Publications by authors named "Yixin Wang"

221 Publications

Oral probiotics vaccine expressing koi herpesvirus (KHV) ORF81 protein delivered by chitosan-alginate capsules is a promising strategy for mass oral vaccination of carps against KHV infection.

J Virol 2021 Apr 7. Epub 2021 Apr 7.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin, P.R. China

Koi herpesvirus (KHV) is highly contagious and lethal to cyprinid fish, causing significant economic losses to the carp aquaculture industry, particularly to koi carp breeders. Vaccines delivered through intramuscular needle injection or gene gun are not suitable for mass vaccination of carp. So, the development of cost-effective, oral vaccines that are easily applicable at farm level is highly desirable. In this study, we utilized chitosan-alginate capsules as oral delivery system for a live probiotic () vaccine pYG-KHV-ORF81/LR CIQ249 expressing KHV ORF81 protein. The tolerance of the encapsulated recombinant to various digestive environments and the ability of the probiotics strain to colonize the intestine of carp was tested. The immunogenicity and the protective efficacy of the encapsulated probiotic vaccine was evaluated by determining IgM levels, lymphocyte proliferation, expression of immune-related genes, and viral challenge to vaccinated fish. It was clear that the chitosan-alginate capsules protected the probiotics vaccine effectively against extreme digestive environments, and significant level ( < 0.01) of antigen-specific IgM with KHV-neutralizing activity was detected, which provided protection rate of ca. 85% for koi carp against KHV challenge. The strategy of using chitosan-alginate capsules to deliver probiotic vaccines is easily applicable for mass oral vaccination of fish.An oral probiotic vaccine pYG-KHV-ORF81/LR CIQ249 encapsulated by chitosan-alginate capsules as oral delivery system was developed for koi carp against KHV infection. This encapsulated probiotic vaccine can be protected from various digestive environments and maintain effectively high viability, showing a good tolerance to digestive environments. This encapsulated probiotic vaccine has a good immunogenicity in koi carp via oral vaccination, and the significant level of antigen-specific IgM was effectively induced after oral vaccination, displaying effective KHV-neutralizing activity. This encapsulated probiotic vaccine can provide effective protection for koi carp against KHV challenge, which is handling stress-free for the fish, cost-effective, and suitable for the mass oral vaccination of koi carp at farm level, suggesting a promising vaccine strategy for fish.
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http://dx.doi.org/10.1128/JVI.00415-21DOI Listing
April 2021

Biogenetic Acellular Dermal Matrix Maintaining Rich Interconnected Microchannels for Accelerated Tissue Amendment.

ACS Appl Mater Interfaces 2021 Apr 5. Epub 2021 Apr 5.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Given that many people suffer from extensive skin damage, wound repair has drawn tremendous attention in research. Among the various assistant dressing materials that promote healing, a porcine acellular dermal matrix (PADM), as a skin substitute, can efficiently accelerate healing by promoting cell migration and proliferation. However, a simple, low-cost preparation process remains a challenge facing PADM development, particularly because of the inferior elasticity. To overcome these drawbacks, a CaCl-ethanol-HO solution (ternary solution) combined with an additional enzyme treatment was used to obtain a transparent, porous, and elastic PADM that retained the major extracellular matrix composition of the dermis. Our results indicated that alterations in the fiber organization and secondary structural changes in the collagen occurred after treatment. Furthermore, the wound healing and histological analyses clearly revealed an extremely expedited wound repair process following the application of the biocompatible PADM. In conclusion, this study provides new insights into the development of a transparent PADM with a porous structure and good elasticity that can be used as a skin substitute to accelerate the wound healing process. Moreover, this effective technique could potentially be used to extrapolate other decellularized materials in the future.
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http://dx.doi.org/10.1021/acsami.1c00420DOI Listing
April 2021

Biogenetic Acellular Dermal Matrix Maintaining Rich Interconnected Microchannels for Accelerated Tissue Amendment.

ACS Appl Mater Interfaces 2021 Apr 5. Epub 2021 Apr 5.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Given that many people suffer from extensive skin damage, wound repair has drawn tremendous attention in research. Among the various assistant dressing materials that promote healing, a porcine acellular dermal matrix (PADM), as a skin substitute, can efficiently accelerate healing by promoting cell migration and proliferation. However, a simple, low-cost preparation process remains a challenge facing PADM development, particularly because of the inferior elasticity. To overcome these drawbacks, a CaCl-ethanol-HO solution (ternary solution) combined with an additional enzyme treatment was used to obtain a transparent, porous, and elastic PADM that retained the major extracellular matrix composition of the dermis. Our results indicated that alterations in the fiber organization and secondary structural changes in the collagen occurred after treatment. Furthermore, the wound healing and histological analyses clearly revealed an extremely expedited wound repair process following the application of the biocompatible PADM. In conclusion, this study provides new insights into the development of a transparent PADM with a porous structure and good elasticity that can be used as a skin substitute to accelerate the wound healing process. Moreover, this effective technique could potentially be used to extrapolate other decellularized materials in the future.
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http://dx.doi.org/10.1021/acsami.1c00420DOI Listing
April 2021

Does non-COVID-19 lung lesion help? investigating transferability in COVID-19 CT image segmentation.

Comput Methods Programs Biomed 2021 Apr 23;202:106004. Epub 2021 Feb 23.

