Publications by authors named "Jiawei Zhou"

239 Publications

Oxidative stress in oocyte aging and female reproduction.

J Cell Physiol 2021 Jun 14. Epub 2021 Jun 14.

Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan, PR China.

In a healthy body, reactive oxygen species (ROS) and antioxidants remain balanced. When the balance is broken toward an overabundance of ROS, oxidative stress appears and may lead to oocyte aging. Oocyte aging is mainly reflected as the gradual decrease of oocyte quantity and quality. Here, we aim to review the relationship between oxidative stress and oocyte aging. First, we introduced that the defective mitochondria, the age-related ovarian aging, the repeated ovulation, and the high-oxygen environment were the ovarian sources of ROS in vivo and in vitro. And we also introduced other sources of ROS accumulation in ovaries, such as overweight and unhealthy lifestyles. Then, we figured that oxidative stress may act as the "initiator" for oocyte aging and reproductive pathology, which specifically causes follicular abnormally atresia, abnormal meiosis, lower fertilization rate, delayed embryonic development, and reproductive disease, including polycystic ovary syndrome and ovary endometriosis cyst. Finally, we discussed current strategies for delaying oocyte aging. We introduced three autophagy antioxidant pathways like Beclin-VPS34-Atg14, adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), and p62-Keap1-Nrf2. And we also describe the different antioxidants used to combat oocyte aging. In addition, the hypoxic (5% O ) culture environment for oocytes avoiding oxidative stress in vitro. So, this review not only contribute to our general understanding of oxidative stress and oocyte aging but also lay the foundations for the therapies to treat premature ovarian failure and oocyte aging in women.
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http://dx.doi.org/10.1002/jcp.30468DOI Listing
June 2021

Exploration of Crucial Mediators for Carotid Atherosclerosis Pathogenesis Through Integration of Microbiome, Metabolome, and Transcriptome.

Front Physiol 2021 24;12:645212. Epub 2021 May 24.

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Background: Carotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited.

Materials And Methods: We utilized 16S ribosomal DNA sequencing and untargeted metabolomics to investigate the alterations in the gut microbiota and plasma metabolites of 32 CAS patients and 32 healthy controls. The compositions of the gut microbiota differed significantly between the two groups, and a total of 11 differentially enriched genera were identified. In the metabolomic analysis, 11 and 12 significantly changed metabolites were screened in positive (POS) and negative (NEG) modes, respectively. α-N-Phenylacetyl-L-glutamine was an upregulated metabolite in CAS patients detected in both POS and NEG modes and had the highest | log(fold change)| in POS mode. In addition, transcriptomic analysis was performed using the GSE43292 dataset.

Results: A total of 132 differentially expressed genes (DEGs) were screened. Among the upregulated DEGs in CAS patients, FABP4 exhibited the highest | log(fold change)|. Furthermore, FABP4 was positively associated with and had the highest Spearman's correlation coefficient and the most significant -value among the microbiota-DEG pairs.

Conclusion: In this study, we investigated the potential "microbiota-metabolite-gene" regulatory axis that may act on CAS, and our results may help to establish a theoretical basis for further specialized study of this disease.
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http://dx.doi.org/10.3389/fphys.2021.645212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181762PMC
May 2021

Diagnostic Biomarker Hsa_circ_0126218 and Functioning Prediction in Peripheral Blood Monocular Cells of Female Patients With Major Depressive Disorder.

Front Cell Dev Biol 2021 20;9:651803. Epub 2021 May 20.

Psychology and Health Management Center, Harbin Medical University, Harbin, China.

Introduction: Although major depressive diroder (MDD) has brought huge burden and challenges to society globally, effective and accurate diagnoses and treatments remain inadequate. The pathogenesis that for women are more likely to suffer from depression than men needs to be excavated as well. The function of circRNAs in pathological process of depression has not been widely investigated. This study aims to explore potential diagnostic biomarker circRNA of female patients with MDD and to investigate its role in pathogenesis.

Methods: First, an expression profile of circRNAs in the peripheral blood monocular cells of MDD patients and healthy peripherals were established based on high-throughput sequencing analysis. In addition, the top 10 differentially expressed circRNAs were quantified by quantitative real-time PCR to explore diagnostic biomarkers. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes of the biomarkers was carried out.

Results: There is a mass of dysregulated circRNAs in PBMCs between female MDD patients and healthy controls. Among the top 10 differentially expressed circRNAs, hsa_circ_0126218 is more feasible as a diagnostic biomarker. The expression level of hsa_circ_0126218 displayed upregulation in patients with MDD and the area under the operating characteristic curve of hsa_circ_0126218 was 0.801 (95% CI 0.7226-0.8791, < 0.0001). To explain the competing endogenous RNA role of hsa_circ_0126218 in the pathogenesis of female MDD, a hsa_circ_0126218-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of hsa_circ_0126218 are closely related to MDD. Moreover, we established a protein-protein network to further screen out the hub genes (PIK3CA, PTEN, MAPK1, CDC42, Lyn, YES1, EPHB2, SMAD2, STAT1, and ILK). The function of hsa_circ_0126218 was refined by constructing a verified circRNA-predicted miRNA-hub gene subnetwork.

Conclusion: hsa_circ_0126218 can be considered as a new female MDD biomarker, and the pathogenesis of female MDD by the downstream regulation of hsa_circ_0126218 has been predicted. These findings may help further improve the early detection, effective diagnosis, convenient monitoring of complications, precise treatment, and timely recurrence prevention of depression.
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http://dx.doi.org/10.3389/fcell.2021.651803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174117PMC
May 2021

Influence of Sedation on the Detection Rate of Early Cancer and Precancerous Lesions During Diagnostic Upper Gastrointestinal Endoscopies: A Multicenter Retrospective Study.

