lens. Such a PB phase lens was fabricated by the zone exposure and spin-coating method. The focal length of each domain is designed according to the imaging optics of the VR system. Our approach works well in both Fresnel and "pancake" VR systems. We also build the corresponding models in LightTools, and the simulation results are in good agreement with experiment. In experiment, we achieved a 2.25x optical efficiency enhancement for both systems, which agrees with the simulation results (2.48x for Fresnel and 2.44x for "pancake" systems) well. Potential application for high efficiency VR displays is foreseeable.
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http://dx.doi.org/10.1364/OE.430920DOI Listing
June 2021

Artificial Intelligence System Application in Miliary Lung Metastasis: Experience from a Rare Case.

Risk Manag Healthc Policy 2021 5;14:2825-2829. Epub 2021 Jul 5.

Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

Introduction: Miliary intrapulmonary carcinomatosis (MIPC) is very rare in the existing literature. We reported a lung adenocarcinoma patient presented with over 200 uniform size pulmonary nodules in all lung lobes at the initial examination. The application of artificial intelligence (AI) in lung cancer has been gradually reported, but not yet reported in MIPC. The application of AI in this rare disease is worth exploring.

Patient Information: A 57-year-old woman received chest computed tomography (CT) scan because of dry cough, intermittent chest wall and back pain for 3 weeks. CT imaging found over 200 uniform size pulmonary nodules in an evenly dispersed pattern at bilateral lungs with a 38×45mm new creature at the dorsal segment of the lower lobe of the left lung. However, as a very reliable diagnostic assistant system in CT imaging of lung cancer, AI can only identify 18 nodules in such classic metastatic lung cancer case.

Conclusion: This case provides classical imaging figures as textbook-like, even though there is no such classic imaging of lung metastases in the existing textbooks. This medical imaging material will impress medical students and help them learn about the disease deeply. This medical imaging material can warn patients to recognize the horror of lung cancer metastasis and has good popularization of science. This medical imaging material presents a new challenge for AI.
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http://dx.doi.org/10.2147/RMHP.S315152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274706PMC
July 2021

Spatially Resolved Metabolomics and Lipidomics Reveal Salinity and Drought-Tolerant Mechanisms of Cottonseeds.

J Agric Food Chem 2021 Jul 12;69(28):8028-8037. Epub 2021 Jul 12.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR 999077, China.

In the current era of global climate change, environmental stresses, especially drought and salt, have impaired the growth and productivity of crops, e.g., cotton. Understanding the mechanisms of plants' adaptation to these abiotic stresses is crucial to breed stress-tolerant crop species. In the present study, integrated metabolomics, lipidomics, and mass spectrometry imaging (MSI) were used to discover the spatial distribution of differential metabolites and lipids in two cottonseed cultivars with contrasting drought and salt tolerance properties. Seventeen differential metabolites and 125 differential lipids were identified. Their possible roles in augmenting stress tolerance were illustrated, which were involved in reactive oxygen species scavenging, osmotic adjustment, and cell membrane structure reconstruction. MSI analysis provided a visualization of nine differential lipids and four differential metabolites in cottonseeds with varied abundances and distributions. The results may help understand cottonseeds' convictive metabolic and lipidomic regulatory networks in coping with salinity and drought stresses and give new insights into the stress-tolerance traits relevant to other crops.
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http://dx.doi.org/10.1021/acs.jafc.1c01598DOI Listing
July 2021

Combined QTL mapping and association study reveals candidate genes for leaf number and flowering time in maize.

Theor Appl Genet 2021 Jul 11. Epub 2021 Jul 11.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

Key Message: Twelve QTL for flowering and leaf number were detected. The ZmWRKY14 could increase leaf number, flowering time and biomass yield which are promising for silage maize breeding. Silage maize, one of the most important feedstock for ruminants, is widely grown from temperate regions to the tropics. Flowering time and leaf number are two significantly correlated traits and important for the quality, adaptation and biomass yield of silage maize. In this study, a recombinant inbred line population consisting of 215 individuals and an association panel of 369 inbred lines were analysed in field conditions in three locations for 2 consecutive years, and five, four and three quantitative trait loci for the total leaf number, days to anthesis (DTA) and silking (DTS) were detected, which could explain 48.55, 35.37 and 34.22% of total phenotypic variation, respectively. Association analysis of qLN10 on chromosome 10 found that ZmWRKY14 was the candidate gene for leaf number, whose expression level was negatively correlated with the leaf number. There are five haplotypes for ZmWRKY14, and haplotype 4 could significantly increase flowering time, leaf number and biomass yield, but has no obvious influence on ear weight. The optimal allelic combination of ZmWRKY14 and ZCN8 could further increase leaf number and biomass yield. The results will provide important genetic information for silage maize breeding.
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http://dx.doi.org/10.1007/s00122-021-03907-xDOI Listing
July 2021