Institute of Computing Technology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China; Lenovo Corporate Research & Development, Lenovo Ltd., Beijing, China. Electronic address:

Background And Objective: Coronavirus disease 2019 (COVID-19) is a highly contagious virus spreading all around the world. Deep learning has been adopted as an effective technique to aid COVID-19 detection and segmentation from computed tomography (CT) images. The major challenge lies in the inadequate public COVID-19 datasets. Recently, transfer learning has become a widely used technique that leverages the knowledge gained while solving one problem and applying it to a different but related problem. However, it remains unclear whether various non-COVID19 lung lesions could contribute to segmenting COVID-19 infection areas and how to better conduct this transfer procedure. This paper provides a way to understand the transferability of non-COVID19 lung lesions and a better strategy to train a robust deep learning model for COVID-19 infection segmentation.

Methods: Based on a publicly available COVID-19 CT dataset and three public non-COVID19 datasets, we evaluate four transfer learning methods using 3D U-Net as a standard encoder-decoder method. i) We introduce the multi-task learning method to get a multi-lesion pre-trained model for COVID-19 infection. ii) We propose and compare four transfer learning strategies with various performance gains and training time costs. Our proposed Hybrid-encoder Learning strategy introduces a Dedicated-encoder and an Adapted-encoder to extract COVID-19 infection features and general lung lesion features, respectively. An attention-based Selective Fusion unit is designed for dynamic feature selection and aggregation.

Results: Experiments show that trained with limited data, proposed Hybrid-encoder strategy based on multi-lesion pre-trained model achieves a mean DSC, NSD, Sensitivity, F1-score, Accuracy and MCC of 0.704, 0.735, 0.682, 0.707, 0.994 and 0.716, respectively, with better genetalization and lower over-fitting risks for segmenting COVID-19 infection.

Conclusions: The results reveal the benefits of transferring knowledge from non-COVID19 lung lesions, and learning from multiple lung lesion datasets can extract more general features, leading to accurate and robust pre-trained models. We further show the capability of the encoder to learn feature representations of lung lesions, which improves segmentation accuracy and facilitates training convergence. In addition, our proposed Hybrid-encoder learning method incorporates transferred lung lesion features from non-COVID19 datasets effectively and achieves significant improvement. These findings promote new insights into transfer learning for COVID-19 CT image segmentation, which can also be further generalized to other medical tasks.
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http://dx.doi.org/10.1016/j.cmpb.2021.106004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899930PMC
April 2021

CO -Strengthened Double-Cross-Linked Polymer Gels from Frustrated Lewis Pair Networks.

Macromol Rapid Commun 2021 Mar 24;42(6):e2000699. Epub 2021 Feb 24.

State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.

Conventional thermosets consisting of polymer networks with robust and irreversible chemical linkages are incapable of reshaping or reprocessing once formed. In contrast, reversible non-covalent crosslinks can impart structurally flexible and reconfigurable feature to the networks, but at the expense of certain mechanical strength. The integration of fixed covalent bonds and noncovalent bonds into these materials can usually attain enhanced mechanical properties and meanwhile provide dynamic and adaptable functions, such as responsive and healing ability to external stimuli. Here a double-cross-linked frustrated Lewis pair network (FLPN) is developed through a specific three-component reaction among triarylborane, triarylphosphine, and CO , which is composed of permanent chemical crosslinks and dynamic CO gas-bridged connections. The amount of CO added can regulate the density of supramolecular node in such FLPN, so as to control the strength and toughness of the gel material. Moreover, the broken gel can be rapidly healed by CO stimulus through the reconstruction of dynamic covalent network. This study will inspire a new way to create gas-based smart materials by incorporating frustrated Lewis pair chemistry into traditional gel system.
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http://dx.doi.org/10.1002/marc.202000699DOI Listing
March 2021

Diastolic dysfunction and impaired cardiac output reserve in dysmetabolic nonhuman primate with proteinuria.

J Diabetes Complications 2021 Apr 5;35(4):107881. Epub 2021 Feb 5.

Crown Bioscience Inc., 6 West Beijing Road, Taicang, Jiangsu, China. Electronic address:

Background: Cardiorenal complications are common in patients with dysmetabolism and diabetes. The present study aimed to examine if a nonhuman primate (NHP) model with spontaneously developed metabolic disorder and diabetes develops similar complications to humans, such as proteinuria and cardiac dysfunction at resting condition or diminished cardiac functional reserve following dobutamine stress echocardiography (DSE).

Methods And Results: A total of 66 dysmetabolic and diabetic cynomolgus (Macaca fascicularis) NHPs were enrolled to select 19 NHPs (MetS) with marked metabolic disorders and diabetes (fasting blood glucose: 178 ± 18 vs. 61 ± 3 mg/dL) accompanied by proteinuria (ACR: 134 ± 34 vs. 1.5 ± 0.4 mg/mmol) compared to 8 normal NHPs (CTRL). Under resting condition, MetS NHPs showed mild left ventricular (LV) diastolic dysfunction (E/A: 1 ± 0.06 vs. 1.5 ± 0.13), but with preserved ejection fraction (EF: 65 ± 2 vs. 71 ± 3%) compared to CTRL. DSE with an intravenous infusion of dobutamine at ascending doses (5, 10, 20, 30 and 40 μg/kg/min, 7 min for each dose) resulted in a dose-dependent increase in cardiac function, however, with a significantly diminished magnitude at the highest dose of dobutamine infusion (40 μg/kg/min) in both diastole (E/A: -12 ± 3 vs. -38 ± 5%) and systole (EF: 25 ± 3 vs. 33 ± 5%) as well as ~42% reduced cardiac output reserve (COR: 63 ± 8 vs. 105 ± 18%, p < 0.02) in the MetS compared to CTRL NHPs.

