Publications by authors named "Ting Wang"

3,742 Publications

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Elevated expression of the membrane-anchored serine protease TMPRSS11E in NSCLC progression.

Carcinogenesis 2022 Aug 11. Epub 2022 Aug 11.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Medicine School of Southeast University, Nanjing, 210009, China.

TMPRSS11E was found to be upregulated in human non-small cell lung cancer samples (NSCLC) and cell lines, and high expression was associated with poor survival of NSCLC patients. The results of in vitro and in vivo experiments showed that overexpressing TMPRSS11E resulted in A549 cell proliferation and migration promotion, while the TMPRSS11E S372A mutant with the mutated catalytic domain lost the promoting function. In addition, in mouse xenograft models, silencing TMPRSS11E expression inhibited the growth of 95D cell-derived tumors. To explore the mechanism of marked upregulation of TMPRSS11E in NSCLC cells, promoter analysis, EMSA and ChIP assays were performed. STAT3 was identified as the transcription factor responsible for TMPRSS11E transcription. Moreover, the purified recombinant TMPRSS11E catalytic domain exhibited enzymatic activity for the proteolytic cleavage of PAR2. Recombinant TMPRSS11E catalytic domain incubation further activated the PAR2-EGFR-STAT3 pathway. These findings established a mechanism of TMPRSS11E-PAR2-EGFR-STAT3 positive feedback, and the oncogenic role of TMPRSS11E as a PAR2 modulator in NSCLC was revealed.
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http://dx.doi.org/10.1093/carcin/bgac069DOI Listing
August 2022

Protective effect of apolipoprotein E epsilon 3 on sporadic Alzheimer's disease in the Chinese population: a meta-analysis.

Sci Rep 2022 Aug 10;12(1):13620. Epub 2022 Aug 10.

Department of Clinical Research Management, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.

Alzheimer's disease (AD) is fast becoming one of the most expensive, deadly and burdensome diseases in this century. It has the fastest-growing disease burden in China. Apolipoprotein E (APOE) polymorphic alleles are generally considered to be the primary genetic determinant of AD risk: individuals with the E4 allele are at increased risk of AD compared with individuals with the more common E3 allele. Since the intensity of the association varies among different ethnic groups, a separate meta-analysis of the Chinese population is needed. We searched Chinese and English databases to sift through literature over the past 20 years. Data on the APOE genotype and AD were collected for correlation analysis. OR was calculated according to APOE allele and genotype. A publication bias analysis and sensitivity analysis were performed, and the main results were further verified by subgroup analysis. The 116 eligible studies enrolled 23,396 patients with AD and 25,568 healthy controls. The study subjects covered at least 30 of the 34 provincial-level administrative regions (including Taiwan). The partial sex ratio was as follows: AD male/female; 10,291/11,240; control male/female, 11,304/12,428, [Formula: see text] = 0.122, P = 0.727. The results of the meta-analysis of alleles showed that I > 50% and Q statistics were significant for all genotypes; therefore, the random effect model was selected. The frequency of the ApoE ε4 allele in AD was higher than that in healthy controls, and the difference was statistically significant (OR 2.847, 95% CI [2.611-3.101], P < 0.001). The frequencies of ApoE ε3 and ε2 in AD were lower than those in healthy controls, and the differences were statistically significant (ε3: OR 0.539, 95% CI [0.504-0.576], P < 0.001; ε2: OR 0.771, 95% CI [0.705-0.843], P < 0.001). The results of the meta-analysis of AD genotype showed that ApoE ε2/ε4 (OR 1.521, 95% CI [1.270-1.823], P < 0.001), ε3/ε4 (OR 2.491, 95% CI [2.267-2.738], P < 0.001) and ε4/ε4 (OR 5.481, 95% CI [4.801-6.257], P < 0.001) allele genotype frequencies were higher than those of the healthy controls. The differences were all statistically significant. Moreover, the ApoE ε2/ε2 (OR 0.612, 95% CI [0.504-0.743], P < 0.001), ε2/ε3 (OR 0.649, 95% CI [0.585-0.714], P < 0.001) and ε3/ε3 (OR 0.508, 95% CI [0.468-0.551], P < 0.001) genotypes were less frequent in patients with AD than in healthy controls, and the differences were statistically significant. The results of the sensitivity analysis and subgroup analysis were consistent with those of the whole model. These results provide support for the protective effect of the ApoE ε3/ε3 genotype against the development of AD. This research is the most comprehensive meta-analysis of the correlation between APOE and AD in the Chinese population by analysing the distribution of the APOE gene in patients with AD reported in the last 20 years. It was concluded that the APOE ε3 allele had a protective effect against sporadic AD in the Chinese population, with great significance, and that its protective effect was stronger than that of the ε2 allele.
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http://dx.doi.org/10.1038/s41598-022-18033-xDOI Listing
August 2022

Semi-supervised classification of fundus images combined with CNN and GCN.

J Appl Clin Med Phys 2022 Aug 10:e13746. Epub 2022 Aug 10.

Shandong Key Laboratory of Medical Physics and Image Processing, Shandong Provincial Engineering and Technical Center of Light Manipulation, School of Physics and Electronics, Shandong Normal University, Jinan, China.

Purpose: Diabetic retinopathy (DR) is one of the most serious complications of diabetes, which is a kind of fundus lesion with specific changes. Early diagnosis of DR can effectively reduce the visual damage caused by DR. Due to the variety and different morphology of DR lesions, automatic classification of fundus images in mass screening can greatly save clinicians' diagnosis time. To alleviate these problems, in this paper, we propose a novel framework-graph attentional convolutional neural network (GACNN).

Methods And Materials: The network consists of convolutional neural network (CNN) and graph convolutional network (GCN). The global and spatial features of fundus images are extracted by using CNN and GCN, and attention mechanism is introduced to enhance the adaptability of GCN to topology map. We adopt semi-supervised method for classification, which greatly improves the generalization ability of the network.