Am J Gastroenterol 2021 Jun;116(6):1230-1237

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Introduction: The influence of sedation on the endoscopic detection rate of upper gastrointestinal (UGI) early cancer (EC) and precancerous lesions, including high-grade intraepithelial neoplasia (HGIN) and low-grade intraepithelial neoplasia, has not been assessed. The aim of this research is to assess whether the use of sedation can help improve the detection rate of UGI EC and precancerous lesions. The second objective is to evaluate its potential influencing factors.

Methods: The study includes 432,202 patients from a multicenter database from January 2012 to July 2019. Information on endoscopic findings and histology biopsies was obtained from endoscopy quality-control system. Associations of sedation with the detection rate of EC and precancerous lesions were assessed.

Results: The sedation group has a higher detection rate of UGI EC and HGIN compared with the no-sedation group, whereas the detection rate of low-grade intraepithelial neoplasia was similar between the 2 groups. There were more cases examined by using staining, image enhancement, or magnifying techniques in the sedation group (P < 0.001). And, the mean observation time was also longer in the sedation group (P < 0.001). The type 0-IIb esophageal HGIN and EC cases were significantly increased in the sedation group. No significant difference was detected on lesion subtypes for gastric HGIN and EC according to the Paris classification. More gastric HGIN and EC were detected at gastric body in the sedation group (P = 0.001).

Discussion: Sedation may improve the endoscopic detection rate of EC and HGIN in the UGI tract probably through enhancing the use of accessary endoscopic techniques, prolonging observation time, and taking more biopsies in different locations (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B926).
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http://dx.doi.org/10.14309/ajg.0000000000001201DOI Listing
June 2021

M2 subtype tumor associated macrophages (M2-TAMs) infiltration predicts poor response rate of immune checkpoint inhibitors treatment for prostate cancer.

Ann Med 2021 Dec;53(1):730-740

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Background: Prostate cancer (PCa) is poor response to the immunotherapy for its high heterogeneity of immune microenvironment. In this study, we aim to introduce a new immune subtype for PCa involving M2 tumour associated macrophages M2-TAMs).

Methods: Three hundred and sixty-two PCa patients and matched normal prostate tissues were selected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Patients' immune infiltration characters were then analyzed based on the gene expressions. The immune subtypes were identified by the method of unsupervised hierarchical clustering. Finally, the relationship between the M2-TAMs infiltration and anti-programmed death-ligand-1 (PD-L1) therapy was investigated in the IMvigor210 cohort.

Results: PCa expressed lower immune-related genes levels compared with the adjacent normal tissues. Based on the proved immunosuppressive mechanisms in PCa, tumour patients were classified into three independent subclasses with high infiltrated cytolytic activity (CYT), M2-TAMs and regulatory T cell (Tregs), respectively. Among these subtypes, M2-TAMs infiltration subtype showed the worst clinicopathological features and prognosis compared with the other two subtypes. The results of the IMvigor210 cohort demonstrated poor response of anti-PD-L1 therapy for patients with high M2-TAMs infiltration.

Conclusion: Prostate tumours involved in significant immunosuppression, and high infiltration of M2-TAMs can be applied to predict the effect of anti-PD-L1 therapy.Key MessagesPCa patients can be classified into three immunotypes of high infiltrated CYT, M2-TAMS, and Tregs according to the immunosuppressive mechanisms.High M2-TAMs infiltration subtype reflected the worst clinical characters, immune infiltration, and lowest expression of immune checkpoint inhibitors among the three subclasses in PCa.High M2-TAMs infiltration predicts the low response rate of anti-PD-L1 therapy.
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http://dx.doi.org/10.1080/07853890.2021.1924396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158194PMC
December 2021

Changes in Biothiol Levels Are Closely Associated with Alzheimer's Disease.

J Alzheimers Dis 2021 May 19. Epub 2021 May 19.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China.

Background: Serum homocysteine (Hcy) level is considered to be an important biomarker for Alzheimer's disease (AD); however, the status of Hcy in brain tissue, and the association between brain and serum levels of Hcy in AD patients remain unclear.

Objective: We aimed to examine whether the changes of three thiols are consistent in serum of AD patients and the brain of APP/PS1 mice, and to verify the effectiveness of Hcy as a biomarker for early AD detection.

Methods: The levels of Hcy, cysteine (Cys), and glutathione (GSH) in Aβ 1-42-treated PC12 cells, the brain and hippocampus of APP/PS1 mouse, and the serum of AD patients were evaluated using ethyl (E)-3-(9-chloro-11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f] pyrido [3,2,1 -ij] quinolin-10-yl)-2-cyanoacrylate (Probe 1) and ELISA assay or LC-MS.

Results: Measurement by Probe 1 revealed a significant increase in Hcy level, and a decrease in Cys and GSH levels in Aβ1-42-treated PC12 cells and the serum of AD patients. The hippocampus and whole brain of APP/PS1 mice also showed a significant increase in Hcy level alongside the accumulation of age-related AD symptoms. The upregulation of Hcy and the downregulation of Cys and GSH were reversed in the Aβ1-42-treated PC12 cells and the brain of APP/PS1 mice when supplemented with VB6.