Conclusion: These data demonstrate that MetS NHPs with cardiorenal complications: proteinuria, LV diastolic dysfunction and preserved LV systolic function under resting conditions displayed compromised cardiac functional reserve under dobutamine stress. Based on these phenotypes, this NHP model of diabetes with cardiorenal complications can be used as a highly translational model mimic human disease for pharmaceutical research.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107881DOI Listing
April 2021

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.

Nat Commun 2021 01 8;12(1):134. Epub 2021 Jan 8.

State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.
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http://dx.doi.org/10.1038/s41467-020-20457-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794309PMC
January 2021

Advance directives and end-of-life care: knowledge and preferences of patients with brain Tumours from Anhui, China.

BMC Cancer 2021 Jan 5;21(1):25. Epub 2021 Jan 5.

Department of Oncology, Hefei Cancer Hospital; Chinese Academy of Sciences, Hefei, 230031, Anhui, China.

Background: In Mainland China, advance directives (ADs) and end-of-life care for patients with tumours, especially patients with brain tumours who may have lost consciousness or the ability to speak at the early stage of their illness, have been poorly acknowledged. Thus, this study aimed to clarify the knowledge and preferences of ADs and end-of-life care in patients with brain tumours and to investigate predictors of patient preferences.

Methods: This was a population-based cross-sectional survey that was conducted via face-to-face interviews. Information on sociodemographic factors, brain tumour illness, knowledge and preferences of the advanced decisions and end-of-life care of the patients was collected.

Results: A total of 88.61% of participants had never heard of ADs, but 65.18% reported that they would like to make ADs. Knowledge of ADs, receiving surgical treatment or radiotherapy, being younger than 70 years old, being male, having educational qualifications of college or beyond, being childless, having medical insurance for nonworking or working urban residents and self-paying medical expenses were predictors of preference for making ADs. A total of 79.43% of participants wanted to discuss end-of-life arrangements with medical staff, and 63.29% of participants were willing to receive end-of-life care, even though it would not delay death. A total of 65.82% of patients with brain tumours wanted resuscitation, and as many as 45.45% of the patients thought that they did not need life support if they were in a persistent vegetative state. Brain primary tumours, being younger than 70 years old, male sex, educational qualification of junior middle school or below, having children, having new rural cooperative medical insurance and having medical expenses paid by children or spouses were predictors of choosing appropriate palliative care.

Conclusions: ADs and end-of-life care have been poorly acknowledged among patients with brain tumours in mainland China. Additional efforts should be encouraged amongst patients with primary brain tumours, those who are undergoing surgery and radiotherapy and those who have low socioeconomic status. A longitudinal and comprehensive study is encouraged to promote disease-specific ADs among Chinese patients with brain tumours.
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http://dx.doi.org/10.1186/s12885-020-07775-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786498PMC
January 2021

Toward data-efficient learning: A benchmark for COVID-19 CT lung and infection segmentation.

Med Phys 2021 Mar 6;48(3):1197-1210. Epub 2021 Feb 6.

Department of Mathematics, Nanjing University, Nanjing, 210093, P. R. China.

Purpose: Accurate segmentation of lung and infection in COVID-19 computed tomography (CT) scans plays an important role in the quantitative management of patients. Most of the existing studies are based on large and private annotated datasets that are impractical to obtain from a single institution, especially when radiologists are busy fighting the coronavirus disease. Furthermore, it is hard to compare current COVID-19 CT segmentation methods as they are developed on different datasets, trained in different settings, and evaluated with different metrics.

Methods: To promote the development of data-efficient deep learning methods, in this paper, we built three benchmarks for lung and infection segmentation based on 70 annotated COVID-19 cases, which contain current active research areas, for example, few-shot learning, domain generalization, and knowledge transfer. For a fair comparison among different segmentation methods, we also provide standard training, validation and testing splits, evaluation metrics and, the corresponding code.

Results: Based on the state-of-the-art network, we provide more than 40 pretrained baseline models, which not only serve as out-of-the-box segmentation tools but also save computational time for researchers who are interested in COVID-19 lung and infection segmentation. We achieve average dice similarity coefficient (DSC) scores of 97.3%, 97.7%, and 67.3% and average normalized surface dice (NSD) scores of 90.6%, 91.4%, and 70.0% for left lung, right lung, and infection, respectively.

Conclusions: To the best of our knowledge, this work presents the first data-efficient learning benchmark for medical image segmentation, and the largest number of pretrained models up to now. All these resources are publicly available, and our work lays the foundation for promoting the development of deep learning methods for efficient COVID-19 CT segmentation with limited data.
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http://dx.doi.org/10.1002/mp.14676DOI Listing
March 2021

Changes of the flavor substances and protein degradation of black carp (Mylopharyngodon piceus) pickled products during steaming.

J Sci Food Agric 2020 Dec 21. Epub 2020 Dec 21.

Shanghai Engineering Research Center of Aquatic Product Processing and Preservation, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.

Background: Among various cooking methods, steaming is favored by many because it can cause less damage to nutrient components in muscle, retain the inherent food flavor, and reduce the generation of harmful substances. Steaming conditions are closely related to fish flavor, fat and protein oxidation, and digestibility.