Results: In order to verify the effectiveness of the network, we conducted comparative experiments and ablation experiments. We use confusion matrix, precision, recall, kappa score, and accuracy as evaluation indexes. With the increase of the labeling rates, the classification accuracy is higher. Particularly, when the labeling rate is set to 100%, the classification accuracy of GACNN reaches 93.35%. Compared with DenseNet121, the accuracy rate is improved by 6.24%.

Conclusions: Semi-supervised classification based on attention mechanism can effectively improve the classification performance of the model, and attain preferable results in classification indexes such as accuracy and recall. GACNN provides a feasible classification scheme for fundus images, which effectively reduces the screening human resources.
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http://dx.doi.org/10.1002/acm2.13746DOI Listing
August 2022

PNGase H+ variant from Rudaea cellulosilytica with improved deglycosylation efficiency for rapid analysis of eukaryotic N-glycans and HDX-MS analysis of glycoproteins.

Rapid Commun Mass Spectrom 2022 Aug 9:e9376. Epub 2022 Aug 9.

Glycomics and Glycan Bioengineering Research Center (GGBRC), College of Food Science and Technology, Nanjing Agricultural University, China.

The analysis of glycoproteins and the comparison of protein N-glycosylation from different eukaryotic origins requires unbiased and robust analytical workflows. The structural and functional analysis of vertebrate protein N-glycosylation currently depends extensively on bacterial Peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidases (PNGases), which are indispensable enzymatic tools in releasing asparagine-linked oligosaccharides (N-glycans) from glycoproteins. So far, only limited PNGase candidates are available for N-glycans analysis, and particularly the analysis of plant and invertebrate N-glycans is hampered by the lack of suitable PNGases. Furthermore, LC-MS workflows such as hydrogen deuterium exchange mass spectrometry (HDX-MS) require a highly efficient enzymatic release of N-glycans at low pH to facilitate the comprehensive structural analysis of glycoproteins. Herein, we describe a previously unstudied superacidic bacterial N-glycanase (PNGase H ) originating from the soil bacterium Rudaea cellulosilytica (Rc), which has significantly improved enzymatic properties compared to previously described PNGase H variants. Active and soluble recombinant PNGase Rc was be expressed at a higher protein level (3.8-fold) and with higher specific activity (~56% increase) compared to the currently used PNGase H variant from Dyella japonicum (Dj). Recombinant PNGase Rc was able to deglycosylate the glycoproteins horseradish peroxidase and bovine lactoferrin significantly faster compared to PNGase Dj (10 min versus 6 hrs). The versatility of PNGase Rc was demonstrated by releasing N-glycans from a diverse array of samples such as peach fruit, king trumpet mushroom, mouse serum, and the soil nematode Caenorhabditis elegans. The presence of only two disulfide bonds shown in the AlphaFold protein model (so far all other superacidic PNGases possess more disulfide bonds) could be corroborated by intact mass - and peptide mapping analysis and provides a possible explanation for the improved recombinant expression yield of PNGase Rc.
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http://dx.doi.org/10.1002/rcm.9376DOI Listing
August 2022

Development, Characterization and Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2.

Front Bioeng Biotechnol 2022 22;10:920696. Epub 2022 Jul 22.

Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam, Netherlands.

The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the osteoinductive efficacy in a subcutaneous bone induction model in rats. characterization data showed that the BpNcCaP + BMP-2 granules were comprised of hexagonal hydroxyapatite with an average crystallite size ranging from 19.7 to 25.1 nm and a grain size at 84.13 ± 28.46 nm. The vickers hardness of BpNcCaP was 32.50 ± 3.58 HV 0.025. BpNcCaP showed no obvious cytotoxicity and was favorable for the adhesion of pre-osteoblasts. BMP-2 incorporation rate could be as high as 65.04 ± 6.01%. histomorphometric analysis showed that the volume of new bone induced by BpNcCaP exhibited a BMP-2 amount-dependent increasing manner. The BpNcCaP+50 μg BMP-2 exhibited significantly more degradation and fewer foreign body giant cells in comparison with BpNcCaP. These data suggested a promising application potential of BpNcCaP + BMP-2 in repairing LVBDs.
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http://dx.doi.org/10.3389/fbioe.2022.920696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354744PMC
July 2022

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors the Inhibition of Inflammation Mediated by Nitric Oxide Synthase.

Front Pharmacol 2022 19;13:920201. Epub 2022 Jul 19.

Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine nitroglycerin (NTG) injection. The experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1β, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). , XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.
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http://dx.doi.org/10.3389/fphar.2022.920201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344691PMC
July 2022

Clinical and molecular cytogenetic findings and pregnancy outcomes of fetuses with isochromosome Y.

Mol Cytogenet 2022 Aug 4;15(1):32. Epub 2022 Aug 4.

Prenatal Diagnosis Centre, Guangdong Women and Children Hospital, 521-523 Xingnan Road, Guangzhou, 511442, Guangdong, China.

Background: The mosaic forms and clinical phenotypes of fetuses with isochromosome Y are difficult to predict. Therefore, we summarized the cases of nine fetuses with isochromosome Y identified in prenatal diagnosis with a combination of molecular cytogenetic techniques, providing clinical evidence for prenatal genetic counseling.

Methods: The prenatal diagnosis and pregnancy outcomes of nine fetuses with isochromosome Y were obtained by a  retrospective analysis. Isochromosome Y was identified prenatally by different approaches, such as conventional karyotyping, chromosomal microarray analysis (CMA), quantitative fluorescent polymerase chain reaction (QF-PCR) and fluorescence in situ hybridization (FISH).

