Publications by authors named "Bing Zhang"

2,010 Publications

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Effects of Bacillus Coagulans on growth performance, antioxidant capacity, immunity function, and gut health in broilers.

Poult Sci 2021 Mar 27;100(6):101168. Epub 2021 Mar 27.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health and Internet Technology, College of Animal Science and Technology, Zhejiang Agriculture & Forestry University, Hangzhou 311300, China. Electronic address:

This study evaluated the effects of Bacillus coagulans (B. coagulans) as an alternative to antibiotics on growth performance, antioxidant capacity, immunity function and gut health in broilers. A total of 480 one-day-old broilers were randomly divided into 3 treatments with 8 replicates comprising 20 broilers each. The experiment lasted 42 d. Treatments included: basal diet without antibiotics (NCO); basal diet supplemented with 75 mg/kg chlortetracycline (ANT); basal diet supplemented with 5 × 10 CFU/kg B. coagulans(BC). The B. coagulans enhanced body weight (BW) and average daily gain compared with the NCO group (P < 0.05). However, there were no significant differences in average daily feed intake and feed: gain ratio (F: G) among three groups (P > 0.05). The B. coagulans significantly increased catalase, superoxide dismutase, and glutathione peroxidase levels and reduced malondialdehyde levels (P < 0.05). The serum immunoglobulins (IgA, IgM, and IgY) were significantly higher in the BC group when compared to the NCO and ANT groups (P < 0.05). The B. coagulans also markedly reduced serum levels of proinflammatory factors (IL-1β, IL-6, and TNF-α) and enhanced anti-inflammatory factor (IL-10) concentrations compared with control group (P < 0.05). Moreover, compared with the control group, BC significantly inhibited serum xanthine oxidase activity (P < 0.05). The levels of acetic acid, propionic acid, butyrate, isobutyric acid and valerate in BC group were significantly increased on d 42 compared with the NCO and ANT groups (P < 0.05). Furthermore, BC significantly altered cecal microbiota by reducing Desulfovibrio and Parasutterella, and by increasing Alistipes and Odoribacter (P < 0.05, P < 0.05, P < 0.001, P < 0.01, respectively). In conclusion, dietary B. coagulans, when used as an alternative to antibiotics, improved body weight, average daily gain, antioxidant capacity, immunity function and gut health in broilers.
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http://dx.doi.org/10.1016/j.psj.2021.101168DOI Listing
March 2021

Can public-private partnerships (PPPs) improve the environmental performance of urban sewage treatment?

J Environ Manage 2021 May 7;291:112660. Epub 2021 May 7.

State Key Laboratory of Pollution Control & Resource Reuse, School of Environment, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology (CICAEET), Nanjing University of Information Science & Technology, Nanjing 210044, PR China. Electronic address:

Insufficient sewage treatment facility is one important reason for wastewater entering and affecting aquatic ecosystems. The PPP mode, serving as one of the fastest-growing mechanisms for public service provision in recent decades, is considered to be an effective way to alleviate the pressure of funding shortages and to improve the efficiency of sewage treatment. However, the performance of PPPs has been questioned, especially the service quality given the inherent nature of the private sectors' pursuit of maximizing economic profit and the shortcoming of incomplete contracts. This paper evaluates the service quality, namely the environmental performance, of the PPP mode in China's urban sewage treatment sector. Based on detailed firm-level data in Jiangsu Province, China, we find that the PPP mode has improved the pollutant treatment performance, and increased operation cost and promoted sewage treatment efficiency serve as the main mechanism for the improvement of environmental performance. The research findings could help both developed and developing countries to apply and design a public-private partnerships mechanism.
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http://dx.doi.org/10.1016/j.jenvman.2021.112660DOI Listing
May 2021

Molecular characterization and biological function of CXCR1 in Nocardia seriolae-infected largemouth bass (Micropterus salmoides).

Tissue Cell 2021 Apr 21;72:101551. Epub 2021 Apr 21.

Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang, 316022, People's Republic of China. Electronic address:

Interleukin-8 (IL-8, CXCL8), a pro-inflammatory chemokine secreted by a variety of cell types, plays a critical role in the development of various immune diseases. Interactions between IL-8 and its receptor CXC receptor 1/2 (CXCR1/2) are known to promote chemotaxis and phagocytosis in many immune responses. In this study, we report the molecular characteristics and pharmacological activity of CXCR1 (MsCXCR1) in largemouth bass (Micropterus salmoides) and evaluated the functional involvement of MsCXCR1 in individuals infected with the pathogen Nocardia seriolae. MsCXCR1 was cloned into the pEGFP-N1 plasmid and the subcellular localization of MsCXCR1 on the cell membrane was verified in MsCXCR1-EGFP-expressing HEK293 cells. Following observation of receptor internalization and intracellular signaling detection, we further determined the functional interaction of secreted interleukin-8 (LcIL-8, the ligand for CXCR1 in large yellow croaker) and MsCXCR1 was further determined, and the ERK phosphorylation signal activation mediated by MsCXCR1 was demonstrated. Quantitative real-time PCR assays were conducted to analyze the transcriptional distribution of MsCXCR1 in various tissues of healthy and diseased largemouth bass. These results illustrate the significant elevation of MsCXCR1 expression in the head kidney, spleen and liver of M. salmoides, suggesting that MsCXCR1 was involved in the immune response in N. seriolae-infected largemouth bass and potentially affects the digestive function of this species.
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http://dx.doi.org/10.1016/j.tice.2021.101551DOI Listing
April 2021

Twenty-Five-Year Trends in Dietary Patterns among Chinese Adults from 1991 to 2015.

Nutrients 2021 Apr 16;13(4). Epub 2021 Apr 16.