Conclusion: Changes in Hcy, Cys, and GSH levels in the brain of APP/PS1 mice and Aβ 1-42-treated PC12 cells were observed in situ with a new fluorescent probe, which were consistent with the abnormal changes in Hcy, Cys, and GSH levels in the serum of AD patients. VB6 supplementation was successful in ameliorating abnormal increases in Hcy levels.
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http://dx.doi.org/10.3233/JAD-210021DOI Listing
May 2021

Roles of Anxiety and Depression in Predicting Cardiovascular Disease Among Patients With Type 2 Diabetes Mellitus: A Machine Learning Approach.

Front Psychol 2021 28;12:645418. Epub 2021 Apr 28.

Department of Medical Psychology, Harbin Medical University, Harbin, China.

Cardiovascular disease (CVD) is a major complication of type 2 diabetes mellitus (T2DM). In addition to traditional risk factors, psychological determinants play an important role in CVD risk. This study applied Deep Neural Network (DNN) to develop a CVD risk prediction model and explored the bio-psycho-social contributors to the CVD risk among patients with T2DM. From 2017 to 2020, 834 patients with T2DM were recruited from the Department of Endocrinology, Affiliated Hospital of Harbin Medical University, China. In this cross-sectional study, the patients' bio-psycho-social information was collected through clinical examinations and questionnaires. The dataset was randomly split into a 75% train set and a 25% test set. DNN was implemented at the best performance on the train set and applied on the test set. The receiver operating characteristic curve (ROC) analysis was used to evaluate the model performance. Of participants, 272 (32.6%) were diagnosed with CVD. The developed ensemble model for CVD risk achieved an area under curve score of 0.91, accuracy of 87.50%, sensitivity of 88.06%, and specificity of 87.23%. Among patients with T2DM, the top five predictors in the CVD risk model were body mass index, anxiety, depression, total cholesterol, and systolic blood pressure. In summary, machine learning models can provide an automated identification mechanism for patients at CVD risk. Integrated treatment measures should be taken in health management, including clinical care, mental health improvement, and health behavior promotion.
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http://dx.doi.org/10.3389/fpsyg.2021.645418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113686PMC
April 2021

Evaluation of fetal foramen ovale blood flow by pulsed Doppler ultrasonography combined with spatiotemporal image correlation : To define the normal reference range of fetal foramen ovale blood volume for each gestational age: a cross-sectional study.

Cardiovasc Ultrasound 2021 May 5;19(1):18. Epub 2021 May 5.

Department of Ultrasound Diagnosis, The Third People Hospital of Yongzhou, Yongzhou, China.

Objective: The objective of this study was to determine fetal foramen ovale blood flow utilizing pulsed Doppler combined with spatiotemporal image correlation.

Methods: A cross-sectional study was performed in 440 normal fetuses between 20 and 40 weeks of gestation. In order to calculate foramen ovale blood flow, the foramen ovale flow velocity-time integral was obtained by pulsed Doppler ultrasonography, and the foramen ovale area was measured by using spatiotemporal image correlation rendering mode. Foramen ovale blood flow was calculated as the product of the foramen ovale area and the velocity-time integral.

Results: Gestational age-specific reference ranges are given for the absolute blood flow (ml/min) of foramen ovale, showing an exponential increase from 20 to 30 weeks of gestation, and a flat growth trend during the last trimester, while the weight-indexed flow (ml/min/kg) of foramen ovale decreased significantly. The median weight-indexed foramen ovale blood flow was 320.82 ml/min/kg (mean 319.1 ml/min/kg; SD 106.33 ml/min/kg).

Conclusions: The reference range for fetal foramen ovale blood flow was determined from 20 to 40 weeks of gestation. The present data show that the volume of foramen ovale blood flow might have a limited capacity to increase during the last trimester.
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http://dx.doi.org/10.1186/s12947-021-00247-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101195PMC
May 2021

Chloroplast genomes in Populus (Salicaceae): comparisons from an intensively sampled genus reveal dynamic patterns of evolution.

Sci Rep 2021 May 4;11(1):9471. Epub 2021 May 4.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

The chloroplast is one of two organelles containing a separate genome that codes for essential and distinct cellular functions such as photosynthesis. Given the importance of chloroplasts in plant metabolism, the genomic architecture and gene content have been strongly conserved through long periods of time and as such are useful molecular tools for evolutionary inferences. At present, complete chloroplast genomes from over 4000 species have been deposited into publicly accessible databases. Despite the large number of complete chloroplast genomes, comprehensive analyses regarding genome architecture and gene content have not been conducted for many lineages with complete species sampling. In this study, we employed the genus Populus to assess how more comprehensively sampled chloroplast genome analyses can be used in understanding chloroplast evolution in a broadly studied lineage of angiosperms. We conducted comparative analyses across Populus in order to elucidate variation in key genome features such as genome size, gene number, gene content, repeat type and number, SSR (Simple Sequence Repeat) abundance, and boundary positioning between the four main units of the genome. We found that some genome annotations were variable across the genus owing in part from errors in assembly or data checking and from this provided corrected annotations. We also employed complete chloroplast genomes for phylogenetic analyses including the dating of divergence times throughout the genus. Lastly, we utilized re-sequencing data to describe the variations of pan-chloroplast genomes at the population level for P. euphratica. The analyses used in this paper provide a blueprint for the types of analyses that can be conducted with publicly available chloroplast genomes as well as methods for building upon existing datasets to improve evolutionary inference.
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http://dx.doi.org/10.1038/s41598-021-88160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096831PMC
May 2021

Two Small Extracellular Vesicle sRNAs Derived From Serve as Diagnostic Biomarkers for Active Pulmonary Tuberculosis.

Front Microbiol 2021 15;12:642559. Epub 2021 Apr 15.

Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified encoded-sRNAs in the serum/plasm of infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles encoded sRNA (sRNA) by qRT-PCR. The results showed that encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis.
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http://dx.doi.org/10.3389/fmicb.2021.642559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082067PMC
April 2021

The Relationship between Achievement Motivation and Job Performance among Chinese Physicians: A Conditional Process Analysis.

Biomed Res Int 2021 7;2021:6646980. Epub 2021 Apr 7.

Department of Medical Education, School of Health Management, Harbin Medical University, Heilongjiang Province, China.

Background: To explore the relationship between achievement motivation and job performance among physicians, this study investigated the impacts of different personality traits on job performance among the physicians.

Methods: This cross-sectional study was conducted in 2017 and 1,523 physicians from eight tertiary grade A hospitals in Harbin, China. The type of data collected included the achievement motivation of the physicians, job performance, organizational commitment, personality traits, and other demographic variables. To assess and compare the demographic data, independent -test and ANOVA were applied. Further, Pearson correlation coefficients were used to evaluate the correlation among the variables. Moderated mediation analysis was performed to test the correlation among the job performance, achievement motivation, organizational commitment, neuroticism, extraversion, openness, agreeableness, and conscientiousness.

Results: Achievement motivation directly influences job performance and organizational commitment partially mediates the direct effects of achievement motivation on job performance. Additionally, our findings demonstrated that agreeableness and conscientiousness moderate the strength of the relationships between achievement motivation and job performance mediated by organizational commitment.

Conclusion: We propose that hospital managers should pay attention to the personal growth of the physicians and improve their organizational commitment via creating a positive working climate and training for career planning and education. Moreover, managers should identify conscientiousness and agreeableness individuals and increase their responsibilities geared towards improving the performance of the organization.
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http://dx.doi.org/10.1155/2021/6646980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049801PMC
May 2021

A Randomized Clinical Trial Comparing Eyetronix Flicker Glass and Patching for Treatment of Amblyopia in Children Reveals Similar Improvements in Vision.

Front Neurosci 2021 9;15:622729. Epub 2021 Apr 9.

School of Ophthalmology and Optometry and Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, China.

Purpose: Recently, Eyetronix Flicker Glass (EFG) has been introduced as a novel treatment for amblyopia. It alternatively deprives the visual input of each eye rapidly (e.g., 7 Hz). However, whether it is comparable with standard patching therapy is unclear. In this randomized clinical trial, we evaluate the efficacy of an EFG therapy as treatment for amblyopia in children and compare it to the patching therapy.

Methods: We tested 31 children (aged 4-13 years) with amblyopia. They were assigned into one of the two treatment groups and were treated for 12 weeks. The first group was treated with EFG for 1 h/day (Flicker Group) and the latter with a standard patch (Patching Group) for 2 h/day. We designated changes from baseline in best-corrected visual acuity (BCVA) of the amblyopic eye as our primary outcome. Changes from baseline in other visual outcomes, such as contrast sensitivity, stereopsis, and fusional vergence range were measured as secondary outcome.

Results: BCVA improved significantly at 12 weeks relative to baseline in both the Flicker (0.13 ± 0.11 logMAR; mean ± SD) and Patching Groups (0.21 ± 0.14 logMAR). However, the improvements were not significantly different between groups ( = 0.13). Contrast sensitivity also significantly improved at 3 and 12 cycles/degree between baseline and 12 weeks in both groups ('s < 0.05). However, stereopsis and fusion range did not improve significantly in both groups.

Conclusion: An EFG therapy and patching improved BCVA similarly for children with amblyopia at 12 weeks. Both therapies improved the contrast sensitivity at 3 and 12 cycles per degree (cpd); however, only patching improved the contrast sensitivity at 6 cpd. Both therapies did not benefit binocular visual functions (stereopsis and fusional vergence range). We believe that EFG can be an additional choice for therapy.

Clinical Trial Registration: chictr.org number: ChiCTR2000034436.
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http://dx.doi.org/10.3389/fnins.2021.622729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063027PMC
April 2021

Proteomic and lipidomic analyses reveal saturated fatty acids, phosphatidylinositol, phosphatidylserine, and associated proteins contributing to intramuscular fat deposition.

J Proteomics 2021 06 22;241:104235. Epub 2021 Apr 22.

Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, China; Hubei Key Lab for Animal Embryo Engineering and Molecular Breeding, Wuhan 430064, China. Electronic address:

Intramuscular fat (IMF) content is an important factor in porcine meat quality. Previous studies have screened multiple candidate genes related to IMF deposition, but the lipids that affect IMF deposition and their lipid-protein network remain unknown. In this study, we performed proteomic and lipidomic analyses of the longissimus dorsi (LD) muscle from high-IMF (IMFH) and low-IMF (IMF-L) groups of Xidu black pigs. Eighty-eight proteins and 143 lipids were differentially abundant between the groups. The differentially abundant proteins were found to be involved in cholesterol metabolism, the PPAR signaling pathway, and ferroptosis. The triacylglycerols (TAGs) upregulated in the IMF-H group were mainly shown to be synthesized by saturated fatty acids (SFAs), while the downregulated TAGs were mainly synthesized by polyunsaturated fatty acids (PUFAs). All differentially abundant phosphatidylinositols (PIs) and phosphatidylserines (PSs) were found to be upregulated in the IMF-H group. A correlation analysis of the proteomic and lipidomic revealed candidate proteins (APOA4, VDAC3, PRNP, CTSB, GSPT1) related to TAG, PI, and PS lipids. These results revealed differences in proteins and lipids between the IMF-H and IMF-L groups, which represent new candidate proteins and lipids that should be investigated to determine the molecular mechanisms controlling IMF deposition in pigs. SIGNIFICANCE: Intramuscular fat (IMF) is a key factor affecting meat quality, and meat with a higher IMF content can have a better flavor. In this study, proteomic results show that the ferroptosis pathway, including the PRNP, VDAC3 and CP proteins, affects IMF deposition. Lipid composition is the key factor affecting IMF deposition, but there are few reports on this. In this study, through lipidomic analysis, we suggest that saturated fatty acid (SFA), phosphatidylinositol (PI), and phosphatidylserine (PS) may contribute to IMF deposition. A correlation analysis reveals the potential regulatory network between lipids and proteins. This study clarifies the difference in protein and lipid compositions in longissimus dorsi (LD) muscle with high and low IMF contents. This information suggests that it would be beneficial to increase the intramuscular fat content of pork not only from a genetic perspective but also from a nutritional perspective.
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http://dx.doi.org/10.1016/j.jprot.2021.104235DOI Listing
June 2021

lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR axis in cerebral ischemia-reperfusion injury.

Aging (Albany NY) 2021 04 4;13(8):11315-11335. Epub 2021 Apr 4.

Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal University, Nanyang 473000, China.

Cerebral ischemia-reperfusion injury (CIRI) is an important pathophysiological process of ischemic stroke associated with various physiological and pathological processes, including autophagy and apoptosis. In this study, we examined the role and mechanism of long noncoding RNA CAMK2D-associated transcript 2 (C2dat2) in regulating CIRI and . C2dat2 up-regulation facilitated neuronal autophagy and apoptosis induced by CIRI. Mechanistically, C2dat2 acts as a competing endogenous RNA (ceRNA) to negatively regulate miR-30d-5p expression. More specifically, miR-30d-5p targeted the 3'-untranslated region of DNA damage-inducible transcript 4 (DDIT4) and silenced its target mRNA DDIT4. Additionally, C2dat2 binding with heat shock cognate 70/heat shock protein 90 blocked RNA-induced silencing complex assembly to abolish the miR-30d-5p targeting of DDIT4 and inhibited miR-30d-5p to silence its target mRNA DDIT4. Further analysis showed that C2dat2 knockdown conspicuously inhibited the up-regulation of DDIT4 and Beclin-1 levels and LC3B II/I ratio and the down-regulation of P62 and phosphorylated mammalian target of rapamycin (mTOR)/mTOR and phosphorylated-P70S6K/P70S6K ratio in Neuro-2a cells after oxygen-glucose deprivation/reoxygenation. This study first revealed that C2dat2/miR-30d-5p/DDIT4/mTOR forms a novel signaling pathway to facilitate autophagy and apoptosis induced by CIRI, contributing to the better understanding of the mechanisms of CIRI and enriching the ceRNA hypothesis in CIRI.
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http://dx.doi.org/10.18632/aging.202824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109078PMC
April 2021

Self-Perpetuating Carbon Foam Microwave Plasma Conversion of Hydrocarbon Wastes into Useful Fuels and Chemicals.

Environ Sci Technol 2021 05 6;55(9):6239-6247. Epub 2021 Apr 6.

Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

White wastes (unseparated plastics, face masks, textiles, etc.) pose a serious challenge to sustainable human development and the ecosystem and have recently been exacerbated due to the surge in plastic usage and medical wastes from COVID-19. Current recycling methods such as chemical recycling, mechanical recycling, and incineration require either pre-sorting and washing or releasing CO. In this work, a carbon foam microwave plasma process is developed, utilizing plasma discharge to generate surface temperatures exceeding ∼3000 K in a N atmosphere, to convert unsorted white wastes into gases (H, CO, CH, CH, CH, etc.) and small amounts of inorganic minerals and solid carbon, which can be buried as artificial "coal". This process is self-perpetuating, as the new solid carbon asperities grafted onto the foam's surface actually increase the plasma discharge efficiency over time. This process has been characterized by optical probes and infrared sensors and optimized to handle most of the forms of white waste without the need for pre-sorting or washing. Thermal measurement and modeling show that in a flowing reactor, the device can achieve locally extremely high temperatures, but the container wall will still be cold and can be made with cheap materials, and thus, a miniaturized waste incinerator is possible that also takes advantage of intermittent renewable electricity.
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http://dx.doi.org/10.1021/acs.est.0c06977DOI Listing
May 2021

The Impact of Transformational Leadership on Physicians' Performance in China: A Cross-Level Mediation Model.

Front Psychol 2021 9;12:586475. Epub 2021 Mar 9.

Harbin Medical University, Harbin, China.

Transformational leadership has been becoming increasingly vital to the provision of high-quality health care, particularly during major public health emergencies. The present study aims to investigate the impact of transformational leadership on physicians' performance and explore the cross-level underlying mechanisms with achievement motivations and coping styles among Chinese physicians. During 2017-2019, 1,527 physicians of 101 departments were recruited from six hospitals in China with a cluster random sampling method. Participants completed several questionnaires regarding their job performance, achievement motivations, coping styles, and transformational leadership. Multilevel mediation effects were tested using cross-level path analysis. The result of this study indicated that transformational leadership was applied well in Chinese medical settings with a score of 101.56 ± 6.42. The hierarchical linear model showed that transformational leadership had a cross-level direct positive effect on physicians' performance (β = 1.524, < 0.05). Furthermore, results of cross-level path analyses revealed that transformational leadership contributed to physicians' performance by sequentially influencing achievement motivations first and then coping styles. In addition, the path "transformational leadership → positive coping (PC) style → physicians' performance" showed the strongest cross-level indirect effect. In summary, public health leaders should enhance physicians' performance by promoting individual development, especially achievement motivation and PC style.
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http://dx.doi.org/10.3389/fpsyg.2021.586475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006430PMC
March 2021

M-CSF, IL-6, and TGF-β promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery.