Results: Seven idic(Y) fetuses and two i(Y) fetuses were identified. One fetus was complete for i(Y)(p10), and the rest with 45,X had mosaic forms. A break and fusion locus was identified in Yp11.3 in one fetus, in Yq11.22 in six fetuses and in Yp10 in two fetuses. The CMA results suggested that different deletions and duplications were found on the Y chromosome. The deletion fragments ranged from 4.7 Mb to the entire Y chromosome, and the duplication fragments ranged from 10.4 to 18.0 Mb. QF-PCR analysis suggested that the AZF region was intact in one fetus, four fetuses had AZFb+c+d deletion, one fetus had AZFa+b+c+d deletion, and one fetus had AZFc+d deletion. Finally, four healthy male neonates were delivered successfully, but the parents of the remaining five fetuses, including three healthy and two unhealthy fetuses, chose to terminate their pregnancies.

Conclusion: The fetus and neonate phenotype of prenatally detected isochromosome Y usually is that of a normally developed male, ascertained in the absence of other indicators of a fetal structural anomaly. Our study provides clinical reference materials for risk assessment and permits better prenatally counseling and preparation of parents facing the birth of isochromosome Y fetuses.
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http://dx.doi.org/10.1186/s13039-022-00611-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351221PMC
August 2022

Development and validation of a noninvasive prediction model for identifying eosinophilic asthma.

Respir Med 2022 Jul 19;201:106935. Epub 2022 Jul 19.

Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, PR China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, PR China. Electronic address:

Background: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA).

Methods: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated.

Results: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/).

Conclusion: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.
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http://dx.doi.org/10.1016/j.rmed.2022.106935DOI Listing
July 2022

Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis.

Clin Rheumatol 2022 Aug 4. Epub 2022 Aug 4.

Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, 212001, China.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA.

Methods: A total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4, CD19 B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( -) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA).

Results: Patients with RA had higher percentages of CD4 T, CD19 B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF or ACPA patients exhibited elevated percentages of CD19 B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF/ACPA and RF/ACPA patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different.

Conclusion: Th17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA. Key Points • Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages. • No difference for the distribution of Th17, Treg, and ILC subsets between RF and RF patients and between ACPA and ACPA patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.
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http://dx.doi.org/10.1007/s10067-022-06315-8DOI Listing
August 2022

Challenges and Opportunities for Companies to Build HTA/Payer Perspectives Into Drug Development Through the Use of a Dynamic Target Product Profile.

Front Pharmacol 2022 18;13:948161. Epub 2022 Jul 18.

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.

The target product profile (TPP) outlines the desired profile of a target product aimed at a particular disease and is used by companies to plan clinical development. Considering the increasing importance of health technology assessment (HTA) in informing reimbursement decisions, a robust TPP needs to be built to address HTA needs, to guide an integrated evidence generation plan that will support HTA submissions. This study assessed current practices and experiences of companies in building HTA considerations into TPP development. An opinion survey was designed and conducted in 2019, as a cross-sectional questionnaire consisting of multiple-choice questions. The questionnaire provided a qualitative assessment of companies' strategies and experiences in building HTA considerations into the TPP. Eligible survey participants were the senior management of Global HTA/Market Access Departments at 18 top international pharmaceutical companies. 11 companies responded to the survey. All companies included HTA requirements in TPP development, but the timing and process varied. The key focus of HTA input related to health problems and treatment pathways, clinical efficacy/effectiveness, and safety. Variance of HTA methods and different value frameworks were identified as a challenge for development plans. Stakeholder engagement, such as HTA scientific advice, was used to pressure test the TPP. This research provides insight into current practice and potential opportunities for value-based drug development. It demonstrates the evolution of the TPP to encompass HTA requirements and suggests that the TPP could have a role as an iterative communication tool for use with HTA agencies to enhance an integrated evidence generation plan.
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http://dx.doi.org/10.3389/fphar.2022.948161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340272PMC
July 2022

Emerging investigator series: metal nanoparticles in freshwater: transformation, bioavailability and effects on invertebrates.

Authors:
Ting Wang Wei Liu

Environ Sci Nano 2022 Jul 6;9(7):2237-2263. Epub 2022 May 6.

Department F.-A. Forel for Environmental and Aquatic Sciences, Faculty of Sciences, Earth and Environment Sciences, University of Geneva Uni Carl Vogt, 66 Blvd Carl-Vogt CH 1211 Geneva Switzerland

The increasing use of metal oxide-based nanoparticles (MNPs) and their release into the environment cast concerns about their environmental impacts. Massive efforts have been focused on environmental behaviours and ecotoxicities to figure out the potential threats posed by MNPs. This review systematically summarises and re-analyses published data about the MNP interactions and transformation processes in freshwater and the toxicological effects of MNPs on invertebrates. A case study was conducted through meta-analysis to examine the impacts of silver nanoparticle exposure to freshwater invertebrates. The conclusions categorized the current understanding of the outcome and ecotoxicity of MNPs in freshwater. The adverse outcome pathway (AOP) is recommended for environmental risk assessment as it provides a rapid and accurate risk assessment of an increasing number of novel compounds consuming fewer resources and animal tests. Invertebrates contribute significantly towards developing robust AOPs thanks to a shorter life cycle, allowing chronic and complete life cycle toxicity tests.
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http://dx.doi.org/10.1039/d2en00052kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282172PMC
July 2022

A fetal fraction enrichment method reduces false negatives and increases test success rate of fetal chromosome aneuploidy detection in early pregnancy loss.

J Transl Med 2022 08 2;20(1):345. Epub 2022 Aug 2.

Center for Reproduction and Genetics, School of Gusu, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, Jiangsu Province, China.

Objective: We and others have previously demonstrated that the size-selection enrichment method could remarkably improve fetal fraction (FF) in the early gestational age (GA, 12-13 weeks), suggesting that 9 or 10 weeks should not be used as a threshold for GA in size-selection noninvasive prenatal screening (NIPS). Here, we assessed whether this method was reliable for detecting fetal chromosomal aneuploidy at the earliest GA (6-8 weeks).