Department of Public Nutrition, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Poor dietary habits have been shown to be associated with a range of chronic diseases and can potentially be a major contributor to non-communicable diseases (NCDs) mortality. We therefore aimed to identify the prevailing dietary patterns among Chinese adults and to evaluate trends in dietary patterns from 1991 to 2015. We used data collected in the China Health and Nutrition Survey (CHNS). Dietary patterns were identified using factor analysis of data from three consecutive 24 h dietary recalls. We studied 29,238 adults aged 18 and above with complete demo-graphic and dietary data. Three distinct dietary patterns were identified: southern (high intakes of rice, vegetables, and pork), modern (high intakes of fruits, dairy products, cakes, cookies, and pastries), and meat (high intakes of organ meats, poultry, and other livestock meat). The southern pattern score decreased (mean ± SD scores in 1991: 0.11 ± 1.13; scores in 2015: -0.22 ± 0.93). The modern pattern score (mean ± SD scores in 1991: -0.44 ± 0.59; scores in 2015: 0.21 ± 1.01) and meat pattern score (mean ± SD scores in 1991: -0.18 ± 0.98; scores in 2015: 0.27 ± 0.91) increased. We observed that China has experienced a shift from traditional dietary patterns to western dietary patterns.
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http://dx.doi.org/10.3390/nu13041327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072541PMC
April 2021

Enhanced Anticancer Efficacy of Dual Drug-Loaded Self-Assembled Nanostructured Lipid Carriers Mediated by pH-Responsive Folic Acid and Human-Derived Cell Penetrating Peptide dNP2.

Pharmaceutics 2021 Apr 22;13(5). Epub 2021 Apr 22.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

The poor ability of recognition and penetration of chemotherapeutic agents to tumor cells are still great challenges for targeted breast cancer treatment. Herein, we established a tumor-targeted nanostructured lipid carrier encapsulating gambogic acid (GA) and paclitaxel (PTX), which was co-modified with acid-cleavable folic acid (cFA) and a human-derived cell penetrating peptide dNP2 (CKIKKVKKKGRKKIKKVKKKGRK). The multi-functional nano-platform exhibited an enhanced targeting and penetrability to tumor tissues, which was accomplished by the combined action of cFA and dNP2. After intravenous injection, firstly, cFA could actively target the breast cancer tissues by the selective recognition of folate receptor (FR); then, upon arrival at the tumor microenvironment, the acid-cleavable FA and dNP2 dual modified nanostructured lipid carrier (cFA/dNP2-GA/PTX-NLC) exhibited sensitive cleavage of folic acid (FA), which could reduce the hindrance effect of FA to maximize the dNP2 cell-penetrating properties. The effect of different modification on cellular uptake, in vivo bio-distribution, and anticancer activity of NLCs proved our hypothesis that compared with NLCs modified by non-cleavable FA or a single ligand, cFA/dNP2-GA/PTX-NLC displayed more efficient intracellular delivery, stronger targeting ability in vivo, improved cytotoxicity on 4T1 cells, and produced the better therapeutic efficacy of GA and PTX. The strategy affords a feasible way to overcome the poor recognition and permeability of medicines in cancer treatment.
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http://dx.doi.org/10.3390/pharmaceutics13050600DOI Listing
April 2021

Diet-Cognition Associations Differ in Mild Cognitive Impairment Subtypes.

Nutrients 2021 Apr 17;13(4). Epub 2021 Apr 17.

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing 100050, China.

Cognitive function is not generally associated with diet, and there is debate over that association. Moreover, little is known about such associations with the specific cognitive domains and subtypes of mild cognitive impairment (MCI). We analyzed data of 4309 Chinese adults aged 55 and over from the Community-based Cohort Study on Nervous System Diseases from 2018-2019. Dietary habits were assessed at inclusion using a validated semi-quantitative food frequency questionnaire. Cognitive function of the participants was measured by using the Montreal Cognitive Assessment. Analyses were performed using multiple logistic regression and quantile regression with adjustment for socio-demographic, lifestyle, and health-related factors. Compared with normal cognition participants, those with a worse cognition state were characterized as being an older age and lower economic level. After adjustment for potential factors, participants with higher consumption of rice, legumes, fresh vegetables, fresh fruit, pork, poultry, fish, and nuts tended to have higher scores of global cognitive function and domains, and to have lower odds of MCI, while those with higher consumption levels of wheat and eggs had worse cognition, compared with the corresponding bottom consumption level of each food. Participants with a medium consumption level of beef or mutton had 57% (OR: 1.57, 95%CI: 1.07-2.32) higher odds of aMCI-SD, whereas they had 50% (OR: 0.50, 95%CI: 0.34-0.73) lower odds of naMCI-MD. Similarly, the highest consumption level of dairy was positively associated with the odds of aMCI-SD (OR:1.51, 95%CI:1.00-2.29), but inversely linked to the odds of naMCI-SD (OR: 0.60, 95%CI: 0.38-0.93) and naMCI-MD (OR: 0.49, 95%CI: 0.29-0.82). Most diet global cognitive benefits were observed to be associated with the preexisting higher consumption of rice, legumes, fresh vegetables, fresh fruit, meat, and nuts. In addition, the heterogeneity of associations between the consumption of certain foods and MCI subtypes was observed among Chinese adults aged over 55 years. These cross-sectional observations require validation in prospective studies.
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http://dx.doi.org/10.3390/nu13041341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073801PMC
April 2021

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8 T and NK cells: a novel therapeutic tumour vaccine.

J Hematol Oncol 2021 Apr 28;14(1):71. Epub 2021 Apr 28.

Department of Pharmacology, School of Pharmacy, China Medical University, No. 13, Beihai Road, Dadong District, Shenyang, Liaoning Province, China.

Background: CD8 T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8 T and NK cells.

Methods: The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Flow cytometry, confocal microscopy, UPLC-QTOF-MS, and RNA-seq were utilized for evaluating immunity of PBMC-derived DCs, CD8 T or NK cells and related pathways. HLA-A2.1 transgenic mice combined with immunologically reconstituted tumour-bearing mice were used to examine the antitumour effect and safety of epitope vaccines.