YAP-Dependent Induction of CD47-Enriched Extracellular Vesicles Inhibits Dendritic Cell Activation and Ameliorates Hepatic Ischemia-Reperfusion Injury.

Oxid Med Cell Longev 2021 22;2021:6617345. Epub 2021 Jun 22.

Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatic ischemia-reperfusion injury (IRI) is the most common cause of liver damage leading to surgical failures in hepatectomy and liver transplantation. Extensive inflammatory reactions and oxidative responses are reported to be the major processes exacerbating IRI. The involvement of Yes-associated protein (YAP) in either process has been suggested, but the role and mechanism of YAP in IRI remain unclear. In this study, we constructed hepatocyte-specific YAP knockout (YAP-HKO) mice and induced a hepatic IRI model. Surprisingly, the amount of serum EVs decreased in YAP-HKO compared to WT mice during hepatic IRI. Then, we found that the activation of YAP increased EV secretion through F-actin by increasing membrane formation, while inhibiting the fusion of multivesicular body (MVB) and lysosomes in hepatocytes. Further, to explore the essential elements of YAP-induced EVs, we applied mass spectrometry and noticed CD47 was among the top targets highly expressed on hepatocyte-derived EVs. Thus, we enriched CD47 EVs by microbeads and applied the isolated CD47 EVs on IRI mice. We found ameliorated IRI symptoms after CD47 EV treatment in these mice, and CD47 EVs bound to CD172 on the surface of dendritic cells (DCs), which inhibited DC activation and the cascade of inflammatory responses. Our data showed that CD47-enriched EVs were released in a YAP-dependent manner by hepatocytes, which could inhibit DC activation and contribute to the amelioration of hepatic IRI. CD47 EVs could be a potential strategy for treating hepatic IRI.
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http://dx.doi.org/10.1155/2021/6617345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241504PMC
June 2021

Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine.

Sci Adv 2021 Jul 2;7(27). Epub 2021 Jul 2.

Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, GA 30602, USA.

Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing the SARS-CoV-2 S protein (CVXGA1), and then demonstrated that a single-dose intranasal immunization with CVXGA1 protects against lethal infection of K18-hACE2 mice, a severe disease model. CVXGA1 immunization also prevented virus infection of ferrets and blocked contact transmission. This mucosal vaccine strategy inhibited SARS-CoV-2 replication in the upper respiratory tract, thus preventing disease progression to the lower respiratory tract. A PIV5-based mucosal vaccine provides a strategy to induce protective innate and cellular immune responses and reduce SARS-CoV-2 infection and transmission in populations.
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http://dx.doi.org/10.1126/sciadv.abi5246DOI Listing
July 2021

Derivatization strategy for semi-quantitative analysis of medium- and long-chain fatty acids using multiple reaction monitoring.

Talanta 2021 Oct 15;233:122464. Epub 2021 May 15.

Department of Respirology & Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, 518020, China; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address:

Medium- and long-chain fatty acids (MLFAs) are essential energy sources in cells and possess vital biological functions. Characteristics of MLFAs in biosamples contributes to the understanding of biological process and finding potential biomarkers for relevant diseases. However, there are obstacles of the MLFAs determination due to their poor ionization efficiency in mass spectrometry and structural similarity of the MLFAs. Herein, a derivatization strategy was applied by labeling with d0-N, N-dimethyl-6,7-dihydro-5H-pyrrolo [3,4-d] pyrimidine-2-amine (d-DHPP) and detecting with ultra-high performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) in multiple reaction monitoring (MRM) mode. The parallel isotope labeled internal standards were generated by tagging d-DHPP to MLFAs. The simple and rapid derivatization procedure and mild reaction conditions greatly reduced the potential of MLFA degradation during the processing procedure. With the methodology, the chromatographic performance was greatly improved, and the mass spectrum response was enhanced up to 1, 600 folds. Finally, the developed derivatization method was applied to serum samples to analyze the alteration of MLFAs induced by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) exposure in breast cancer nude mice. The semi-quantitative results demonstrated that the BDE-47 exposure significantly influenced the MLFA metabolism in mice.
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http://dx.doi.org/10.1016/j.talanta.2021.122464DOI Listing
October 2021

Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis.