Methods: Size-selection NIPS for fetal chromosomal aneuploidy was applied to 208 pregnancy plasma samples (102 male and 106 female fetuses), while the 169 pregnancy samples with male fetuses also underwent standard NIPS. Multivariable linear regression models were used to evaluate the association between fold-change of FF and experimental factors.

Results: The sensitivity of the cell-free DNA (cfDNA) test in detecting aneuploidy was 100% when screened with FF enrichment, whereas the sensitivity of the same patients was only 62.5% (5/8) without FF enrichment. In the 102 pregnancy samples with male fetuses, FF increased from 6.1% to 15.7%, and the median increase in FF was 2.8-fold with enrichment. Moreover, there was a trend toward an increasing success rate of the cfDNA test from 6 to 13 weeks of gestation, especially when the test success rate reached 100% after 7 weeks with FF enrichment. Multivariate linear regression analysis demonstrated that a lower initial FF, shorter cfDNA size, increased body mass index (BMI), and later GA were all independent predictors of a higher fold-change of FF. Compared with ≤ 120 bp cfDNA fragments, the mean fold-change of FF differences was 0.820 for 121-125 bp, 0.229 for 126-130 bp, - 0.154 for 131-135 bp, - 0.525 for 136-140 bp and - 0.934 for > 140 bp (P < 0.0001), suggesting that fold-change of FF significantly decreased with cfDNA fragments > 125 bp. These results were statistically significant after adjusting for confounding factors in the models for fold-change of FF.

Conclusions: The FF enrichment method is a reasonable strategy to detect fetal chromosomal aneuploidy in early pregnancy loss with reduced false negatives and increased test success rate after 7 weeks of GA and should be recommended for patients with early pregnancy loss.
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http://dx.doi.org/10.1186/s12967-022-03555-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344718PMC
August 2022

An Equivalent Substitute Strategy for Constructing 3D Ordered Porous Carbon Foams and Their Electromagnetic Attenuation Mechanism.

Nanomicro Lett 2022 Aug 2;14(1):157. Epub 2022 Aug 2.

College of Materials Science and Engineering, College of Electromechanical Engineering, Qingdao University of Science and Technology, Qingdao, 266061, People's Republic of China.

Three-dimensional (3D) ordered porous carbon is generally believed to be a promising electromagnetic wave (EMW) absorbing material. However, most research works targeted performance improvement of 3D ordered porous carbon, and the specific attenuation mechanism is still ambiguous. Therefore, in this work, a novel ultra-light egg-derived porous carbon foam (EDCF) structure has been successfully constructed by a simple carbonization combined with the silica microsphere template-etching process. Based on an equivalent substitute strategy, the influence of pore volume and specific surface area on the electromagnetic parameters and EMW absorption properties of the EDCF products was confirmed respectively by adjusting the addition content and diameter of silica microspheres. As a primary attenuation mode, the dielectric loss originates from the comprehensive effect of conduction loss and polarization loss in S-band and C band, and the value is dominated by polarization loss in X band and Ku band, which is obviously greater than that of conduction loss. Furthermore, in all samples, the largest effective absorption bandwidth of EDCF-3 is 7.12 GHz under the thickness of 2.13 mm with the filling content of approximately 5 wt%, covering the whole Ku band. Meanwhile, the EDCF-7 sample with optimized pore volume and specific surface area achieves minimum reflection loss (RL) of - 58.08 dB at 16.86 GHz while the thickness is 1.27 mm. The outstanding research results not only provide a novel insight into enhancement of EMW absorption properties but also clarify the dominant dissipation mechanism for the porous carbon-based absorber from the perspective of objective experiments.
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http://dx.doi.org/10.1007/s40820-022-00900-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346049PMC
August 2022

Spatial-temporal-demographic and virological changes of hand, foot and mouth disease incidence after vaccination in a vulnerable region of China.

BMC Public Health 2022 08 1;22(1):1468. Epub 2022 Aug 1.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China.

Background: The enterovirus 71 (EV-A71) vaccine has been used in Hefei for several years, and the epidemiological significance of vaccination in this area is unclear. We aims to explore the spatial-temporal-demographic and virological changes of hand, foot and mouth disease (HFMD) after vaccination in China.

Methods: The data for HFMD from 2012 to 2020 were downloaded with the help of HFMD reporting system of Hefei Center for Disease Control and Prevention and combined with the EV-A71 vaccination status in Hefei. The study defined the period between 2012 to 2016 as the pre-vaccination period and explored the effect of vaccination on the incidence of HFMD by comparing the changes of HFMD before and after vaccination in terms of spatial, temporal, demographic and virological aspects.

Results: During the study period, a higher incidence occurred in urban area and the random distribution changed to a slight cluster after vaccination. HFMD incidence had inconsistent seasonality over years, with one or two incidence peaks in varying years. The morbidity decreased from 215.22/105 in 2012-2016 to 179.81/105 in 2017-2020 (p < 0.001). Boys, 0-4 years old children and Scattered children were more susceptible to HFMD compared with the others, the proportions decreased after vaccination except in Scattered children. The main pathogenic enterovirus gradually changed from EV-A71 to Other Enteroviruses, especially coxsackieviruses A6 (CV-A6) after the implementation of EV-A71 vaccination.

Conclusions: The EV-A71 vaccine was effective in reducing the incidence of HFMD and changing the spatial, temporal, demographic, and virological characteristic. These changes should be considered during the vaccination implementation to further reduce the disease burden of HFMD.
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http://dx.doi.org/10.1186/s12889-022-13860-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342842PMC
August 2022

Single-mode lasing in an AlGaInAs/InP dual-port square microresonator.