Results: We identified novel HLA-A2.1-restricted extracellular matrix protein 1(ECM1)-derived immunodominant epitopes in which LA induced a potent immune response. We also found that LA-loaded DCs upregulated the frequency of CD3/CD8 T cells, CD45RO/CD69 activated memory T cells, and CD3/CD16/CD56 NK cells. We demonstrated cytotoxic granule release of LA/DC-CTLs or LA/DC-NK cells and cytotoxicity against tumour cells and microtissue blocks via the predominant IFN-γ/perforin/granzyme B cell death pathway. Further investigating the mechanism of LA-mediated CD8 T activation, we found that LA could be internalized into DCs through phagocytosis and then formed a LA-MHC-I complex presented onto the DC surface for recognition of the T cell receptor to upregulate Zap70 phosphorylation levels to further activate CD8 T cells by DC-CTL interactions. In addition, LA-mediated DC-NK crosstalk through stimulation of the TLR4-p38 MAPK pathway increased MICA/B expression on DCs to interact with NKG2D for NK activation. Promisingly, LA could activate CD8 T cells and NK cells simultaneously via interacting with DCs to suppress tumours in vivo. Moreover, the safety of LA was confirmed.

Conclusions: LA-induced immune antitumour activity through DC cross-activation with CD8 T and NK cells, which demonstrated proof-of-concept evidence for the capability and safety of a novel therapeutic tumour vaccine.
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http://dx.doi.org/10.1186/s13045-021-01081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082934PMC
April 2021

Proteome analysis of bermudagrass stolons and rhizomes provides new insights into the adaptation of plant stems to aboveground and underground growth.

J Proteomics 2021 Jun 24;241:104245. Epub 2021 Apr 24.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address:

As an important perennial warm-season turfgrass species, bermudagrass (Cynodon dactylon L.) forms underground-growing rhizomes and aboveground-growing stolons simultaneously, making it a fast propagating clonal plant with strong regeneration ability. In the current study, we compared the internode proteomes of rhizomes and stolons at the same developmental stage in the bermudagrass cultivar Yangjiang using iTRAQ. The results indicated that 228 protein species were differentially accumulated in the two specialized stems. In agreement with the different contents of starch, chlorophyll, anthocyanin and HO in the two types of stems, photosynthesis and flavonoid biosynthesis were enriched with differentially accumulated protein species (DAPs) in stolons, whereas starch and sucrose metabolism, glycolysis, and HO metabolism were enriched with DAPs in rhizomes. Burying stolons in the soil resulted in the gradual degradation of chlorophyll and anthocyanin, accumulation of starch, and increment of HO, which is similar to the physiological characteristics of rhizomes. These results collectively revealed that stolons and rhizomes of bermudagrass have significant differences at the proteome level and light might play important regulatory roles in the discrepancy of the proteome profiles and specialization of the two stems, providing new insights into the adaptation of plant stems to aboveground and underground growth. BIOLOGICAL SIGNIFICANCE: As two types of specialized stems that grow underground and aboveground respectively, rhizomes and stolons play important roles in overwintering and ecological invasion of many perennial and clonal plants. However, because rhizomes and stolons rarely coexist in single plant species, the differences between the two stems remain unclear at the molecular level. In this study, through an iTRAQ comparative proteomic analysis, we reported the identification of 228 differentially accumulated protein species (DAPs) in rhizomes and stolons of bermudagrass for the first time. We found that the 228 DAPs were interconnected to form protein networks in regulating diverse cellular activities and biochemical reactions. We also observed that stolons growing underground showed similar physiological activities and DAP expression as those of underground-growing rhizomes, suggesting that light might play important regulatory roles in the specialization of stolons and rhizomes. These results expanded our understanding of the mysterious adaption of plant stems to different growth conditions.
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http://dx.doi.org/10.1016/j.jprot.2021.104245DOI Listing
June 2021

Design, synthesis and biological evaluation of novel FXIa inhibitors with 2-phenyl-1H-imidazole-5-carboxamide moiety as P1 fragment.

Eur J Med Chem 2021 Apr 20;220:113437. Epub 2021 Apr 20.

Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang, 110016, China. Electronic address:

Factor XIa, as a blood coagulation enzyme, amplifies the generation of the last enzyme thrombin in the blood coagulation cascade. It was proved that direct inhibition of factor XIa could reduce pathologic thrombus formation without an enhanced risk of bleeding. WSJ-557, a nonpurine imidazole-based xanthine oxidase inhibitor in our previous reports, could delay blood coagulation during its animal experiments, which prompted us to investigate its action mechanism. Subsequently, during the exploration of the action mechanism, it was found that WSJ-557 exhibited weak in vitro factor XIa binding affinity. Under the guide of molecular modeling, we adopted molecular hybridization strategy to develop novel factor XIa inhibitors with WSJ-557 as an initial compound. This led to the identification of the most potent compound 44g with a Ki value of 0.009 μM, which was close to that of BMS-724296 (Ki = 0.0015 μM). Additionally, serine protease selectivity study indicated that compound 44g display a desired selectivity, more 400-fold than those of thrombin, factor VIIa and factor Xa in coagulation cascade. Moreover, enzyme kinetics studies suggested that the representative compound 44g acted as a competitive-type inhibitor for FXIa, and molecular modeling revealed that it could tightly bind to the S1, S1' and S2' pockets of factor XIa. Furthermore, in vivo efficacy in the rabbit arteriovenous shunt model suggested that compound 44g demonstrated dose-dependent antithrombotic efficacy. Therefore, these results supported that compound 44g could be a potential and efficacious agent for the treatment of thrombotic diseases.
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http://dx.doi.org/10.1016/j.ejmech.2021.113437DOI Listing
April 2021

Validation of a Next-Generation Sequencing-based T-Cell Receptor Gamma Gene Rearrangement Diagnostic Assay: Transitioning from Capillary Electrophoresis to Next-Generation Sequencing.

J Mol Diagn 2021 Apr 20. Epub 2021 Apr 20.