J Oncol 2021 5;2021:9951010. Epub 2021 Jun 5.

Medical Laboratory Center, Yantai Yuhuangding Hospital, Yantai 264000, China.

Background: Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC.

Materials And Methods: RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion.

Results: Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression.

Conclusions: WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.
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http://dx.doi.org/10.1155/2021/9951010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203383PMC
June 2021

Clinical application of enhanced recovery after surgery in lumbar disk herniation patients undergoing dynamic stabilization and discectomy.

J Back Musculoskelet Rehabil 2021 Jun 25. Epub 2021 Jun 25.

Background: Enhanced recovery after surgery (ERAS) has been demonstrated to improve early postoperative outcomes and is becoming a crucial component of any perioperative management paradigm.

Objective: To investigate the effect of an ERAS protocol on lumbar disk herniation (LDH) patients undergoing dynamic stabilization and discectomy.

Methods: A total of 119 lumbar disk herniation (LDH) patients undergoing Dynesys dynamic stabilization and discectomy were divided into the ERAS (n1 = 56) and control group (n2 = 63). ERAS group received an enhanced recovery after surgery (ERAS) protocol, and control group received a traditional care protocol.

Results: Both the ERAS and control groups had significantly decreased visual analog scale (VAS) score and Oswestry Disability Index (ODI) and increased Japanese Orthopaedic Association (JOA) score at postoperative 1 week, 1 month and 3 months compared with preoperative scores. Moreover, the ERAS group had lower postoperative VAS score and ODI and higher postoperative JOA score and rate of improved JOA score compared with the control group. Intraoperative blood loss, operation time, ambulation time and length of stay were all lower in the ERAS group than in the control group.

Conclusions: The ERAS protocol designed was feasible for LDH patients undergoing dynamic stabilization and discectomy with significantly improved perioperative outcomes.
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http://dx.doi.org/10.3233/BMR-200238DOI Listing
June 2021

[Robotic arm control system based on augmented reality brain-computer interface and computer vision].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Jun;38(3):483-491

Medical Equipment Management Division of 3201 Hospital, Hanzhong, Shaanxi 723000, P.R.China.

Brain-computer interface (BCI) has great potential to replace lost upper limb function. Thus, there has been great interest in the development of BCI-controlled robotic arm. However, few studies have attempted to use noninvasive electroencephalography (EEG)-based BCI to achieve high-level control of a robotic arm. In this paper, a high-level control architecture combining augmented reality (AR) BCI and computer vision was designed to control a robotic arm for performing a pick and place task. A steady-state visual evoked potential (SSVEP)-based BCI paradigm was adopted to realize the BCI system. Microsoft's HoloLens was used to build an AR environment and served as the visual stimulator for eliciting SSVEPs. The proposed AR-BCI was used to select the objects that need to be operated by the robotic arm. The computer vision was responsible for providing the location, color and shape information of the objects. According to the outputs of the AR-BCI and computer vision, the robotic arm could autonomously pick the object and place it to specific location. Online results of 11 healthy subjects showed that the average classification accuracy of the proposed system was 91.41%. These results verified the feasibility of combing AR, BCI and computer vision to control a robotic arm, and are expected to provide new ideas for innovative robotic arm control approaches.
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http://dx.doi.org/10.7507/1001-5515.202011039DOI Listing
June 2021

Cross-cultural and psychometric property assessment of the Moorong Self-Efficacy Scale in Chinese patients with spinal cord injury.

Disabil Rehabil 2021 Jun 24:1-7. Epub 2021 Jun 24.

School of Nursing, Sun Yat-sen University, Guangzhou, China.

Purpose: To translate the Moorong Self-Efficacy Scale (MSES) into Chinese and to examine its reliability and validity in patients with spinal cord injury (SCI).

Methods: A cross-sectional study design was employed. The MSES was translated into Chinese by forward- and back-translation and its psychometric properties were examined among 176 patients with SCI recruited from four rehabilitation centers in China using convenience sampling.