Sci Adv 2021 Mar 12;7(11). Epub 2021 Mar 12.

Neurosurgical Institute, Fudan University, Shanghai 200040 China.

Traumatic brain injury (TBI) leads to high mortality rate. We aimed to identify the key cytokines favoring TBI repair and found that patients with TBI with a better outcome robustly increased concentrations of macrophage colony-stimulating factor, interleukin-6, and transforming growth factor-β (termed M6T) in cerebrospinal fluid or plasma. Using TBI mice, we identified that M2-like macrophage, microglia, and endothelial cell were major sources to produce M6T. Together with the in vivo tracking of mCherry+ macrophages in zebrafish models, we confirmed that M6T treatment accelerated blood-borne macrophage infiltration and polarization toward a subset of tissue repair macrophages that expressed similar genes as microglia for neuroprotection, angiogenesis and cell migration. M6T therapy in TBI mice and zebrafish improved neurological function while blocking M6T-exacerbated brain injury. Considering low concentrations of M6T in some patients with poor prognostic, M6T treatment might repair TBI via generating a previously unidentified subset of tissue repair macrophages.
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http://dx.doi.org/10.1126/sciadv.abb6260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954455PMC
March 2021

AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis.

J Exp Med 2021 May;218(5)

Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Center for Global Health, Nanjing Medical University, Nanjing, China.

The role of the PYHIN family member absent in melanoma 2 (AIM2), another important inflammasome sensor, in EAE remains unclear. In this study, we found that AIM2 negatively regulates the pathogenesis of EAE independent of inflammasome activation. AIM2 deficiency enhanced microglia activation and infiltration of peripheral immune cells into the CNS, thereby promoting neuroinflammation and demyelination during EAE. Mechanistically, AIM2 negatively regulates the DNA-PK-AKT3 in microglia to control neuroinflammation synergistically induced by cGAS and DNA-PK. Administration of a DNA-PK inhibitor reduced the severity of the EAE. Collectively, these findings identify a new role for AIM2 in controlling the onset of EAE. Furthermore, delineation of the underlying inflammasome-independent mechanism highlights cGAS and DNA-PK signaling as potential targets for the treatment of heterogeneous MS.
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http://dx.doi.org/10.1084/jem.20201796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961553PMC
May 2021

Phonon-engineered extreme thermal conductivity materials.

Nat Mater 2021 Mar 8. Epub 2021 Mar 8.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Materials with ultrahigh or low thermal conductivity are desirable for many technological applications, such as thermal management of electronic and photonic devices, heat exchangers, energy converters and thermal insulation. Recent advances in simulation tools (first principles, the atomistic Green's function and molecular dynamics) and experimental techniques (pump-probe techniques and microfabricated platforms) have led to new insights on phonon transport and scattering in materials and the discovery of new thermal materials, and are enabling the engineering of phonons towards desired thermal properties. We review recent discoveries of both inorganic and organic materials with ultrahigh and low thermal conductivity, highlighting heat-conduction physics, strategies used to change thermal conductivity, and future directions to achieve extreme thermal conductivities in solid-state materials.
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http://dx.doi.org/10.1038/s41563-021-00918-3DOI Listing
March 2021

Phonon-engineered extreme thermal conductivity materials.

Nat Mater 2021 Mar 8. Epub 2021 Mar 8.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Materials with ultrahigh or low thermal conductivity are desirable for many technological applications, such as thermal management of electronic and photonic devices, heat exchangers, energy converters and thermal insulation. Recent advances in simulation tools (first principles, the atomistic Green's function and molecular dynamics) and experimental techniques (pump-probe techniques and microfabricated platforms) have led to new insights on phonon transport and scattering in materials and the discovery of new thermal materials, and are enabling the engineering of phonons towards desired thermal properties. We review recent discoveries of both inorganic and organic materials with ultrahigh and low thermal conductivity, highlighting heat-conduction physics, strategies used to change thermal conductivity, and future directions to achieve extreme thermal conductivities in solid-state materials.
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http://dx.doi.org/10.1038/s41563-021-00918-3DOI Listing
March 2021

The Effects of 0.01% Atropine on Adult Myopes' Contrast Sensitivity.

Front Neurosci 2021 19;15:624472. Epub 2021 Feb 19.

State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Purpose: Atropine at a low concentration is considered a safe and effective treatment to mitigate myopia progression. However, the potential unwanted side effects of administering atropine at a low dose on visual functions other than best corrected visual acuity has not been investigated. In this study, we investigate the short-term (12,16, and 20 h) and long-term (1, 2, and 4 weeks) effects of 0.01% atropine (i.e., 0.1 mg/ml) on contrast sensitivity (CS) in patients with myopia.

Methods: Thirty adults (23.33 ± 2.93 years old) with myopia between -1.00 and -6.00 diopters (D), astigmatism of -1.50 D or less, and anisometropia of 1.00 D or less, participated in this prospective, masked, placebo-controlled, randomized study. The participants were randomly assigned to receive 0.01% atropine or polyvinyl alcohol eye drops once nightly to both eyes for four weeks. CS was measured binocularly at baseline and 12, 16, 20 h, 1, 2, and 4 weeks after the first use of the eye drops.