Department of Pathology, Stanford University School of Medicine, Stanford, California, 94305, United States of America. Electronic address:

Assessment of T-cell receptor gamma (TRG) gene rearrangement is an important consideration in the diagnostic workup of lymphoproliferative diseases. Although fragment analysis by PCR and capillary electrophoresis (CE) is the current standard for such assessment in clinical molecular diagnostic laboratories, it does not provide sequence information and is only semi-quantitative. Next-generation sequencing (NGS)-based assays are an attractive alternative to the conventional fragment-size based methods since they generate results with specific clonotype sequence information and allow for more accurate quantitation. We therefore evaluated various test parameters and performance characteristics for a commercially available NGS-based TRG gene rearrangement assay by testing 101 clinical samples previously characterized by fragment analysis. The NGS TRG assay showed an overall accuracy of 83% and an analytical specificity of 100%, as compared to the CE-based assay. The concordance rate was 88∼95% for Vγ1-8, Vγ10 and Vγ11 gene families, but lower for the Vγ9 gene family. This difference was mostly attributed to the incomplete polyclonal symmetry resulting from the two-tube CE assay versus the one-tube design of the NGS assay. The NGS assay also demonstrated strengths in distinguishing different clonotypes with the same fragment size. Our clinical validation demonstrated robust performance of the NGS-based TRG assay and identified potential pitfalls associated with CE assay design that are important for understanding the observed discrepancies with the CE-based assay.
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http://dx.doi.org/10.1016/j.jmoldx.2021.03.008DOI Listing
April 2021

A Case of Giant Right Atrium Diverticulum with Atrial Septal Defect.

Heart Surg Forum 2021 04 16;24(2):E369-E371. Epub 2021 Apr 16.

Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

Right atrium diverticulum is a rare congenital malformation. We present a previously unreported case of giant right atrium diverticulum (153 × 109 mm) in a 17-year-old female patient. Echocardiographic examination also showed an atrial septal defect (11 mm). Considering the risk of right atrium rupture, we performed femoral arteriovenous cannulation first, followed by median thoracotomy. The defect was repaired with an autologous pericardial patch. The patient recovered well after the operation, and this case is referential for surgical treatment of giant right atrium diverticulum.
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http://dx.doi.org/10.1532/hsf.3645DOI Listing
April 2021

Feature Selection Methods for Protein Biomarker Discovery from Proteomics or Multi-omics Data.

Mol Cell Proteomics 2021 Apr 19:100083. Epub 2021 Apr 19.

Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. Electronic address:

Untargeted mass spectrometry (MS)-based proteomics provides a powerful platform for protein biomarker discovery, but clinical translation depends on the selection of a small number of proteins for downstream verification and validation. Due to the small sample size of typical discovery studies, protein markers identified from discovery data may not be generalizable to independent datasets. In addition, a good protein marker identified using a discovery platform may be difficult to implement in verification and validation platforms. Moreover, although multi-omics characterization is being increasingly used in discovery cohort studies, there is no existing method for multi-omics-facilitated protein biomarker selection. Here, we present ProMS, a computational algorithm for protein marker selection. The algorithm is based on the hypothesis that a phenotype is characterized by a few underlying biological functions, each manifested by a group of co-expressed proteins. A weighted k- medoids clustering algorithm is applied to all univariately informative proteins to identify both co-expressed protein clusters and a representative protein for each cluster as markers. In two clinically-important classification problems, ProMS shows superior performance compared with existing feature selection methods. ProMS can be extended to the multi-omics setting (ProMS_mo) through a constrained weighted k-medoids clustering algorithm, and the protein panels selected by ProMS_mo show improved performance on independent test data compared with ProMS. In addition to superior performance, ProMS and ProMS_mo also have two unique strengths. First, the feature clusters enable functional interpretation of the selected protein markers. Second, the feature clusters provide an opportunity to select replacement protein markers, facilitating a robust transition to the verification and validation platforms. In summary, this study provides a unified and effective computational framework for selecting protein biomarkers using proteomics or multi-omics data. The software implementation is publicly available at https://github.com/bzhanglab/proms.
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http://dx.doi.org/10.1016/j.mcpro.2021.100083DOI Listing
April 2021

Modularization of grid cells constrained by the pyramidal patch lattice.

iScience 2021 Apr 17;24(4):102301. Epub 2021 Mar 17.

National Laboratory of Solid State Microstructures, Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China.

Grid cells provide a metric representation of self-location. They are organized into modules, showing discretized scales of grid spacing, but the underlying mechanism remains elusive. In this modeling study, we propose that the hexagonal lattice of pyramidal cell patches may underlie the discretization of grid spacing and orientation. In the continuous attractor network composed of interneurons, stellate and pyramidal cells, the hexagonal lattice of bump attractors is specifically aligned to the patch lattice under 22 conditions determined by the geometry of the patch lattice, while pyramidal cells exhibit synchrony to diverse extents. Given the bump attractor lattice in each module originates from those 22 scenarios, the experimental data on the grid spacing ratio and orientation difference between modules can be reproduced. This work recapitulates the patterns of grid spacing versus orientation in individual animals and reveals the correlation between microstructures and firing fields, providing a systems-level mechanism for grid modularity.
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http://dx.doi.org/10.1016/j.isci.2021.102301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042349PMC
April 2021

Atrophy in the Left Amygdala Predicted Drug Responses in Idiopathic Generalized Epilepsy Patients With Tonic-Clonic Seizures.

Front Neurosci 2021 31;15:640016. Epub 2021 Mar 31.

Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-GTCS) MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D TWI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs ( = 0.004, false discovery rate corrected) and SF patients ( = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC ( < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency ( = -0.324, = 0.030) and between shape ( = -0.438, = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency ( = -0.689, = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.
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http://dx.doi.org/10.3389/fnins.2021.640016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044327PMC
March 2021

Impaired olfactory neural circuit in patients with SLE at early stages.

Lupus 2021 Apr 15:9612033211005556. Epub 2021 Apr 15.

Department of Radiology, Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Objective: To investigate the changes of olfactory function and odor-induced brain activation in patients with systemic lupus erythematosus (SLE) at early stages compared with healthy controls.

Materials And Methods: Olfactory function and odor-induced brain activation in 12 SLE patients at early stages and 12 age, gender and education matched healthy controls were evaluated using olfactory behavior test and odor-induced task-functional magnetic resonance imaging (task-fMRI).

Results: No significant differences in olfactory behavior scores (including olfactory threshold, olfactory identification, and olfactory memory) were found in the patients with SLE at early stages compared with the healthy controls, while significantly decreased odor-induced activations in olfactory-related brain regions were observed in the patients. In the SLE group, the patients with better performance in the olfactory threshold test had significantly lower levels of anti-dsDNA antibody.