Results: The black carp steamed for 4 to 14 min was studied in this article based on sensory assessment, electronic tongue, free amino acids, adenosine triphosphate (ATP)-related compounds, total nitrogen and non-protein nitrogen to explore the effect of steaming time on the taste substances and protein degradation of pickled black carp. The experimental result showed that the meat steamed within 8 min tasted better, showing high tastiness. The sensory assessment score increased significantly to the maximum value of 82.33 at 6 min. The content of umami and sweet amino acids increased significantly to the maximum value of 1.6801 g kg at 6 min. In the meantime, the IMP (inosine monophosphate) content was 1.9128 g kg , with its taste activity value (TAV) reaching 7.65, which proved that IMP affected the taste most. Furthermore, the total nitrogen content was 30.77 g kg , which meant protein degraded a great deal. Based on equivalent umami concentration (EUC) and its TAV, the meat tasted best at 6-8 min. The longer the steaming time, the faster the protein degradation and the more the flavor precursors.

Conclusion: The black carp pickled products (with a weight of 20 g, with the size of 3 cm × 3 cm × 2 cm) is suggested to be steamed for 6 to 8 min. This conclusion provides a theoretical basis for its better taste quality. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11038DOI Listing
December 2020

Sec-Eliminating the SARS-CoV-2 by AlGaN Based High Power Deep Ultraviolet Light Source.

Adv Funct Mater 2020 Nov 25:2008452. Epub 2020 Nov 25.

State Key Laboratory of Artificial Microstructure and Mesoscopic Physics School of Physics, Nano-Optoelectronics Frontier Center of Ministry of Education (NFC-MOE) Peking University Beijing 100871 China.

The world-wide spreading of coronavirus disease (COVID-19) has greatly shaken human society, thus effective and fast-speed methods of non-daily-life-disturbance sterilization have become extremely significant. In this work, by fully benefitting from high-quality AlN template (with threading dislocation density as low as ≈6×10 cm) as well as outstanding deep ultraviolet (UVC-less than 280 nm) light-emitting diodes (LEDs) structure design and epitaxy optimization, high power UVC LEDs and ultra-high-power sterilization irradiation source are achieved. Moreover, for the first time, a result in which a fast and complete elimination of SARS-CoV-2 (the virus causes COVID-19) within only 1 s is achieved by the nearly whole industry-chain-covered product. These results advance the promising potential in UVC-LED disinfection particularly in the shadow of COVID-19.
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http://dx.doi.org/10.1002/adfm.202008452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744859PMC
November 2020

The APETALA2 transcription factor LsAP2 regulates seed shape in lettuce.

J Exp Bot 2021 Mar;72(7):2463-2476

Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, Department of Vegetable Science, College of Horticulture, China Agricultural University, Beijing, China.

Seeds are major vehicles of propagation and dispersal in plants. A number of transcription factors, including APETALA2 (AP2), play crucial roles during the seed development process in various plant species. However, genes essential for seed development and the regulatory networks that operate during seed development remain unclear in lettuce. Here, we identified a lettuce AP2 (LsAP2) gene that was highly expressed during the early stages of seed development. LsAP2 knockout plants obtained by the CRISPR/Cas9 system were used to explore the biological function of LsAP2. Compared with the wild type, the seeds of Lsap2 mutant plants were longer and narrower, and developed an extended tip at the seed top. After further investigating the structural characteristics of the seeds of Lsap2 mutant plants, we proposed a new function of LsAP2 in seed dispersal. Moreover, we identified several interactors of LsAP2. Our results showed that LsAP2 directly interacted with the lettuce homolog of BREVIPEDICELLUS (LsBP) and promoted the expression of LsBP. Transcriptome analysis revealed that LsAP2 might also be involved in brassinosteroid biosynthesis and signaling pathways. Taken together, our data indicate that LsAP2 has a significant function in regulating seed shape in lettuce.
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http://dx.doi.org/10.1093/jxb/eraa592DOI Listing
March 2021

A prospective study of waist circumference trajectories and incident cardiovascular disease in China: the Kailuan Cohort Study.

Am J Clin Nutr 2021 02;113(2):338-347

Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA.

Background: Single measurements of waist circumference (WC) predict the incident cardiovascular disease (CVD); however, long-term patterns of WC and their association with the incidence of CVD are poorly characterized.

Objective: We aimed to identify WC trajectories and determine their association with incident CVD (stroke and myocardial infarction) and examine whether the association persisted among individuals without obesity.

Methods: We included 75,535 participants from a community-based cohort in China who were aged >18 y and free of stroke, coronary artery disease, and cancer in 2010 (the baseline). WC and other covariates were repeatedly measured in 2006, 2008, and 2010. WC trajectories were identified by latent mixture modeling. A Cox proportional hazards model was used to examine the association between WC trajectories and incident CVD, after adjustment for age, sex, income, education, systolic blood pressure, lipid profiles, plasma concentrations of glucose, C-reactive protein, smoking, and alcohol drinking.

Results: We identified 4 WC trajectories based on 2006 WC measurement and change patterns during 2006-2010: low stable (n = 12,072; mean WC 74.1-75.1 cm), moderate stable (n = 41,750; mean WC 85.1-86.6 cm), moderate-high stable (n = 19,914; mean WC 95.6-97.2 cm), and high stable (n = 1,799; mean WC 106.3-110.9 cm). During 2010-2016, we documented 2819 incident CVD events. Compared with the low-stable group, groups with elevated WC trajectories had a higher risk of CVD events during 6 y of follow-up (2010-2016). Adjusted HRs (95% CIs) were 1.49 (1.21, 1.83) for the moderate stable group, 1.71(1.38, 2.12) for the moderate-high stable group, and 1.45 (1.06, 2.00) for the high stable group. After further adjusting for BMI or excluding obese participants, we observed similar results. The positive association between WC and incident CVD was higher in individuals who were aged <60 y (P-interaction < 0.0001).