Opt Lett 2022 Aug;47(15):3672-3675

Mode selection is crucial to achieving stable single-mode lasing in microlasers. Here, we demonstrate experimentally a dual-port square microresonator for single-mode lasing with a side-mode-suppression ratio (SMSR) exceeding 40 dB. By connecting waveguides at two opposite vertices, the quality factor for the antisymmetric mode (ASM) is much higher than that of the symmetric mode (SM), enabling single-mode lasing. Furthermore, far-field interference patterns similar to Young's two-slit interference are observed. This microlaser is capable of providing two optical sources simultaneously for optical signal processing in high-density integrated photonic circuits.
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http://dx.doi.org/10.1364/OL.461304DOI Listing
August 2022

Construction of a Nomogram Discriminating Malignancy-Associated Membranous Nephropathy From Idiopathic Membranous Nephropathy: A Retrospective Study.

Front Oncol 2022 14;12:914092. Epub 2022 Jul 14.

Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Based on the etiology, membranous nephropathy (MN) can be categorized into idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy. Malignancy-associated membranous nephropathy (MMN) is a common type of secondary MN. Its incidence is only second to that of lupus nephritis. As the treatment and prognosis of MMN differ significantly from those of other MNs, the identification of MMN is crucial for clinical practice. The purpose of this study was to develop a model that could efficiently discriminate MMN, to guide more precise selection of therapeutic strategies.

Methods: A total of 385 with IMN and 62 patients with MMN, who were hospitalized at the First Affiliated Hospital of Zhengzhou University between January 2017 and December 2020 were included in this study. We constructed a discriminant model based on demographic information and laboratory parameters for distinguishing MMN and IMN. To avoid an increased false positivity rate resulting from the large difference in sample numbers between the two groups, we matched MMN and IMN in a 1:3 ratio according to gender. Regression analysis was subsequently performed and a discriminant model was constructed. The calibration ability and clinical utility of the model were assessed calibration curve and decision curve analysis.

Results: We constructed a discriminant model based on age, CD4 T cell counts, levels of cystatin C, albumin, free triiodothyronine and body mass index, with a diagnostic power of 0.860 and 0.870 in the training and test groups, respectively. The model was validated to demonstrate good calibration capability and clinical utility.

Conclusion: In clinical practice, patients demonstrating higher scores after screening with this model should be carefully monitored for the presence of tumors in order to improve their outcome.
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http://dx.doi.org/10.3389/fonc.2022.914092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329587PMC
July 2022

Nakai-Induced Liver Injury-A Mechanistic Study Using Untargeted Metabolomics.

Front Pharmacol 2022 13;13:934057. Epub 2022 Jul 13.

Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Epimedii Folium is widely used worldwide as an herbal supplement, and the risk of its induced liver damage has emerged in recent years. Our preliminary study has found that, among several Epimedii Folium species specified in the Chinese Pharmacopoeia, Nakai has a more severe propensity for hepatotoxicity. However, the mechanism of hepatotoxicity of Nakai is still unclear. In this study, untargeted metabolomics was performed to analyze the serum and liver tissue to explore the mechanism of hepatotoxicity of Nakai. The results of experiments showed that, after 28 days of exposure to Nakai ethanol extract (EEE), the liver weight, levels of AST, ALP, TBIL, etc. in serum of rats in the EEE group were significantly increased, as well as severe cytoplasmic vacuolation appeared in the liver tissue, which suggested that EEE has significant hepatotoxicity. Subsequently, the results of metabolomics revealed significant changes in the metabolic profile in the liver and serum of rats after EEE exposure, in which metabolites in serum such as flavin mononucleotide, phenylacetylglycine, glutathione, l-tryptophan, and sphingomyelin were able to accurately identify liver injury caused by EEE and could be used as serum markers to reflect EEE-induced liver injury. The KEGG pathway enrichment analysis revealed that EEE caused extensive effects on rats' metabolic pathways. Some of the most affected pathways included glutathione metabolism, glutamate metabolism pathway, primary bile acid biosynthesis pathway, and sphingolipid metabolism pathway, which were all directed to the biological process of ferroptosis. Then, the main markers related to ferroptosis in the liver were examined, and the results demonstrated that the content of malondialdehyde was significantly increased, the activity of superoxide dismutase was significantly reduced, the ferroptosis inhibitory proteins GPX4 and System x were significantly downregulated, and the ferroptosis-promoting protein ACSL4 was significantly up-regulated. Judging from these results, we concluded that the mechanism of hepatotoxicity of Nakai was probably related to the induction of ferroptosis in hepatocytes.
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http://dx.doi.org/10.3389/fphar.2022.934057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326364PMC
July 2022

Rh(III)-Catalyzed chemo-, regio- and stereoselective carboamination of sulfonyl allenes with -phenoxy amides or -enoxy imides.

Chem Commun (Camb) 2022 Jul 29. Epub 2022 Jul 29.

Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, P. R. China.

The Rh(III)-catalyzed chemo-, regio- and stereoselective carboamination of sulfonyl allenes has been realized by virtue of either -phenoxy amides or -enoxy imides simultaneously acting as the C- and N-sources, redox-neutral tandem C-H activation/allene insertion/oxidative addition/C-N bond formation for the direct construction of allylamine derivatives equipped with an α-quaternary carbon center. This protocol features high atom-economy with good substrate compatibility and exhibits profound synthetic potential for late-stage C-H modification of complex molecules.
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http://dx.doi.org/10.1039/d2cc02982kDOI Listing
July 2022

Cardiomyocytes induced from hiPSCs by well-defined compounds have therapeutic potential in heart failure by secreting PDGF-BB.

Signal Transduct Target Ther 2022 Jul 29;7(1):253. Epub 2022 Jul 29.

School of Life Science, Beijing University of Chinese Medicine, Beijing, China.