Results: There was no statistically significant differences of CS found between atropine and placebo-controlled groups in both short-term and long-term. There was no statistically significant interaction effect found between the time and group.

Conclusion: We demonstrated no significant deleterious effect of 0.01% atropine on adult myopes' CS.
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http://dx.doi.org/10.3389/fnins.2021.624472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933202PMC
February 2021

Interactions Between Glycogen Synthase Kinase-3β Gene Polymorphisms, Negative Life Events, and Susceptibility to Major Depressive Disorder in a Chinese Population.

Front Psychiatry 2020 15;11:503477. Epub 2021 Feb 15.

Department of Health Management, Public Health Institute, Harbin Medical University, Harbin, China.

Recent studies suggest that glycogen synthase kinase (GSK)-3β is involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the interaction between GSK-3β polymorphism (rs6438552, rs334558, and rs2199503) and negative life events in the pathogenesis of major depressive disorder (MDD). DNA genotyping was performed on peripheral blood leukocytes in 550 patients with MDD and 552 age- and gender-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A chi-square method was employed to assess the gene-environment interaction (G × E). Differences in rs6438552, rs334558, and rs2199503 genotype distributions were observed between MDD patients and controls. Significant G × E interactions between allelic variation of rs6438552, rs334558, and rs2199503 and negative life events were observed. Individuals with negative life events and carrying genotypes of rs6438552 A, rs334558 A, and rs2199503G have increased the risk of depression. These results indicate that interactions between the GSK-3β rs6438552, rs334558, and rs2199503 polymorphisms and environment increases the risk of developing MDD.
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http://dx.doi.org/10.3389/fpsyt.2020.503477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917206PMC
February 2021

Weighted Gene Co-expression Network Analysis Identifies Crucial Genes Mediating Progression of Carotid Plaque.

Front Physiol 2021 5;12:601952. Epub 2021 Feb 5.

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Surface rupture of carotid plaque can cause severe cerebrovascular disease, including transient ischemic attack and stroke. The aim of this study was to elucidate the molecular mechanism governing carotid plaque progression and to provide candidate treatment targets for carotid atherosclerosis.

Methods: The microarray dataset GSE28829 and the RNA-seq dataset GSE104140, which contain advanced plaque and early plaque samples, were utilized in our analysis. Differentially expressed genes (DEGs) were screened using the "limma" R package. Gene modules for both early and advanced plaques were identified based on co-expression networks constructed by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses were employed in each module. In addition, hub genes for each module were identified. Crucial genes were identified by molecular complex detection (MCODE) based on the DEG co-expression network and were validated by the GSE43292 dataset. Gene set enrichment analysis (GSEA) for crucial genes was performed. Sensitivity analysis was performed to evaluate the robustness of the networks that we constructed.

Results: A total of 436 DEGs were screened, of which 335 were up-regulated and 81 were down-regulated. The pathways related to inflammation and immune response were determined to be concentrated in the black module of the advanced plaques. The hub gene of the black module was (Rho GTPase activating protein 18). (neutrophil cytosolic factor 2), (IQ motif containing GTPase activating protein 2) and (CD86 molecule) had the highest connectivity among the crucial genes. All crucial genes were validated successfully, and sensitivity analysis demonstrated that our results were reliable.

Conclusion: To the best of our knowledge, this study is the first to combine DEGs and WGCNA to establish a DEG co-expression network in carotid plaques, and it proposes potential therapeutic targets for carotid atherosclerosis.
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http://dx.doi.org/10.3389/fphys.2021.601952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894049PMC
February 2021

Spatiotemporal Heterogeneity across Metastases and Organ-Specific Response Informs Drug Efficacy and Patient Survival in Colorectal Cancer.

Cancer Res 2021 May 15;81(9):2522-2533. Epub 2021 Feb 15.

Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina.

The sum of target lesions is routinely used to evaluate patient objective responses to treatment in the RECIST criteria, but it fails to address response heterogeneity across metastases. This study argues that spatiotemporal heterogeneity across metastases and organ-specific response is informative for drug efficacy and patient survival. We analyzed the longitudinal data of 11,404 metastatic lesions in 2,802 colorectal cancer patients from five phase III clinical trials. Initially, a metric Gower distance was applied to quantify response heterogeneity across metastases. Next, the spatiotemporal response heterogeneity across anatomic sites, therapies, and mutation status was assessed and examined for its association with drug efficacy and long-term patient survival. The response of metastatic lesions broadly differed across anatomic sites and therapies. About 60% of patients had at least one lesion respond contrarily from total tumor size. High interlesion heterogeneity was associated with shorter progression-free survival and overall survival. Targeted therapies (bevacizumab or panitumumab) combined with standard chemotherapy reduced interlesion heterogeneity and elicited more favorable effects from liver lesions ( < 0.001) than chemotherapy alone. Moreover, the favorable responses in liver metastases (> 30% shrinkage) were associated with extended patient overall survival ( < 0.001), in contrast to lesions in the lungs and lymph nodes. Altogether, the spatiotemporal response heterogeneity across metastases informed drug efficacy and patient survival, which could improve the current methods for treatment evaluation and patient prognosis. SIGNIFICANCE: These findings support the modification of RECIST criteria to include individual lesion response to improve assessments of drug efficacy.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137573PMC
May 2021

The chromosome-level reference genome assembly for and insights into ginsenoside biosynthesis.

Plant Commun 2021 Jan 20;2(1):100113. Epub 2020 Sep 20.