Conclusions: WC trajectory patterns were associated with altered risk of CVD among Chinese adults, even among people without BMI-defined obesity. When stratifying by age, the association was observed to be higher in younger adults.
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http://dx.doi.org/10.1093/ajcn/nqaa331DOI Listing
February 2021

Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot.

Proc Natl Acad Sci U S A 2020 12 14;117(52):32962-32969. Epub 2020 Dec 14.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China

Clinical investigations have shown that a nonimmunogenic "cold" tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor "hot." Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Meanwhile, ROS will induce potent immunogenic cell death (ICD) and further promote the accumulation of dendritic cells (DCs) and T cells, therefore not only increasing the infiltration of immunopositive cells from the outside but also reducing the immunosuppressive cells from the inside to break through the bottleneck of immune activation. The FS@PMPt nanocluster regulates the immune process in TME from negative to positive, from shallow to deep, to turn the cold tumor into a hot tumor and provoke a robust antitumor immune response.
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http://dx.doi.org/10.1073/pnas.2011297117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780000PMC
December 2020

Heme Oxygenase-1 suppresses duck Tembusu virus replication in vitro.

Vet Microbiol 2020 Dec 10;251:108885. Epub 2020 Oct 10.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China; College of Veterinary Medicine, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China. Electronic address:

Heme Oxygenase-1 (HO-1) is a ubiquitously expressed enzyme which plays important functions in antioxidant, anti-inflammatory and anti-apoptosis. Recent studies have demonstrated that HO-1 also has significant antiviral properties, inhibiting the replication of some kinds of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and dengue fever virus (DFV). In this study, we evaluated the role of HO-1 in Duck Tembusu virus (DTMUV) replication in vitro. The results showed that, the mRNA expression level of HO-1 was transient up-regulated and then significantly decreased in duck embryo fibroblast (DEF) infected with DTMUV. HO-1 induction by transfection of HO-1 over-expression plasmid or treatment with cobalt protoporphyrin (CoPP), a potent HO-1 inducer, could inhibit DTMUV replication effectively. In contrast, HO-1 siRNA knockdown in DEF increased DTMUV replication, implied that HO-1 was an important cellular factor against DTMUV replication. Furthermore, we found that ferric ion (Fe) but not biliverdin and carbon monoxide, products of heme degradation by HO-1, mediated the HO-1-induced anti-DTMUV effect. Overall, these finding revealed that a drug induced the HO-1 signal pathway was a promising strategy for treating DTMUV infection.
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http://dx.doi.org/10.1016/j.vetmic.2020.108885DOI Listing
December 2020

Carbon tetrachloride (CCl) accelerated development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) in MS-NASH mice fed western diet supplemented with fructose (WDF).

BMC Gastroenterol 2020 Oct 15;20(1):339. Epub 2020 Oct 15.

Crown Bioscience (CBLA), New Iberia, Louisiana, USA.

Background: Multiple murine models of nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) have been established by using obesogenic diets and/or chemical induction. MS-NASH mouse (formally FATZO) is a spontaneously developed dysmetabolic strain that can progress from hepatosteatosis to moderate fibrosis when fed a western diet supplemented with 5% fructose (WDF). This study aimed to use carbon tetrachloride (CCl) to accelerate and aggravate progression of NAFLD/NASH in MS-NASH mouse.

Methods: Male MS-NASH mice at 8 weeks of age were fed WDF for the entire study. Starting at 16 weeks of age, CCl was intraperitoneally administered twice weekly at a dose of 0.2 mL/kg for 3 weeks or 0.08 mL/kg for 8 weeks. Obeticholic acid (OCA, 30 mg/kg, QD) was administered in both MS-NASH and C57Bl/6 mice fed WDF and treated with CCl (0.08 mL/kg).

Results: WDF enhanced obesity and hepatosteatosis, as well as induced moderate fibrosis in MS-NASH mice similar to previous reports. Administration of CCl accelerated liver fibrosis with increased bridging and liver hydroxyproline contents, but had no significant impact on liver steatosis and lipid contents. High dose CCl caused high mortality and dramatic elevation of ALT and ASL, while low dose CCl resulted in a moderate elevation of ALT and AST with low mortality. Compared to C57BI/6 mice with WDF and CCl (0.08 mL/kg), MS-NASH mice had more prominent hepatosteatosis and fibrosis. OCA treatment significantly lowered liver triglycerides, steatosis and fibrosis in both MS-NASH and C57Bl/6 mice fed WDF with CCl treatment.

Conclusions: CCl reduced induction time and exacerbated liver fibrosis in MS-NASH mice on WDF, proving a superior NASH model with more prominent liver pathology, which has been used favorably in pharmaceutical industry for testing novel NASH therapeutics.
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http://dx.doi.org/10.1186/s12876-020-01467-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560288PMC
October 2020

The state of the art in kidney and kidney tumor segmentation in contrast-enhanced CT imaging: Results of the KiTS19 challenge.

Med Image Anal 2021 01 2;67:101821. Epub 2020 Oct 2.

University of Minnesota, Minneapolis, United States.