Recent studies have suggested that transplant of hiPS-CMs is a promising approach for treating heart failure. However, the optimally clinical benefits have been hampered by the immature nature of the hiPS-CMs, and the hiPS-CMs-secreted proteins contributing to the repair of cardiomyocytes remain largely unidentified. Here, we established a saponin compound optimally induced system to generate hiPS-CMs with stable functional attributes in vitro and transplanted in heart failure mice. Our study showed enhanced therapeutic effects of optimally induced hiPS-CMs by attenuating cardiac remodeling and dysfunction, these beneficial effects were concomitant with reduced cardiomyocytes death and increased angiogenesis. Moreover, the optimally induced hiPS-CMs could gathering to the injured heart and secret an abundant PDGF-BB. The reparative effect of the optimally induced hiPS-CMs in the hypoxia-injured HCMs was mimicked by PDGF-BB but inhibited by PDGF-BB neutralizing antibody, which was accompanied by the changed expression of p-PI3K and p-Akt proteins. It is highly possible that the PI3K/Akt pathway is regulated by the PDGF-BB secreted from the compound induced hiPS-CMs to achieve a longer lasting myocardial repair effect compared with the standard induced hiPS-CMs. Taken together, our data strongly implicate that the compound induced hiPS-CMs promote the recovery of injured hearts via paracrine action. In this process, the paracrine factor PDGF-BB derived from the compound induced hiPS-CMs reduces isoproterenol-induced adverse cardiac remodeling, which is associated with improved cardiac function, and these effects are mediated by the PI3K/Akt pathway, suggesting that the optimally induced hiPS-CMs may serve as a new promising cell therapy for clinical applications.
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http://dx.doi.org/10.1038/s41392-022-01045-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334380PMC
July 2022

Family Physician Income Disparities by Race and Gender.

J Am Board Fam Med 2022 Jul-Aug;35(4):859-861

From The GW School of Medicine and Health Sciences, Washington, DC (AA); American Board of Family Medicine, Lexington, KY (ZJM, RHO, AB, MKT, TW, ARE); The Robert Graham Center, Washington, DC (RHO).

A race and gender salary gap has been well-documented throughout the U.S. economy, but little described in primary care. Using self-reported data on the most widely distributed primary care physician specialty, we reveal lower incomes and hourly wages among Black/African American and female family physicians. The clear gradient in family physician compensation by race and gender demands further study and action to better understand and address the underlying sources of these differences.
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http://dx.doi.org/10.3122/jabfm.2022.04.210472DOI Listing
July 2022

Breast cancer-related lymphoedema and resistance exercise: An evidence-based review of guidelines, consensus statements and systematic reviews.

J Clin Nurs 2022 Jul 27. Epub 2022 Jul 27.

School of Nursing, Peking University, Beijing, China.

Aims And Objectives: Breast cancer-related lymphoedema (BCRL) is a side effect of cancer treatment and can be alleviated by resistance exercise. This systematic, evidence-based review examined the existing best evidence on resistance exercise for BCRL to accurately describe the current status of the field and offer recommendations for clinicians.

Methods: This review adheres to the PRISMA guidelines. Clinical practice guidelines, consensus documents, systematic reviews and other related evidence-based resources about resistance exercise for BCRL were retrieved through the English databases and guideline websites. The publication data limit was set to December 2020. The following search terms were used: 'breast cancer/breast neoplasm/breast carcinoma/breast tumor/breast malignancy, lymphedema/swelling/edema/lymphoedema, resistance/weight/strength training, best practice/clinical practice/guideline/consensus documents'. The quality of the included studies was evaluated by two authors independently using AGREE II and AMSTAR II tools. Evidence-based recommendations on resistance exercise relevant for BCRL were synthesised and categorised.

Results: Twenty two articles (seven guidelines, four consensus documents and eleven systematic reviews) were included. The overall quality of the eleven eligible guidelines and consensus documents was moderate to high according to the AGREE II criteria. The quality of the eleven systematic reviews was critically low to high according to the AMSTAR criteria. Six clinical topics involving 43 recommendations were identified. Recommendations were categorised by safety of resistance training, effectiveness of resistance training, evaluation prior to resistance exercise, resistance exercise prescription, resistance training outcome index and points for attention.

Conclusions: This study summarises 43 recommendations for resistance training for BCRL and provides guidance for clinicians. Based on randomised trials and systematic reviews published in recent years, there is an urgent need to update the guidelines and consensus documents in terms of topics, for example effectiveness of resistance training and resistance training outcome index.
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http://dx.doi.org/10.1111/jocn.16437DOI Listing
July 2022

EEG-Based Emotion Classification Using Improved Cross-Connected Convolutional Neural Network.

Brain Sci 2022 Jul 24;12(8). Epub 2022 Jul 24.

Key Laboratory of Brain Machine Collaborative Intelligence of Zhejiang Province, Hangzhou 310018, China.

The use of electroencephalography to recognize human emotions is a key technology for advancing human-computer interactions. This study proposes an improved deep convolutional neural network model for emotion classification using a non-end-to-end training method that combines bottom-, middle-, and top-layer convolution features. Four sets of experiments using 4500 samples were conducted to verify model performance. Simultaneously, feature visualization technology was used to extract the three-layer features obtained by the model, and a scatterplot analysis was performed. The proposed model achieved a very high accuracy of 93.7%, and the extracted features exhibited the best separability among the tested models. We found that adding redundant layers did not improve model performance, and removing the data of specific channels did not significantly reduce the classification effect of the model. These results indicate that the proposed model allows for emotion recognition with a higher accuracy and speed than the previously reported models. We believe that our approach can be implemented in various applications that require the quick and accurate identification of human emotions.
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http://dx.doi.org/10.3390/brainsci12080977DOI Listing
July 2022

Recent Progress on Bioinspired Antibacterial Surfaces for Biomedical Application.

Biomimetics (Basel) 2022 Jul 4;7(3). Epub 2022 Jul 4.

Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong 999077, China.