Results: In this study, all 176 patients were aged from 18 to 90 years old with an average of 39.51 ± 14.07. The content validity index of the scale was 0.99. Principal components analysis with varimax orthogonal rotation was used. Three factors were extracted accounting for 39.083%, 11.149%, and 8.391% of the total variance and labeled as general self-efficacy (eight items), social self-efficacy (five items), and self-management self-efficacy (three items). Confirmatory factor analysis showed acceptable fit compared with previous studies. Pearson's correlation coefficient between the total scores of the MSES and the General Self-Efficacy Scale was 0.660 ( < 0.001). Cronbach's coefficient was 0.892 for total items and 0.862, 0.817, and 0.739 for the three factors. The interclass correlation coefficients between the pretest and retest were 0.859 (0.733-0.925) for the total score.

Conclusions: The Chinese version of the MSES is reliable and valid, suggesting that it is suitable for evaluating self-efficacy of Chinese patients with SCI.Implications for rehabilitationThe satisfactory reliability and validity of the Chinese version of the Moorong Self-Efficacy Scale (MSES) confirmed its suitability as a tool to measure self-efficacy among Chinese patients with spinal cord injury (SCI).The Chinese version of the MSES could be used to reflect the important and specific aspects of self-efficacy in patients with SCI such as self-care, social interaction, and daily activities, and to help medical stuff giving more targeted intervention.
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http://dx.doi.org/10.1080/09638288.2021.1939445DOI Listing
June 2021

The therapeutic effects and mechanisms of Long Chai Fang on chronic hepatitis B.

Ann Transl Med 2021 May;9(10):865

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Background: Long Chai Fang (LCF) is a traditional Chinese medicine (TCM) formula for treating chronic hepatitis B (CHB) in clinical settings; however, its related mechanism remains unclear.

Methods: To address this issue, network pharmacology and an integrative method that combines dot-blot hybridization and metabolomics analysis were employed. Network pharmacology was performed to investigate the material basis and potential mechanisms of LCF against CHB. The effect of LCF on Duck hepatitis B virus (DHBV) replication was evaluated. The metabolomics analysis was conducted to identify potential biomarkers in duck serum.

Results: The network pharmacology approach revealed 133 potential active components, 897 drug targets, 979 disease targets, and 185 drug-disease targets, while the Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 165 pathways. LCF significantly inhibited DHBV-deoxyribonucleic acid replication on day 10 and day 3 after the cessation of treatment. Notably, the low-dose LCF group showed the best inhibitory effect. The obviously sustained anti-DHBV activity of LCF inhibited viral replication, and a rebound reaction was found. Phosphatidylcholine and phosphatidylethanolamine classes, which are mainly involved in liver cell repair and energy metabolism through phospholipid metabolic pathways, were identified by metabolomics analysis.

Conclusions: our results showed that the main active ingredients of LCF appear to be metacarpi, isorhamnetin, glypallichalcone, and phaseolinisoflavan. This study provides novel strategies for using a LCF formula against CHB in future research.
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http://dx.doi.org/10.21037/atm-21-1923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184409PMC
May 2021

Multicenter phase II study of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis.

Chin J Cancer Res 2021 Apr;33(2):243-255

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Objective: Breast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization. This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM.

Methods: This trial involved four centers in China and was conducted from September 2016 to March 2020. Patients received apatinib 500 mg/d [either alone or with endocrine therapy if hormone receptor-positive (HR+)] until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint.

Results: We evaluated 26 patients for efficacy. The median PFS (mPFS) and median overall survival (mOS) were 4.9 [range: 2.0-28.5; 95% confidence interval (95% CI): 2.1-8.3] months and 18 (range: 3-55; 95% CI: 12.9-23.1) months, respectively. The objective response rate (ORR) was 42.3% (11/26), and the disease-control rate was 76.9% (20/26). In the subgroup analysis, HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95% CI: 2.2-11.8) months 2.3 (95% CI: 1.2-3.4) months, respectively (P=0.001); and mPFS in patients without or with chest wall radiotherapy was 6.4 (95% CI: 1.6-19.5) months 3.0 (95% CI: 1.3-4.6) months, respectively (P=0.041). In the multivariate analysis, HR+ status was the only independent predictive factor for favorable PFS (P=0.014).

Conclusions: Apatinib was highly effective for BC patients with CWM, especially when combined with endocrine therapy. PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy. However, adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.02.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181870PMC
April 2021

Estimate the Trend of COVID-19 Outbreak in China: a Statistical and Inferential Analysis on Provincial-level Data.