There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.
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http://dx.doi.org/10.1016/j.media.2020.101821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734203PMC
January 2021

SARS-CoV-2 Induces a More Robust Innate Immune Response and Replicates Less Efficiently Than SARS-CoV in the Human Intestines: An Ex Vivo Study With Implications on Pathogenesis of COVID-19.

Cell Mol Gastroenterol Hepatol 2021 1;11(3):771-781. Epub 2020 Oct 1.

State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China. Electronic address:

Background And Aims: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile.

Methods: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines.

Results: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues.

Conclusion: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.
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http://dx.doi.org/10.1016/j.jcmgh.2020.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527315PMC
March 2021

Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study.

Lancet Microbe 2020 May 21;1(1):e14-e23. Epub 2020 Apr 21.

Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus-host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown.

Methods: We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA.

Findings: SARS-CoV-2 infected and replicated to comparable levels in human Caco2 cells and Calu3 cells over a period of 120 h (p=0·52). By contrast, SARS-CoV infected and replicated more efficiently in Caco2 cells than in Calu3 cells under the same multiplicity of infection (p=0·0098). SARS-CoV-2, but not SARS-CoV, replicated modestly in U251 (neuronal) cells (p=0·036). For animal species cell tropism, both SARS-CoV and SARS-CoV-2 replicated in non-human primate, cat, rabbit, and pig cells. SARS-CoV, but not SARS-CoV-2, infected and replicated in bat kidney cells. SARS-CoV-2 consistently induced significantly delayed and milder levels of cell damage than did SARS-CoV in non-human primate cells (VeroE6, p=0·016; FRhK4, p=0·0004).

Interpretation: As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV.

Funding: May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, Respiratory Viral Research Foundation, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, The Hong Kong Hainan Commercial Association South China Microbiology Research Fund, The Jessie & George Ho Charitable Foundation, Perfect Shape Medical, The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, The Theme-Based Research Scheme of the Research Grants Council, Sanming Project of Medicine in Shenzhen, and The High Level-Hospital Program, Health Commission of Guangdong Province, China.
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http://dx.doi.org/10.1016/S2666-5247(20)30004-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173822PMC
May 2020

Paclitaxel, Carboplatin, and Bevacizumab in Advanced Cervical Cancer: A Treatment Response and Safety Analysis.

Dose Response 2020 Jul-Sep;18(3):1559325820941351. Epub 2020 Jul 29.

Department of Pharmacy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Medicine School of University of Electronic Science and Technology, Chengdu, People's Republic of China.

Background: Trials reported there are beneficial effects of the addition of bevacizumab to chemotherapy in advanced cervical cancer but might have adverse effects. The purposes of the study were to evaluate the treatment response and safety of the addition of bevacizumab to paclitaxel plus carboplatin in advanced cervical cancer women.

Methods: Data on treatment response, adverse effects, and overall survival of women who received paclitaxel plus carboplatin every 3 weeks (ACT cohort, n = 161) or paclitaxel, carboplatin, and bevacizumab every 3 weeks (PCB cohort, n = 127) until disease progression or severe adverse events were collected and analyzed.

Results: The treatment response of paclitaxel plus carboplatin increased on addition of bevacizumab ( = .037). Neutropenia (grade ≥3, = .001), leukopenia (grade 4, = .041), anemia (grade ≥3, = .031), hypertension (grade ≥2, = .002), and gastrointestinal fistula (grade ≥2, = 0.006) are reported in the PCB cohort. Women of ACT and PCB cohorts reported an overall survival of 20.11 ± 3.15 months and 24.52 ± 4.05 months, respectively.

Conclusions: Addition of bevacizumab increases the treatment response of paclitaxel and carboplatin chemotherapy and overall survival of women with advanced cervical cancers, but it is not well tolerated.
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http://dx.doi.org/10.1177/1559325820941351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391439PMC
July 2020

Methamphetamine induced neuroinflammation in mouse brain and microglial cell line BV2: Roles of the TLR4/TRIF/Peli1 signaling axis.

Toxicol Lett 2020 Oct 5;333:150-158. Epub 2020 Aug 5.

Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China; China International Cooperation Center for Environment and Human Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China. Electronic address:

Methamphetamine (Meth), a highly addictive drug, can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. Meth's effects on modulating microglial neuroimmune functions and eliciting neuroinflammation have attracted considerable attention in recent years. Recent evident of the effect of the non-dependent domain containing adaptor inducing interferon (TRIF)/Pellino1 (Peli1) signaling axis on pro-inflammatory cytokine production provides novel clues for inflammation. Therefore, our study investigated Meth-induced neurotoxicity from a neuropathological perspective by examining TLR4-TRIF-Peli1 axis signaling activation. Meth significantly activated microglia accompanied by marked increase of TLR4 and TRIF expression, NF-kB and MAPK pathways activation and the production of IL-1β, TNF-α and IL-6. Peli1 was involved in Meth-mediated neuroinflammation and knockdown of Peli1 strongly reversed NF-kB and MAPK pathways activation and pro-inflammatory cytokine excretion. Intriguingly, Peli1 upregulation induced by Meth was dependent on TRIF rather than the myloid differentiation factor 88 (MyD88) pathway, since the silencing of TRIF significantly suppressed Meth-induced Peli1 upregulation, while MyD88 knockdown had no obvious impact. Additionally, an in vivo study verified TLR4-TRIF-Peli1 axis activation and an enhanced level of downstream cytokine expression in the cortex after Meth treatment. Therefore, these findings provide new insight regarding the specific contributions of the TRIF-Peli1 pathway to Meth-mediated neuroinflammation.
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http://dx.doi.org/10.1016/j.toxlet.2020.07.028DOI Listing
October 2020

Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer.