Conclusion: The current study demonstrated that significant alterations in odor-induced brain activations occurred prior to measurable olfactory decline in SLE at early stages, which provided a new method for early diagnosis of olfactory dysfunction in SLE.
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http://dx.doi.org/10.1177/09612033211005556DOI Listing
April 2021

The mitochondrial genome of () (Diptera: Limoniidae).

Mitochondrial DNA B Resour 2021 Mar 31;6(4):1321-1323. Epub 2021 Mar 31.

Department of Entomology, College of Plant Protection, China Agricultural University, Beijing, China.

The crane fly () Mao and Yang, belongs to subfamily Limnophilinae of family Limoniidae. This mitogenome of () was sequenced used next-generation sequencing (NGS), the new representative of the mitogenome of the subfamily. The nearly complete mitogenome is 14,858 bp totally, consisting of 13 protein-coding genes, 2 rRNAs and 22 transfer RNAs. All genes have the similar locations and strands with that of other published species of Limoniidae. The nucleotide composition biases toward A and T, which together made up 75.2% of the entirety. Bayesian inference analysis strongly supported the monophyly of Tipuloidea. It suggested that Pediciidae is the basal clade of Tipuloidea and the monophyletic Tipulidae was assigned as the sister to the monophyletic Cylindrotomidae. The phylogenetic relationship within Tipuloidea was as follows: Pediciidae + (Limoniidae + (Tipulidae + Cylindrotomidae)).
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http://dx.doi.org/10.1080/23802359.2021.1907808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018454PMC
March 2021

Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients.

Chin Med Sci J 2021 Mar;36(1):17-26

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430071, China.

Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (), 1.17 (95% , 0.95-1.44), =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted , 1.23 (95% , 0.98-1.55), = 0.075 in TG increase group; 0.78 (95% , 0.57-1.07), = 0.123 in LDL-C increase group; and 1.12 (95% , 0.9-1.39), = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.
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http://dx.doi.org/10.24920/003866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041136PMC
March 2021

An study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones.

Int J Hyperthermia 2021 ;38(1):593-603

Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada.

Purpose: To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models for a custom-made high-frequency irreversible electroporation (H-FIRE) generator.

Materials And Methods: A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols ( = 3 for each protocol) and an IRE protocol ( = 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively.

Results: All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3-1 μs, 2000 V, and 90-195 bursts) appears similar to that of IRE protocol (100 μs, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 μs, 2000 V, and 180 bursts).

Conclusion: Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.
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http://dx.doi.org/10.1080/02656736.2021.1912417DOI Listing
January 2021

Liraglutide-induced structural modulation of the gut microbiota in patients with type 2 diabetes mellitus.

PeerJ 2021 1;9:e11128. Epub 2021 Apr 1.

Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.

Accumulating evidence has suggested the importance of gut microbiota in the development of type 2 diabetes mellitus (T2DM). In the present study, 40 patients with T2DM were treated with liraglutide for 4 months. Feces samples and clinical characteristics were collected from these 40 T2DM patients before and after the liraglutide treatment. The diversity and composition of gut microbiota in the two groups were determined by sequencing the V4 region of bacterial 16S rRNA genes. Meanwhile, blood glucose, insulin, hemoglobin A1c (HbA1c), and lipid metabolism were also measured in the pre- and post-liraglutide-treatment groups. We find that Baseline HbA1c was associated with liraglutide treatment response ( = 0.527,  =  - 0.726,  < 0.0001). After adjusted for baseline HbA1c, blood urea nitrogen was associated with liraglutide treatment response. Besides, our results showed reduced gut microbial alpha diversity, different community structure distribution and altered microbial interaction network in patients treated with liraglutide. The liner discriminant analysis (LDA) effect size (LEfSe) analysis showed that 21 species of bacteria were abundant in the pre-liraglutide-treatment group and 15 species were abundant in the post-liraglutide-treatment group. In addition, we also find that were significantly correlated with older age, diabetes duration and diabetic retinopathy, were significantly correlated with family history of diabetes and were significantly correlated with both diabetic retinopathy and diabetic peripheral neuropathy. Functional analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and cluster of orthologous groups (COG) annotations enriched three KEGG metabolic pathways and six functional COG categories in the post-liraglutide-treatment group. In conclusion, our research suggests that baseline HbA1c, blood urea nitrogen and gut microbiota are associated with the liraglutide treatment applied on patients with T2DM. These findings may contribute to the beneficial effects of liraglutide against diabetes.
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http://dx.doi.org/10.7717/peerj.11128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019531PMC
April 2021

HF-UNet: Learning Hierarchically Inter-Task Relevance in Multi-Task U-Net for Accurate Prostate Segmentation in CT images.

IEEE Trans Med Imaging 2021 Apr 13;PP. Epub 2021 Apr 13.

Accurate segmentation of the prostate is a key step in external beam radiation therapy treatments. In this paper, we tackle the challenging task of prostate segmentation in CT images by a two-stage network with 1) the first stage to fast localize, and 2) the second stage to accurately segment the prostate. To precisely segment the prostate in the second stage, we formulate prostate segmentation into a multi-task learning framework, which includes a main task to segment the prostate, and an auxiliary task to delineate the prostate boundary. Here, the second task is applied to provide additional guidance of unclear prostate boundary in CT images. Besides, the conventional multi-task deep networks typically share most of the parameters (i.e., feature representations) across all tasks, which may limit their data fitting ability, as the specificity of different tasks are inevitably ignored. By contrast, we solve them by a hierarchically-fused U-Net structure, namely HF-UNet. The HF-UNet has two complementary branches for two tasks, with the novel proposed attention-based task consistency learning block to communicate at each level between the two decoding branches. Therefore, HF-UNet endows the ability to learn hierarchically the shared representations for different tasks, and preserve the specificity of learned representations for different tasks simultaneously. We did extensive evaluations of the proposed method on a large planning CT image dataset and a benchmark prostate zonal dataset. The experimental results show HF-UNet outperforms the conventional multi-task network architectures and the state-of-the-art methods.
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http://dx.doi.org/10.1109/TMI.2021.3072956DOI Listing
April 2021

Synthesis and biological evaluation of 2-(4-alkoxy-3-cyano)phenylpyrimidine derivatives with 4-amino or 4-hydroxy as a pharmacophore element binding with xanthine oxidase active site.