Procedia Comput Sci 2021 12;187:512-517. Epub 2021 Jun 12.

Research Department, ZCE Futures & Derivatives Institute Co., LTD., 31 Longhuwaihuan Eest Road, Zhengzhou, 450000, China.

The ongoing COVID-19 epidemic spreads with strong transmission power in every part of China. Analyses of the trend is highly need when the Chinese government makes plans and policies on epidemic control. This paper provides an estimation process on the trend of COVID-19 outbreak using the provincial-level data of the confirmed cases. On the basis of the previous studies, we introduce an effective and practical method to compute accurate basic reproduction numbers ( ) in each province-level division of China. The statistical results show a non-stop downward trend of the in China, and confirm that China has made significant progress on the epidemic control by lowering the provincial from 10 or above to 3.21 or less. In the inferential analysis, we introduce an effective model for the trend forecasting. The inferential results imply that the nationwide epidemic risk will fall to a safe level by the end of April in China, which matches the actual situation. The results provide more accurate method and information about COVID-19.
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http://dx.doi.org/10.1016/j.procs.2021.04.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197403PMC
June 2021

Effect of pH dynamic control on ethanol-lactic type fermentation (ELTF) performance of glucose.

Environ Technol 2021 Jun 17:1-37. Epub 2021 Jun 17.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, PR China.

This study proposed a new ethanol-lactic type fermentation (ELTF) and explored the optimal control strategy. Using batch experiments, the effects of pH, temperature and organic loading (OL) on ELTF was investigated. The sum of ethanol and lactic acid yield was highest at whole-control pH value of 4.0, 35℃ temperature and OL of 33 gCOD/L. To improve ELTF, the dynamic pH control in the long term CSTR was adjusted at 4.0 (1-28 day), 5.0 (29-44 day) and 4.0 (46-62 day) successively. The high concentration of ethanol and lactic acid was 8190.5 mg/L at 16 day of pH 4.0. At pH of 5.0, the average acidogenesis rate and total concentration of fermentation products increased 111.0% and 128.0%, respectively. Organisms of and were the predominant bacteria in reactor. It can achieve the directional regulation of ELTF and provides parameter support for the application of two-phase anaerobic digestion.
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http://dx.doi.org/10.1080/09593330.2021.1942560DOI Listing
June 2021

Layer-Number-Dependent Effects of Graphene Oxide on the Pluripotency of Mouse Embryonic Stem Cells Through the Regulation of the Interaction Between the Extracellular Matrix and Integrins.

Int J Nanomedicine 2021 4;16:3819-3832. Epub 2021 Jun 4.

Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.

Introduction: Embryonic stem cells (ESCs) possess great application prospects in biological research and regenerative medicine, so it is important to obtain ESCs with excellent and stable cellular states during in vitro expansion. The feeder layer culture system with the addition of leukemia inhibitory factor (LIF) is currently applied in ESC cultures, but it has a series of disadvantages that could influence the culture efficiency and quality of the ESCs. With the development of nanotechnology, many studies have applied nanomaterials to optimize the stem cell culture system and regulate the fate of stem cells. In this study, we investigated the layer-number-dependent biofunction of graphene oxide (GO) on the pluripotency of ESCs from mice (mESCs).

Methods: Single-layer GO (SGO) and multi-layer GO (MGO) were characterized and their effects on the cytotoxicity and self-renewal of mESCs were detected in vitro. The differentiation potentials of mESCs were identified through the formation of embryoid bodies and teratomas. The regulatory mechanism of GO was verified by blocking the target receptors on the surface of mESCs using antibodies.

Results: Both SGO and MGO were biocompatible with mESCs, but only MGO effectively sustained their self-renewal and differentiation potential. In addition, GO influenced the cellular activities of mESCs by regulating the interactions between extracellular matrix proteins and integrins.

Conclusion: This work demonstrates the layer-number-dependent effects of GO on regulating the cell behavior of mESCs and reveals the extracellular regulatory mechanism of this process.
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http://dx.doi.org/10.2147/IJN.S301892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189697PMC
June 2021

Genetic basis of molecular mechanisms in β-lactam resistant gram-negative bacteria.