J Infect 2020 10 21;81(4):e1-e10. Epub 2020 Jul 21.

Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. Electronic address:

Objectives: Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking.

Methods: We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV.

Results: Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL interferon-β (IFNβ) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFNβ and IFN inducer than SARS-CoV in Calu3.

Conclusions: Despite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.
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http://dx.doi.org/10.1016/j.jinf.2020.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373021PMC
October 2020

Evaluation of an artificial intelligent hydrocephalus diagnosis model based on transfer learning.

Medicine (Baltimore) 2020 Jul;99(29):e21229

Department of Neurosurgery, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang.

To design and develop artificial intelligence (AI) hydrocephalus (HYC) imaging diagnostic model using a transfer learning algorithm and evaluate its application in the diagnosis of HYC by non-contrast material-enhanced head computed tomographic (CT) images.A training and validation dataset of non-contrast material-enhanced head CT examinations that comprised of 1000 patients with HYC and 1000 normal people with no HYC accumulating to 28,500 images. Images were pre-processed, and the feature variables were labeled. The feature variables were extracted by the neural network for transfer learning. AI algorithm performance was tested on a separate dataset containing 250 examinations of HYC and 250 of normal. Resident, attending and consultant in the department of radiology were also tested with the test sets, their results were compared with the AI model.Final model performance for HYC showed 93.6% sensitivity (95% confidence interval: 77%, 97%) and 94.4% specificity (95% confidence interval: 79%, 98%), with area under the characteristic curve of 0.93. Accuracy rate of model, resident, attending, and consultant were 94.0%, 93.4%, 95.6%, and 97.0%.AI can effectively identify the characteristics of HYC from CT images of the brain and automatically analyze the images. In the future, AI can provide auxiliary diagnosis of image results and reduce the burden on junior doctors.
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http://dx.doi.org/10.1097/MD.0000000000021229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373556PMC
July 2020

Trial designs for evaluating combination HIV prevention approaches.

HIV Res Clin Pract 2020 Apr - Jun;21(2-3):72-82. Epub 2020 Jul 23.

Department of Biostatistics, University of Washington, Seattle, WA, USA.

Background: Combination HIV prevention approaches that include both biomedical and non-biomedical interventions often hold greater promise to improve health outcomes and reduce the risk of HIV transmission.

Objectives: Evaluate the relative properties of four leading candidate trial designs - 'single-factor', 'multi-arm', 'all-in-one', and 'factorial' designs - for assessing individual and/or combination prevention intervention approaches.

Methods: Monte-Carlo simulations are conducted, assuming a putative combination approach could choose its components from two candidate biomedical interventions, i.e. Treatment-as-Prevention (TasP) and Pre-exposure Prophylaxis (PrEP), and three candidate behavioral interventions, i.e. linkage-to-care, counseling, and use of condoms. Various scenarios for individual components' effect sizes, their possible interaction, and the sample size based on real clinical studies are considered.

Results: The all-in-one and factorial designs used to assess a combination approach and the multi-arm design used to assess multiple individual components are consistently more powerful than single-factor designs. The all-in-one design is powerful when the individual components are effective without negative interaction, while the factorial design is more consistently powerful across a broad array of settings.

Conclusions: The multi-arm design is useful for evaluating single factor regimens, while the all-in-one and factorial designs are sensitive in assessing the overall efficacy when there is interest in combining individual component regimens anticipated to have complementary mechanisms. The factorial design is a preferred approach when assessing combination regimens due to its favorable power properties and since it is the only design providing direct insights about the contribution of individual components to the combination approach's overall efficacy and about potential interactions.
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http://dx.doi.org/10.1080/25787489.2020.1798083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608072PMC
July 2020

Avian leukosis virus contamination in live vaccines: A retrospective investigation in China.

Vet Microbiol 2020 Jul 11;246:108712. Epub 2020 May 11.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, Shandong, China. Electronic address:

Avian leukosis (AL) is one of the most pandemic immunosuppressive diseases and has been widely spread between 2006 and 2009 in China. The contamination of avian leukosis virus (ALV) in attenuated vaccine is considered as one of the possible transmission routes of this disease. Based on a retrospective survey of 918 batches of attenuated vaccine produced before 2010, three of them were identified as ALV-positive and corresponding ALV strains were successfully isolated from a live Fowlpox virus vaccine, a live Newcastle disease virus vaccine and a live Infectious Bursal Disease virus vaccine, respectively, and whole-genome sequencing showed that these three isolates shared the highest homology with ALV-A wild strains isolated in China (97.7%) over the same period, and the phylogenetic analysis based on their gp85 genes further confirmed that they belong to subgroup A. Meanwhile, although these three ALV-A strains isolated from contaminated vaccines shared a close genetic relationship, their U3 region of genome have a relatively low identity, suggesting that these three strains may have different sources. This study reminds us once again that the possibility of ALV infecting chickens through contaminated live vaccines, requiring us to carry out stricter exogenous virus monitoring in vaccines.
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http://dx.doi.org/10.1016/j.vetmic.2020.108712DOI Listing
July 2020

Silver-decorated mesostructured cellular silica foams as excellent antibacterial hemostatic agents for rapid and effective treatment of hemorrhage.

Mater Sci Eng C Mater Biol Appl 2020 Oct 20;115:111105. Epub 2020 May 20.