Bioorg Med Chem 2021 May 2;38:116117. Epub 2021 Apr 2.

Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang 110016, China. Electronic address:

Xanthine oxidase is the rate-limiting enzyme critical for the synthesis of uric acid, and therefore xanthine oxidase inhibitors are considered as one of the promising therapies for hyperuricemia and gout. In our previous study, series of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acids and 2-(4-alkoxy-3-cyano)phenyl-6-imino-1,6-dihydropyrimidine-5-carboxylic acids were synthesized that presented excellent in vitro xanthine oxidase inhibitory potency. Interestingly, molecular docking studies revealed that the interaction behavior of these compounds with xanthine oxidase was changed after the conversion from a hydroxy group to amine group. To further investigate the structure-activity relationships of these pyrimidine-containing xanthine oxidase inhibitors and explore the contribution of amino or hydroxy group on xanthine oxidase inhibitory potency, several 2-phenylpyrimidine derivatives with amino or hydroxy functional group were designed and synthesized. Thereafter, the structure-activity research and molecular modeling study proved that hydroxy and amino groups could be used as pharmacophore elements for the design of 2-phenylpyrimidines xanthine oxidase inhibitors. Particularly, the optimized compound, 2-(3-cyano-4-isopentoxy)phenylpyrimidine-4-ol, emerged the strongest xanthine oxidase inhibitor potency, with an IC value of 0.046 µM, which was approximately 120-fold more potent than that of allopurinol (IC = 5.462 µM). Additionally, Lineweaver-Burk plot analysis revealed that the optimized compound acted as a mixed-type inhibitor. Furthermore, the in vivo hypouricemic effect of the optimized compound was investigated in a hyperuricemia rat model induced by potassium oxonate, and the results showed that the optimized compound could effectively reduce serum uric acid levels at an oral dose of 30 mg/kg.
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http://dx.doi.org/10.1016/j.bmc.2021.116117DOI Listing
May 2021

Radiation-induced acute injury of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in induction chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a prospective cohort study.

Sci Rep 2021 Apr 8;11(1):7693. Epub 2021 Apr 8.

School of Public Health, Guangdong Pharmaceutical University, No. 283 Jianghai Avenue, Haizhu District, Guangzhou, 510310, China.

To address whether the addition of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT) aggravate radiation-induced acute injury of locoregionally advanced nasopharyngeal carcinoma (LANPC) patients with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). We conducted a prospective study of 182 patients in the stage III to IVb with biopsy-proven nonmetastatic LANPC who newly underwent radiotherapy and sequentially received IC, followed by CCRT at our institution. Occurring time of radiation-induced toxicities were estimated and compared using the Kaplan-Meier method and Log-rank test. The most severe acute toxicities included oral mucositis in 97.25% and dermatitis in 90.11%. Subset analysis revealed that Grade 3-4 acute dermatitis were significantly higher in the IMRT than 3D-CRT. Oral mucositis and dermatitis were the earliest occurrence of acute injuries (2 years: 60.44% and 17.58%). Patients in IMRT group achieved significantly lower risk of bone marrow toxicity, but higher risk of leukopenia and gastrointestinal injury. Multivariate analyses also demonstrated that IMRT, female gender and hepatitis were the independent prognostic factors for bone marrow toxicity. In a combined regimen of IC followed by CCRT for the treatment of LANPC, IMRT seems to be an aggressive technique with a trend towards increased gastrointestinal and hematological toxicities, but decreased bone marrow toxicity than those treated with 3D-CRT. This study provides a comprehensive summary of prospective evidence reporting the side effects in the management of LANPC patients. We quantify the occurrence risks of chemoradiotherapy-induced acute injuries through analysis of time-to-event.
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http://dx.doi.org/10.1038/s41598-021-87170-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032760PMC
April 2021

MetricUNet: Synergistic image- and voxel-level learning for precise prostate segmentation via online sampling.

Med Image Anal 2021 Mar 23;71:102039. Epub 2021 Mar 23.

School of Biomedical Engineering, ShanghaiTech University, Shanghai, China; Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China; Department of Artificial Intelligence, Korea University, Seoul 02841, Republic of Korea. Electronic address:

Fully convolutional networks (FCNs), including UNet and VNet, are widely-used network architectures for semantic segmentation in recent studies. However, conventional FCN is typically trained by the cross-entropy or Dice loss, which only calculates the error between predictions and ground-truth labels for pixels individually. This often results in non-smooth neighborhoods in the predicted segmentation. This problem becomes more serious in CT prostate segmentation as CT images are usually of low tissue contrast. To address this problem, we propose a two-stage framework, with the first stage to quickly localize the prostate region, and the second stage to precisely segment the prostate by a multi-task UNet architecture. We introduce a novel online metric learning module through voxel-wise sampling in the multi-task network. Therefore, the proposed network has a dual-branch architecture that tackles two tasks: (1) a segmentation sub-network aiming to generate the prostate segmentation, and (2) a voxel-metric learning sub-network aiming to improve the quality of the learned feature space supervised by a metric loss. Specifically, the voxel-metric learning sub-network samples tuples (including triplets and pairs) in voxel-level through the intermediate feature maps. Unlike conventional deep metric learning methods that generate triplets or pairs in image-level before the training phase, our proposed voxel-wise tuples are sampled in an online manner and operated in an end-to-end fashion via multi-task learning. To evaluate the proposed method, we implement extensive experiments on a real CT image dataset consisting 339 patients. The ablation studies show that our method can effectively learn more representative voxel-level features compared with the conventional learning methods with cross-entropy or Dice loss. And the comparisons show that the proposed method outperforms the state-of-the-art methods by a reasonable margin.
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http://dx.doi.org/10.1016/j.media.2021.102039DOI Listing
March 2021

The Spatiotemporal Evolution Analysis of Ecosystem Pattern in Wenchuan (Magnitude 8.0) Earthquake Disaster Area, China.

Int J Environ Res Public Health 2021 03 3;18(5). Epub 2021 Mar 3.

College of Resource Environment and Tourism, Capital Normal University, Beijing 100048, China.