Microb Pathog 2021 Jun 10;158:105040. Epub 2021 Jun 10.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China. Electronic address:

Antibiotic-resistant bacteria are considered one of the major global threats to human and animal health. The most harmful among the resistant bacteria are β-lactamase producing Gram-negative species (β-lactamases). β-lactamases constitute a paradigm shift in the evolution of antibiotic resistance. Therefore, it is imperative to present a comprehensive review of the mechanisms responsible for developing antimicrobial resistance. Resistance due to β-lactamases develops through a variety of mechanisms, and the number of resistant genes are involved that can be transferred between bacteria, mostly via plasmids. Over time, these new molecular-based resistance mechanisms have been progressively disclosed. The present review article provides information on the recent findings regarding the molecular mechanisms of resistance to β-lactams in Gram-negative bacteria, including CTX-M-type ESBLs with methylase activity, plasmids harbouring phages with β-lactam resistance genes, the co-presence of β-lactam resistant genes of unique combinations and the presence of β-lactam and non-β-lactam antibiotic-resistant genes in the same bacteria. Keeping in view, the molecular level resistance development, multifactorial and coordinated measures may be taken to counter the challenge of rapidly increasing β-lactam resistance.
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http://dx.doi.org/10.1016/j.micpath.2021.105040DOI Listing
June 2021

miR-340 Promotes Retinoblastoma Cell Proliferation, Migration and Invasion Through Targeting WIF1.

Onco Targets Ther 2021 4;14:3635-3648. Epub 2021 Jun 4.

Department of Pediatric Ophthalmology, Cangzhou Central Hospital, Cangzhou, 061001, People's Republic of China.

Background: MicroRNAs (miRNAs) function as important regulators of gene expression involved in tumor pathogenesis, including retinoblastoma. However, the expression profiles and potential roles in retinoblastoma are still largely unclear.

Material And Methods: Differentially expressed miRNAs (DEmiRs) and genes (DEGs) in retinoblastoma were extracted from Gene Expression Omnibus (GEO) repository. Expression levels of miR-340 and WIF1 were detected in retinoblastoma tissues and cell lines by qRT-PCR. Both gain-of-function and loss-of-function experiments were performed to explore the effects of miR-340 on cell proliferation, migration and invasion. Bioinformatics analysis and luciferase reporter assay were used to explore the interaction between miR-340 and WIF1.

Results: A total of 11 DEmiRs were identified in retinoblastoma tissue and blood samples. Among them, we validated that miR-340 was the most highly expressed miRNA and correlated with tumor size, ICRB stage and optic nerve invasion. miR-340 was observed to enhance the proliferation, migration and invasion capacity of retinoblastoma cells. We then identified 26 DEGs from 3 retinoblastoma GEO datasets and subsequently constructed a miRNA-mRNA regulatory network. Further analysis revealed that WIF1 was a direct target of miR-340. Moreover, overexpression of WIF1 could repress retinoblastoma progression induced by miR-340 in vitro and in vivo.

Conclusion: Collectively, miR-340 functioned as an oncomiRNA to promote retinoblastoma cell proliferation, migration and invasion via regulating WIF1. Our data also provided multiple miRNAs and genes that may contribute to a better understanding of retinoblastoma pathogenesis.
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http://dx.doi.org/10.2147/OTT.S302800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187089PMC
June 2021

Trifunctional Graphene Quantum [email protected] Integrated Nanoprobes for Visualization Therapy of Gastric Cancer.

Adv Healthc Mater 2021 Jun 10:e2100512. Epub 2021 Jun 10.

Research Center for Translational Medicine at East Hospital, Tongji University School of Life Science and Technology, Shanghai, 200092, China.

Visualization technology has become a trend in tumor therapy in recent years. The superior optical properties of graphene quantum dots (GQDs) make them suitable candidates for tumor diagnosis, but their tumor targeting and drug-carrying capacities are still not ideal for treatment. Sulfur-doped graphene quantum dots (SGQDs) with stable fluorescence are prepared in a previous study. A reliable strategy by associating layered double hydroxides (LDHs) and etoposide (VP16) is designed for precise visualization therapy. Trifunctional [email protected] integrated nanoprobes can simultaneously achieve targeted aggregation, fluorescence visualization, and chemotherapy. [email protected] can accumulate in the tumor microenvironment, owing to pH-sensitive properties and long-term photostability in vivo, which can provide a basis for cancer targeting, real-time imaging, and effect tracking. The enhanced therapeutic and attenuated side effects of VP16 are demonstrated, and the apoptosis caused by [email protected] is ≈2.7 times higher than that of VP16 alone, in HGC-27 cells. This work provides a theoretical and experimental basis for [email protected] as a potential multifunctional agent for visualization therapy of gastric cancer.
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http://dx.doi.org/10.1002/adhm.202100512DOI Listing
June 2021

Perceptions of patients with chronic obstructive pulmonary disease towards telemedicine: A qualitative systematic review.