Department of Emergency, Changhai Hospital, the Naval Medical University, Shanghai, China; Department of Orthopedics, Changhai Hospital, the Naval Medical University, Shanghai, China. Electronic address:

Uncontrolled bleeding, such as deep, narrow or irregular wound hemorrhage, has been a major cause of death in peacetime and wartime. Besides, traditional hemostatic agents are lack of antibacterial properties, which could not provide effective protection on open wound. In this paper, a novel antibacterial hemostatic agent composed of mesostructured cellular silica foams (MCF) decorated with silver ions (MCF-Ag) was synthesized by hydrothermal method. Hemorrhage wound infected with Escherichia coli was applied to evaluate its antibacterial and hemostatic performance both in vitro and in vivo. Both MCF and MCF-Ag showed excellent hemostasis in vitro and in vivo. The MCF-Ag demonstrated significant antibacterial effect. By contrast, no obvious antibacterial effect was observed from the MCF. The above results demonstrate that the MCF-Ag is an excellent antibacterial hemostatic agent with splendid water absorption and antibacterial capacity.
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http://dx.doi.org/10.1016/j.msec.2020.111105DOI Listing
October 2020

The effects of fluoroalkyl chain length and density on siRNA delivery of bioreducible poly(amido amine)s.

Eur J Pharm Sci 2020 Sep 23;152:105433. Epub 2020 Jun 23.

Institute of Comparative Medicine, College of Veterinary Medicine, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. Electronic address:

Fluorination is an attractive strategy for the improvement of transfection efficiency of nucleic acid delivery vectors. Bioreducible poly(amido amine)s (bPAAs) are an important class of biomaterials exhibited to effectively deliver multiple nucleic acids. However, still, the effects of fluoroalkyl chain length and density of bPAA on siRNA delivery are unveiled. Here, we synthesized bPAAs and grafted with different chain lengths and densities of fluorocarbon compounds. Furthermore, we prepared a library of complexes of fluorinated bPAA and siRNA, and investigated the effects of fluorination on the siRNA delivery in vitro and in vivo. We found that all the synthesized bPAAs readily formed complexes with siRNA and the fluorinated complexes considerably achieved improved gene silencing efficacies both in vitro and in vivo. Dramatically, the gene silencing efficacy was increased with increasing fluorine contents. Heptafluorobutyric anhydride (HF) modified bPAAs achieved better gene silencing efficacy when compared with bPAAs fluorinated by trifluoroacetic anhydride (TF) and pentafluoropropionic anhydride (PF) providing the evidence for choosing of best one among fluorocarbon compounds. In addition, a combination of fluorination with bioreducibility enables efficient and safe siRNA delivery.
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http://dx.doi.org/10.1016/j.ejps.2020.105433DOI Listing
September 2020

Attenuated Interferon and Proinflammatory Response in SARS-CoV-2-Infected Human Dendritic Cells Is Associated With Viral Antagonism of STAT1 Phosphorylation.

J Infect Dis 2020 08;222(5):734-745

State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

Clinical manifestations of coronavirus disease 2019 (COVID-19) vary from asymptomatic virus shedding, nonspecific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The interplay between SARS-CoV-2 and these cell types remains unknown. We investigated infection and host responses of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. MoDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types and triggered significant proinflammatory cytokine/chemokine expression in MDMs but not moDCs. Investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings may explain the mild and insidious course of COVID-19 until late deterioration.
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http://dx.doi.org/10.1093/infdis/jiaa356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337793PMC
August 2020

Onion Epithelial Membrane Scaffolds Transfer Corneal Epithelial Layers in Reconstruction Surgery.

Adv Healthc Mater 2020 07 16;9(14):e2000469. Epub 2020 Jun 16.

Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.

Plants and their extracts have been used especially in China for more than ten centuries for preventing and treating disease. However, there are only few reports describing their use in animal cell culture and tissue transplantation. In this study, onion epithelial membranes (OEM) is used as scaffolds to support cultures of a variety of cells such as fibroblasts and epithelial cells notably; they maintain the phenotypic characteristics of corneal epithelial cells. This improvement includes preservation of the proliferative potential and stemness of rabbit corneal epithelial cells (RCECs). Such an outcome suggests that this cost-effective technology warrants further evaluation to determine if OEM is a viable candidate for use as scaffolds in corneal epithelial transplantation surgery. To test this possibility, rabbit corneal epithelial cells expanded on OEM are transplanted to treat corneal epithelial defects in limbal stem cell deficient rabbits. This procedure is successful because it shortens the time required for wound healing to restore losses in corneal epithelial integrity, and forms a more compact and stratified epithelium framework than the untreated group. Ultimately, should they be proven to be effective in other relevant animal model systems, their usefulness for treating wounds in a clinical setting warrants consideration.
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http://dx.doi.org/10.1002/adhm.202000469DOI Listing
July 2020

Potential risks of SARS-CoV-2 infection on reproductive health.

Reprod Biomed Online 2020 07 30;41(1):89-95. Epub 2020 Apr 30.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital Beijing, China; National Clinical Research Center for Obstetrics and Gynecology Beijing, China. Electronic address:

The outbreak of 2019 novel coronavirus disease (COVID-19) has become a major pandemic threat worldwide. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focuses on its potential risks for reproductive health, including the reproductive system and its functioning, as well as gamete and embryo development, which could be affected by the virus itself, drug treatments, chemical disinfectants and psychological effects related to panic during the COVID-19 outbreak.
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http://dx.doi.org/10.1016/j.rbmo.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192111PMC
July 2020