The ecological system is the basis of human survival and global environmental protection. In the process of development, countries will pay close attention to the changing state of the ecosystem. Taking the ecosystem pattern as the research object, a three-layer analysis method was proposed. The transfer matrix and landscape index were used as the first layer to analyze the basic changes. Grey correlation, range-coupling coordination and relative priority were used as the second layer to analyze the reasons of the change. The interval-entropy weight, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), was used as the third layer to evaluate the quality of the change. The ten counties in the worst-hit areas of the Wenchuan earthquake were analyzed from different angles, with county region, intensity zone and ecosystem as the objects, and the following results were obtained: (1) Taking Mianzhu City as an example, from 2000 to 2010 and 2018, the conversion ratio of forest, grassland and farmland is 54.24, 59.19, 17.21, 20.06, 37.39 and 52.86%, which were distributed in the north, central and southern parts, respectively. (2) Taking the ninth intensity zone as an example, the forest landscape fragmentation increased, disturbance decreased, and species diversity increased. There is a high influence and restriction relationship between ecosystem and landscape pattern in the total landscape area change. Additionally, the relationship between them tends to develop in a benign way. As of 2018, it is in the change state of moderate imbalance-ecosystem lag. (3) Taking the county ecosystem change as an example, urban type is the best in the counties of ecosystem change, of which Shifang is the best and Pingwu is the worst. The results show that this method can effectively compare and analyze the changes in the multi-regional ecosystem pattern, which has the characteristics of universality and can also be applied to the research of ecosystem pattern change in special regions.
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http://dx.doi.org/10.3390/ijerph18052490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967621PMC
March 2021

Effect of Different Exercise Methods on Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and Meta-Regression.

Int J Environ Res Public Health 2021 03 21;18(6). Epub 2021 Mar 21.

Division of Sports Science and Physical Education, Tsinghua University, Beijing 100081, China.

Exercise could alleviate non-alcoholic fatty liver disease (NAFLD), but it was not clear which exercise methods could effectively treat NAFLD. The purpose of this systematic review and meta-analysis was to evaluate the effects of different exercise patterns on eight indicators in patients with NAFLD. We searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data from its inception to 30 June 2020. This review includes all randomized controlled trials (RCT) that assessed and compared the effects of different exercise on eight indicator parameters in patients with NAFLD. The results indicate that aerobic exercises could significantly improve the eight indicators in patients with NAFLD including triglycerides (TG, weighted mean difference (WMD) = -0.53, 95%CI: -0.68~-0.39, Z = 7.37, < 0.01), total cholesterol (TC, WMD = -0.39, 95%CI: -0.55~-0.23, Z = 4.76, < 0.01), low density lipoprotein (LDL, WMD = -0.47, 95%CI: -0.68~-0.26, Z = 4.33, < 0.01), high density lipoprotein (HDL, WMD = 0.12, 95%CI: 0.05~0.18, Z = 3.56, < 0.01), alanine aminotransferase (ALT, WMD = -6.14, 95%CI: -10.99~-1.29, Z = 2.48, < 0.05), aspartate aminotransferase (AST, WMD = -5.73, 95%CI: -9.08~-2.38, Z = 3.36, < 0.01), and body mass index (BMI, WMD = -0.85, 95%CI: -1.19~-0.51, Z = 4.92, < 0.01). Resistance exercises could significantly reduce the levels of TG (WMD = -0.56, 95%CI: -0.85~-0.28, Z = 3.86, < 0.01) and AST (WMD = -2.58, 95%CI: -4.79~-0.36, Z = 2.28, < 0.05) in the patients. High-intensity interval training could significantly improve the level of ALT (WMD = -6.20, 95%CI: -9.34~-3.06, Z = 3.87, < 0.01) in patients with NAFLD. These three exercise methods had different effects on the eight indexes of NAFLD in our present meta-analysis, providing some reference for the establishment of exercise prescription for patients with NAFLD.
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http://dx.doi.org/10.3390/ijerph18063242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004001PMC
March 2021

Ag/Ultrathin-Layered Double Hydroxide Nanosheets Induced by a Self-Redox Strategy for Highly Selective CO Reduction.

ACS Appl Mater Interfaces 2021 Apr 1;13(14):16536-16544. Epub 2021 Apr 1.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.

The carbon-neutral photocatalytic CO reduction reaction (CORR) enables the conversion of CO into hydrocarbon fuels or value-added chemicals under mild conditions. Achieving high selectivity for the desired products of the CORR remains challenging. Herein, a self-redox strategy is developed to construct strong interfacial bonds between Ag nanoparticles and an ultrathin CoAl-layered double hydroxide (U-LDH) nanosheet support, where the surface hydroxyl groups associated with oxygen vacancies of U-LDH play a critical role in the formation of the interface structure. The supported Ag@U-LDH acts as a highly efficient catalyst for CO reduction, resulting in a high CO evolution rate of 757 μmol g h and a CO selectivity of 94.5% under light irradiation. Such a high catalytic selectivity may represent a new record among current photocatalytic CORR to CO systems. The Ag-O-Co interface bonding is confirmed by Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and FTIR CO adsorption studies. The in situ FTIR measurements indicate that the formation of the *COOH intermediate is accelerated and the mass transfer is improved during the CORR. Density functional theory calculations show that the Ag-O-Co interface reduces the formation energy of the *COOH intermediate and accumulates localized charge. Experimental and theoretical analysis collectively demonstrates that the strong interface bonding between Ag and U-LDH activates the interface structure as catalytically CORR active sites, effectively optimizing the binding energies with reacted intermediates and facilitating the CORR performance.
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http://dx.doi.org/10.1021/acsami.1c02737DOI Listing
April 2021

Disseminated Infection in a Non-HIV Infant With a Homozygous Private Variant of .

Front Cell Infect Microbiol 2021 15;11:605589. Epub 2021 Mar 15.

Department of Biochemistry, School of Basic Medical Science, Chengde Medical University, Chengde, China.

Objective: This study presents a relatively rare case of disseminated () infection in an HIV-negative patient.