Heart Lung 2021 Jun 6;50(5):675-684. Epub 2021 Jun 6.

School of Nursing, Jilin University, China.

Background: There are some qualitative studies on the views of patients with chronic obstructive pulmonary disease (COPD) on telemedicine, however, there are few related qualitative systematic reviews.

Objectives: To systematically review and synthesize qualitative studies involving the perceptions of patients with COPD about telemedicine to understand patients' attitudes and expectations for telemedicine and determine the obstacles and stimulus in the use of telemedicine.

Methods: We searched PubMed, Web of Science, MEDLINE, Embase and CINAHL for articles published from January 2000 to December 2020. The data were analysed using thematic synthesis.

Results: We included 20 articles involving 19 studies and 301 patients, and we identified four themes: perceived ease of use, perceived usefulness, perceived difficulty of use, and perceived uselessness. We found that although patients have different views on telemedicine, most of them have a positive attitude towards it.

Conclusions: The synthesis of views will help us determine the factors that promote or hinder the application of telemedicine and guide the design and implementation of telemedicine in the future.
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http://dx.doi.org/10.1016/j.hrtlng.2021.03.081DOI Listing
June 2021

Noninvasive discrimination of benign and malignant breast lesions using genome-wide nucleosome profiles of plasma cell-free DNA.

Clin Chim Acta 2021 Sep 6;520:95-100. Epub 2021 Jun 6.

Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China. Electronic address:

Background: Breast malignancy is the most frequently diagnosed malignancy in women worldwide, and the diagnosis relies on invasive examinations. However, most clinical breast changes in women are benign, and invasive diagnostic approaches cause unnecessary suffering for the patients. Thus, a novel noninvasive approach for discriminating malignant breast lesions from benign lesions is needed.

Methods: We performed cell-free DNA (cfDNA) sequencing on plasma samples from 173 malignant breast lesion patients, 158 benign breast lesion patients, and 102 healthy women. We then analyzed the cfDNA-based nucleosome profiles, which reflect the various tissues of origin and transcription factor activities. Moreover, by using machine learning classifiers along with the cfDNA sequencing data, we built classifiers for discriminating benign from malignant breast lesions. Receiver operating characteristic curve analyses were used to evaluate the performance of the classifiers.

Results: cfDNA-based nucleosome profiles reflected the various tissues of origin and transcription factor activities in benign and malignant breast lesions. The cfDNA-based transcription factor activities and breast malignancy-specific transcription factor-binding site accessibility profiles could accurately distinguish benign and malignant breast lesions, with area under the curve values of 0.777 and 0.824, respectively.

Conclusions: Our proof-of-principle study established a methodology for noninvasively discriminating benign from malignant breast lesions.
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http://dx.doi.org/10.1016/j.cca.2021.06.008DOI Listing
September 2021

Electron-Deficient-Type Electride CaPb: Extension of Electride Chemical Space.

J Am Chem Soc 2021 Jun 7;143(23):8821-8828. Epub 2021 Jun 7.

Materials Research Center for Element Strategy, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.

Electrides have been identified so far by two major routes: one is conversion of elemental metals and stoichiometric compounds by high pressure; the other is to search for electron-rich compounds, and this approach is more general. In contrast, few electron-deficient structures in existing databases have been revealed as potential electride candidates. In this work, we found an electron-deficient compound CaPb could be transformed into electrides upon applying external pressure or strain along the -axis, which induces the electron immigration from Pb to interstitial sites. Furthermore, the electron doping via Hf substitution of Ca atoms for CaPb was found to be capable of tuning the interstitial electron density under ambient pressure, resulting in a new stable ternary electride CaHfPb, Hf-substituted CaPb. The electron-deficient electride discovered here is of novel type and can largely expand the research scope of electrides. Considering a recently reported neutral electride NaN and the present finding, it is now clarified that electrides can be identified irrespective of stoichiometry (electron-rich, -neutral, or -poor) for compounds.
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http://dx.doi.org/10.1021/jacs.1c03278DOI Listing
June 2021

High-Pressure Phase Diagram of the Ti-O System.