Surface bacterial fouling has become an urgent global challenge that calls for resilient solutions. Despite the effectiveness in combating bacterial invasion, antibiotics are susceptible to causing microbial antibiotic resistance that threatens human health and compromises the medication efficacy. In nature, many organisms have evolved a myriad of surfaces with specific physicochemical properties to combat bacteria in diverse environments, providing important inspirations for implementing bioinspired approaches. This review highlights representative natural antibacterial surfaces and discusses their corresponding mechanisms, including repelling adherent bacteria through tailoring surface wettability and mechanically killing bacteria via engineering surface textures. Following this, we present the recent progress in bioinspired active and passive antibacterial strategies. Finally, the biomedical applications and the prospects of these antibacterial surfaces are discussed.
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http://dx.doi.org/10.3390/biomimetics7030088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326651PMC
July 2022

Avian IRF1 and IRF7 Play Overlapping and Distinct Roles in Regulating IFN-Dependent and -Independent Antiviral Responses to Duck Tembusu Virus Infection.

Viruses 2022 07 9;14(7). Epub 2022 Jul 9.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Avian interferon regulatory factors 1 and 7 (IRF1 and IRF7) play important roles in the host's innate immunity against viral infection. Our previous study revealed that duck tembusu virus (DTMUV) infection of chicken fibroblasts (DF1) and duck embryo fibroblasts (DEFs) induced the expression of a variety of IFN-stimulated genes (ISGs), including VIPERIN, IFIT5, CMPK2, IRF1, and IRF7. IRF1 was further shown to play a significant role in regulating the up-expression of VIPERIN, IFIT5, and CMPK2 and inhibiting DTMUV replication. In this study, we confirm, through overexpression and knockout approaches, that both IRF1 and IRF7 inhibit DTMUV replication, mainly via regulation of type I IFN expression, as well as the induction of IRF1, VIPERIN, IFIT5, CMPK2, and MX1. In addition, IRF1 directly promoted the expression of VIPERIN and CMPK2 in an IFN-independent manner when IRF7 and type I IFN signaling were undermined. We also found that non-structural protein 2B (NS2B) of DTMUV was able to inhibit the induction of IFN-β mRNA triggered by Newcastle disease virus (NDV) infection or poly(I:C) treatment, revealing a strategy employed by DTMUV to evade host's immunosurveillance. This study demonstrates that avian IRF7 and IRF1 play distinct roles in the regulation of type I IFN response during DTMUV infection.
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http://dx.doi.org/10.3390/v14071506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315619PMC
July 2022

A Non-Cell-Autonomous Mode of DNA Damage Response in Soma of .

Int J Mol Sci 2022 Jul 7;23(14). Epub 2022 Jul 7.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Life has evolved a mechanism called DNA damage response (DDR) to sense, signal and remove/repair DNA damage, and its deficiency and dysfunction usually lead to genomic instability and development of cancer. The signaling mode of the DDR has been believed to be of cell-autonomy. However, the paradigm is being shifted with in-depth research into model organism . Here, we mainly investigate the effect of DDR activation on the radiosensitivity of vulva of , and first found that the vulval radiosensitivity is mainly regulated by somatic DDR, rather than the DDR of germline. Subsequently, the worm lines with pharynx-specific rescue of DDR were constructed, and it is shown that the 9-1-1-ATR and MRN-ATM cascades in pharynx restore approximately 90% and 70% of vulval radiosensitivity, respectively, through distantly regulating the NHEJ repair of vulval cells. The results suggest that the signaling cascade of DDR might also operate in a non-cell autonomous mode. To further explore the underlying regulatory mechanisms, the mutated gene is introduced into the DDR-rescued worms, and CPR-4, a cysteine protease cathepsin B, is confirmed to mediate the inter-tissue and inter-individual regulation of DDR as a signaling molecule downstream of 9-1-1-ATR. Our findings throw some light on the regulation of DNA repair in soma of , and might also provide new cues for cancer prevention and treatment.
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http://dx.doi.org/10.3390/ijms23147544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318560PMC
July 2022

Estimating the Carbon Emission of Construction Waste Recycling Using Grey Model and Life Cycle Assessment: A Case Study of Shanghai.

Int J Environ Res Public Health 2022 Jul 12;19(14). Epub 2022 Jul 12.

Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guizhou 550001, China.

Great efforts have been exerted in reducing carbon emissions in design, construction and operation stages. However, little attention is paid to the quantification of carbon emissions in construction waste recycling at the end-of-life stage. This study aims to quantitatively analyze the carbon emission of construction waste in Shanghai City, PR China. A grey model is used to forecast the generation amount of construction waste, and a life cycle assessment is performed to estimate the carbon emission of construction waste. In this study, both the carbon emission of recycling activities (environmental costs), and the equivalent amount of carbon generated from alternative materials (environmental benefit) are considered. Here, recycling 1 ton (t) of construction waste in Shanghai can save 100.4 kg CO-e. The total carbon-emission-saving potential can be increased from 0.31 million t CO-e (2022) to 0.35 million t CO-e (2031). The carbon emission of recycling concrete, brick, steel, wood and mortar, identified as the key components of construction waste, is investigated. This research can help to reduce carbon emissions and further achieve carbon neutrality for Shanghai City. The proposed methods can also be applied to other regions, especially when the data for construction waste are insufficient.
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http://dx.doi.org/10.3390/ijerph19148507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323168PMC
July 2022

The Complete Mitochondrial Genome of L. Is with Highly Repetitive Sequences: Intergenomic Fragment Transfer and Phylogenetic Analysis.

Genes (Basel) 2022 Jul 21;13(7). Epub 2022 Jul 21.

College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.