Methods: An 8-month-old girl was hospitalized because of uncontrollable fever and cough for 6 days. Routine laboratory tests, biochemical detection, immunological tests, pathogenic examination, and imaging inspection were performed. Genetic tests of trio whole genome sequencing (Trio-WES), trio copy number sequencing (Trio-CNVseq), and Sanger sequencing were conducted to identify pathogenic variants. analysis of the sequence alignment and structural modeling results was carried out to study the possible pathogenicity of the identified variant. Western blotting was performed to investigate the expression of the identified gene at the protein level.

Results: Enhanced CT and MRI scanning demonstrated thymic dysplasia, diffuse pulmonary and liver nodules, and many balloon-like air sacs in both lungs. The white blood cell count, neutrophil count, and neutrophil ratio were normal or elevated. The patient was HIV-negative and bone marrow and blood culture showed infection. Total lymphocyte count, CD3+ T lymphocyte count, CD3+CD4+ T lymphocyte count, CD3+CD8+ T lymphocyte count, and NK cell count decreased, while the number of CD19 positive B cells increased. However, the ratio of CD3+CD4+:CD3+CD8+ T cells increased. Trio-WES identified a homozygous private variant of NM_006509: c.400_c.401insAGC/p.Lys134 delinsLysGln in and Sanger sequencing validated the result. Structural modeling indicated that the variant may be pathogenic. Reverse transcription-polymerase chain reaction and Western blot analysis showed that the expression of RelB in the patient was lower than that in the healthy controls at mRNA and protein levels.

Conclusion: This is the first report on disseminated infection in a patient with a homozygous private variant of .
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http://dx.doi.org/10.3389/fcimb.2021.605589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005656PMC
March 2021

Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence.

Nature 2021 Apr 31;592(7854):428-432. Epub 2021 Mar 31.

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we report that the stress hormone corticosterone-which is derived from the adrenal gland and is the rodent equivalent of cortisol in humans-regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice. In the absence of systemic corticosterone, HFSCs enter substantially more rounds of the regeneration cycle throughout life. Conversely, under chronic stress, increased levels of corticosterone prolong HFSC quiescence and maintain hair follicles in an extended resting phase. Mechanistically, corticosterone acts on the dermal papillae to suppress the expression of Gas6, a gene that encodes the secreted factor growth arrest specific 6. Restoring Gas6 expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Our work identifies corticosterone as a systemic inhibitor of HFSC activity through its effect on the niche, and demonstrates that the removal of such inhibition drives HFSCs into frequent regeneration cycles, with no observable defects in the long-term.
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http://dx.doi.org/10.1038/s41586-021-03417-2DOI Listing
April 2021

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages.

Gut Microbes 2021 Jan-Dec;13(1):1-23

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Human milk oligosaccharides (HMOs) and milk fat globule membrane (MFGM) are highly abundant in breast milk, and have been shown to exhibit potent immunomodulatory effects. Yet, their role in the gut microbiota modulation in relation to colitis remains understudied. Since the mixtures of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) perfectly mimic the properties and functions of HMOs, the combination of MFGM, FOS, and GOS (CMFG) has therefore been developed and used in this study. Here, CMFG were pre-fed to mice for three weeks to investigate its preventive effect on dextran sodium sulfate (DSS) induced colitis. Moreover, CMFG-treated and vehicle-treated mice were cohoused to further elucidate the preventive role of the gut microbiota transfer in colitis. At the end of the study, 16S rDNA gene amplicon sequencing, short-chain fatty acids (SCFAs) profiling, transcriptome sequencing, histological analysis, immunofluorescence staining and flow cytometry analysis were conducted. Our results showed that CMFG pre-supplementation alleviated DSS-induced colitis as evidenced by decreased disease activity index (DAI) score, reduced body weight loss, increased colon length and mucin secretion, and ameliorated intestinal damage. Moreover, CMFG reduced macrophages in the colon, resulting in decreased levels of IL-1β, IL-6, IL-8, TNF-α, and MPO in the colon and circulation. Furthermore, CMFG altered the gut microbiota composition and promoted SCFAs production in DSS-induced colitis. Markedly, the cohousing study revealed that transfer of gut microbiota from CMFG-treated mice largely improved the DSS-induced colitis as evidenced by reduced intestinal damage and decreased macrophages infiltration in the colon. Moreover, transfer of the gut microbiota from CMFG-treated mice protected against DSS-induced gut microbiota dysbiosis and promotes SCFAs production, which showed to be associated with colitis amelioration. Collectively, these findings demonstrate the beneficial role of CMFG in the gastrointestinal diseases, and further provide evidence for the rational design of effective prophylactic functional diets in both animals and humans.
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http://dx.doi.org/10.1080/19490976.2021.1903826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018355PMC
April 2021

A new species of (Anura, Ranidae) from Hunan Province, China.

Zookeys 2021 15;1024:91-115. Epub 2021 Mar 15.

Institute of Wildlife Conservation, Central South University of Forestry and Technology, Changsha 410004, China Central South University of Forestry and Technology Changsha China.

A new species, , is described, based on five specimens from Sangzhi County, Zhangjiajie City, Hunan Province, China. Molecular phylogenetic analyses, based on mitochondrial 12S rRNA and 16S rRNA gene sequences, strongly support the new species as a monophyletic group nested into the species complex. The new species can be distinguished from its congeners by a combination of the following characters: (1) body size medium (SVL: 42.1-45.1 mm in males, 83.3-92.7 mm in females); (2) dorsolateral folds absent; (3) tympanum diameter 1.53 times as long as the width of the disc of finger III in females; 2.3 times in males; (4) dorsal skin green with dense granules and sparse irregular brown spots; males with several large warts on dorsum; (5) two metacarpal tubercles; (6) relative finger lengths: I ≤ II < IV < III; (7) tibiotarsal articulation beyond the tip of the snout; (8) ventral surface smooth in females; throat and chest having pale spinules in adult males; (9) dorsal limbs green or yellow green with brown transverse bands; and (10) paired external vocal sacs located at corners of the throat, finger I with light yellow nuptial pad in males. This discovery increases the number of species to 59 and those known from China to 37.
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http://dx.doi.org/10.3897/zookeys.1024.56399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985132PMC
March 2021