J Phys Chem Lett 2021 Jun 4;12(23):5486-5493. Epub 2021 Jun 4.

Skolkovo Institute of Science and Technology, 3 Nobel Street, Moscow 143026, Russia.

Titanium oxides are technologically important compounds. The chemistry of the Ti-O system is quite rich, largely because of the multiple oxidation states that titanium atoms can take. In this work, using a combination of variable-composition evolutionary crystal structure prediction (USPEX code) and data mining (Materials Project), we predicted all of the stable titanium oxides in the pressure range 0-200 GPa and found that 27 compounds can be stable at different pressures. We resolved contradictions between previous works and predicted four hitherto-unknown stable phases: 2/-TiO, 4/-TiO, 2-TiO, and 3̅-TiO. We also showed that the high-pressure 6̅2-TiO phase is an electride.
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http://dx.doi.org/10.1021/acs.jpclett.1c01133DOI Listing
June 2021

Prediction of clinical prognosis in cutaneous melanoma using an immune-related gene pair signature.

Bioengineered 2021 12;12(1):1803-1812

Department of Orthopedics, Clinical Medical College, Guizhou Medical University, Guiyang, China.

Cutaneous melanoma (CM) is a malignant and aggressive skin cancer that is the leading cause of skin cancer-related deaths. Increasing evidence shows that immunity plays a vital role in the prognosis of CM. In this study, we developed an immune-related gene pair (IRGP) signature to predict the clinical prognosis of patients with CM. Immune-related genes from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were selected to construct the IRGPs, and patients with CM in these two cohorts were assigned to low- and high-risk subgroups. Moreover, we investigated the IRGPs and their individualized prognostic signatures using Kaplan-Meier survival analysis, univariate and multivariate Cox analyses, and analysis of immune cell infiltration in CM. A 41-IRGP signature was constructed from 2498 immune genes that could significantly predict the overall survival of patients with CM in both the TCGA and GEO cohorts. Immune infiltration analysis indicated that several immune cells, especially M1 macrophages and activated CD4 T cells, were significantly associated with the prognostic effect of the IRGP signature in patients with CM. Overall, the IRGP signature constructed in this study was useful for determining the prognosis of patients with CM and for providing further understanding of CM immunotherapy.
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http://dx.doi.org/10.1080/21655979.2021.1924556DOI Listing
December 2021

One Health: An inclusive framework to curb the COVID-19 pandemic.

EXCLI J 2021 26;20:724-726. Epub 2021 Mar 26.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China.

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http://dx.doi.org/10.17179/excli2021-3615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144536PMC
March 2021

Therapeutic effect of various ginsenosides on rheumatoid arthritis.

BMC Complement Med Ther 2021 May 25;21(1):149. Epub 2021 May 25.

Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, China.

Background: Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug.

Methods: The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides.

Results: All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6.

Conclusion: Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.
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http://dx.doi.org/10.1186/s12906-021-03302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145820PMC
May 2021

Image-Guided Human Reconstruction via Multi-Scale Graph Transformation Networks.

IEEE Trans Image Process 2021 25;30:5239-5251. Epub 2021 May 25.

3D human reconstruction from a single image is a challenging problem. Existing methods have difficulties to infer 3D clothed human models with consistent topologies for various poses. In this paper, we propose an efficient and effective method using a hierarchical graph transformation network. To deal with large deformations and avoid distorted geometries, rather than using Euclidean coordinates directly, 3D human shapes are represented by a vertex-based deformation representation that effectively encodes the deformation and copes well with large deformations. To infer a 3D human mesh consistent with the input real image, we also use a perspective projection layer to incorporate perceptual image features into the deformation representation. Our model is easy to train and fast to converge with short test time. Besides, we present the DHuman (Dynamic Detailed Human) dataset, including variously posed 3D human meshes with consistent topologies and rich geometry details, together with the captured color images and SMPL models, which is useful for training and evaluation of deep frameworks, particularly for graph neural networks. Experimental results demonstrate that our method achieves more plausible and complete 3D human reconstruction from a single image, compared with several state-of-the-art methods. The code and dataset are available for research purposes at http://cic.tju.edu.cn/faculty/likun/projects/MGTnet.
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http://dx.doi.org/10.1109/TIP.2021.3080177DOI Listing
May 2021