Many plant mitochondrial (mt) genomes have been sequenced but few in ferns. represents a typical species of fern genus with medicinal and scientific value. However, its mt genome structure remains to be characterized. This study assembled and annotated the complete mt genome and presented its structural characters and repeat sequences firstly. Its mt and chloroplast (cp) transfer sequences were explored, and the phylogenetic significance of both mt and cp genomes was also evaluated at the family level. Our results showed that the complete mt genome of is a single circular genome of 369,673 bp in length, containing 5000 dispersed repetitive sequences. Phylogenetic trees reconstructed from cp and mt genomes displayed similar topologies, but also showed subtle differences at certain nodes. There exist 4818 bp common gene fragments between cp and mt genomes, of which more than 70% are located in tRNA intergenic regions (in mt). In conclusion, we assembled the complete mt genome of , identified its remarkable structural characters, and provided new insights on ferns. The complementary results derived from mt and cp phylogeny highlighted that some higher taxonomic-level phylogenetic relationships among ferns remain to be resolved.
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http://dx.doi.org/10.3390/genes13071287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316493PMC
July 2022

Plastid Phylogenomics and Plastomic Diversity of the Extant Lycophytes.

Genes (Basel) 2022 Jul 19;13(7). Epub 2022 Jul 19.

Shenzhen Key Laboratory for Orchid Conservation and Utilization, National Orchid Conservation Center of China and the Orchid Conservation & Research Center of Shenzhen, Shenzhen 518114, China.

Although extant lycophytes represent the most ancient surviving lineage of early vascular plants, their plastomic diversity has long been neglected. The ancient evolutionary history and distinct genetic diversity patterns of the three lycophyte families, each with its own characteristics, provide an ideal opportunity to investigate the interfamilial relationships of lycophytes and their associated patterns of evolution. To compensate for the lack of data on Lycopodiaceae, we sequenced and assembled 14 new plastid genomes (plastomes). Combined with other lycophyte plastomes available online, we reconstructed the phylogenetic relationships of the extant lycophytes based on 93 plastomes. We analyzed, traced, and compared the plastomic diversity and divergence of the three lycophyte families (Isoëtaceae, Lycopodiaceae, and Selaginellaceae) in terms of plastomic diversity by comparing their plastome sizes, GC contents, substitution rates, structural rearrangements, divergence times, ancestral states, RNA editings, and gene losses. Comparative analysis of plastid phylogenomics and plastomic diversity of three lycophyte families will set a foundation for further studies in biology and evolution in lycophytes and therefore in vascular plants.
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http://dx.doi.org/10.3390/genes13071280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316050PMC
July 2022

Ectoderm-derived frontal bone mesenchymal stem cells promote traumatic brain injury recovery by alleviating neuroinflammation and glutamate excitotoxicity partially via FGF1.

Stem Cell Res Ther 2022 07 26;13(1):341. Epub 2022 Jul 26.

Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.

Background: Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model.

Methods: A murine TBI model was established by injuring C57BL/6 N mice with moderate-controlled cortical impact to evaluate the extent of brain damage and behavioral deficits. Ectoderm-derived FbMSCs were isolated from the frontal bone and their characteristics were assessed using multiple differentiation assays, flow cytometry and microarray analysis. Brain repairment and functional recovery were analyzed at different days post-injury with or without FbMSC application. Behavioral tests were performed to assess learning and memory improvements. RNA sequencing analysis, immunofluorescence staining, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to examine inflammation reaction and neural regeneration. In vitro co-culture analysis and quantification of glutamate transportation were carried out to explore the possible mechanism of neurogenesis and functional recovery promoted by FbMSCs.

Results: Ectoderm-derived FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs expressed the ectoderm-specific transcription factor Tfap2β. TBI mice showed impaired learning and memory deficits. Microglia and astrocyte activation, as well as neural damage, were significantly increased post-injury. FbMSC application ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. RNA sequencing analysis showed that signal pathways related to inflammation decreased, whereas those related to neural activation increased. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons.

Conclusions: Ectoderm-derived FbMSC application significantly alleviated neuroinflammation, brain injury, and excitatory toxicity to neurons, improved cognition and behavioral deficits in TBI mice. Therefore, ectoderm-derived FbMSCs could be ideal therapeutic candidates for TBI which mostly affect cells from the same embryonic origins as FbMSCs.
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http://dx.doi.org/10.1186/s13287-022-03032-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327213PMC
July 2022

Analysis of functional corticomuscular coupling based on multiscale transfer spectral entropy.

IEEE J Biomed Health Inform 2022 Jul 26;PP. Epub 2022 Jul 26.

Functional corticomuscular coupling (FCMC) between the cerebral motor cortex and muscle activity reflects multi-layer and nonlinear interactions in the sensorimotor system. Considering the inherent multiscale characteristics of physiological signals, we proposed multiscale transfer spectral entropy (MSTSE) and introduced the unidirectionally coupled Hénon maps model to verify the effectiveness of MSTSE. We recorded electroencephalogram (EEG) and surface electromyography (sEMG) in steady-state grip tasks of 29 healthy participants and 27 patients. Then, we used MSTSE to analyze the FCMC base on EEG of the bilateral motor areas and the sEMG of the flexor digitorum superficialis (FDS). The results show that MSTSE is superior to transfer spectral entropy (TSE) method in restraining the spurious coupling and detecting the coupling more accurately. The coupling strength was higher in the β1, β2, and γ 2 bands, among which, it was highest in the β1 band, and reached its maximum at the 22-30 scale. In particular, the coupling strength was higher when the dominant hand or higher grip strengths was used. On the directional characteristics of FCMC, the coupling strength of EEG→sEMG is superior to the opposite direction in most cases. In addition, the coupling strength of the stroke-affected side was lower than that of healthy controls' right hand in the β1 and β2 bands and the stroke-unaffected side in the β1 band. The coupling strength of the stroke-affected side was higher than that of the stroke-unaffected side and the right hand of healthy controls in the sEMG→EEG direction of γ2 band. This study provides a new perspective and lays a foundation for analyzing FCMC and motor dysfunction.
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http://dx.doi.org/10.1109/JBHI.2022.3193984DOI Listing
July 2022
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