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

, a perennial herb of the genus in the family Araliaceae, has played an important role in clinical treatment in China for thousands of years because of its extensive pharmacological effects. Here, we report a high-quality reference genome of , with a genome size up to 2.66 Gb and a contig N50 of 1.12 Mb, produced with third-generation PacBio sequencing technology. This is the first chromosome-level genome assembly for the genus . Through genome evolution analysis, we explored phylogenetic and whole-genome duplication events and examined their impact on saponin biosynthesis. We performed a detailed transcriptional analysis of and explored gene-level mechanisms that regulate the formation of characteristic tubercles. Next, we studied the biosynthesis and regulation of saponins at temporal and spatial levels. We combined multi-omics data to identify genes that encode key enzymes in the terpenoid biosynthetic pathway. Finally, we identified five glycosyltransferase genes whose products catalyzed the formation of different ginsenosides in . The genetic information obtained in this study provides a resource for further exploration of the growth characteristics, cultivation, breeding, and saponin biosynthesis of .
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http://dx.doi.org/10.1016/j.xplc.2020.100113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816079PMC
January 2021

Identification of therapeutic targets and prognostic biomarkers from the hnRNP family in invasive breast carcinoma.

Aging (Albany NY) 2021 01 20;13(3):4503-4521. Epub 2021 Jan 20.

Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal University, NanYang 473000, China.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins that are reported to play a crucial role in the pathogenic process of multiple malignancies. However, their expression patterns, clinical application significance and prognostic values in invasive breast carcinoma (BRCA) remain unknown. In this study, we investigated hnRNP family members in BRCA using accumulated data from Oncomine 4.5, UALCAN Web portal and other available databases. We explored the expression and prognostic value level of hnRNPs in BRCA. We further analyzed their association with the clinicopathological features of BRCA patients. Subsequently, we calculated the alteration frequency of hnRNPs, constructed the interaction network of hnRNPs, and examined the potential coexpression genes of hnRNPs, revealing that HNRNPU and SYNCRIP are the core molecular genes requiring further investigation for BRCA. We validated the immunohistochemistry (IHC) pattern to simulate clinical applications based on pathology. Cell function experiments conducted indicated that HNRNPU can promote epithelial-mesenchymal transition, functionally stimulating the invasion capacity and inhibiting the viability of invasive BRCA cells. In summary, our systematic analysis demonstrated that HNRNPU was the key molecule that played a fundamental role in BRCA metastasis, which may facilitate the development of new diagnostic and prognostic markers for the analysis of BRCA progression.
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http://dx.doi.org/10.18632/aging.202411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906176PMC
January 2021

Identify the Early Predictor of Mortality in Patients with Acute Paraquat Poisoning.

Biomed Res Int 2020 31;2020:8894180. Epub 2020 Dec 31.

Department of Emergency, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.

Background: Paraquat is a widely used nonselective and fast-acting contact herbicide worldwide. This study identified the early predictor of mortality in patients with acute paraquat poisoning.

Methods: Twenty-nine patients with acute paraquat poisoning admitted at Nanjing Drum Tower Hospital from January 2018 to August 2020 were included in this study. The early predictor of mortality in patients with acute paraquat poisoning based on the blood tests was identified by correlation, logistic regression, and receiver operating characteristic (ROC) analyses.

Result: 15 of the 29 patients died after poisoning. Compared to the survivors, the neutrophilic granulocyte ratio, leukocyte count, ALB, and Crea of the nonsurvivors were significantly higher with value < 0.05, while the lymphocyte ratio and eGFR(MDRD) of the nonsurvivors were remarkably lower with value < 0.01. Moreover, the neutrophil-to-lymphocyte ratio (NLR) was remarkably upregulated in the nonsurvivors. The area under the ROC curve (AUC) of the neutrophilic granulocyte ratio, lymphocyte ratio, leukocyte count, ALB, Crea, eGFR(MDRD), and NLR to predict the mortality in patients with acute paraquat poisoning was 0.8905 (95% CI: 0.7589-1.022), 0.8643 (95% CI: 0.7244-1.004), 0.8500 (95% CI: 0.7133-0.9867), 0.7286 (95% CI: 0.5338-0.9233), 0.8167 (95% CI: 0.6620-0.9713), 0.8714 (95% CI: 0.7330-1.010), and 0.8667 (95% CI: 0.7277-1.006), respectively. More interestingly, we also evaluated the diagnostic values of the different combinations of six blood test biomarkers by logistic regression analysis. According to the results of the logistic regression analysis, the AUCs for the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) were the largest with 0.986 (95% CI: 0.952-1), and the sensitivity and specificity were 100% and 100%.

Conclusion: This study demonstrated that the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) could serve as an ideal early predictor of mortality in patients with acute paraquat poisoning. However, further research is needed to draw a clear conclusion.
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http://dx.doi.org/10.1155/2020/8894180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790583PMC
May 2021

Long-term kappa-carrageenan consumption leads to moderate metabolic disorder by blocking insulin binding.

Pharmacol Res 2021 Mar 2;165:105417. Epub 2021 Jan 2.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang, 315211, China. Electronic address:

Carrageenan (CGN) is a common food additive, and questions have been raised regarding its safety for human consumption. The purpose of this study was to investigate the impact of κ-CGN on glucose intolerance and insulin resistance from the perspective that κ-CGN may interfere with insulin receptor function and affect insulin sensitivity and signaling, thereby leading to body weight loss. The health effects of κ-CGN on C57BL/6 mice were assessed over a 90-d period by monitoring changes in body weight, glucose tolerance, insulin tolerance, fasting glucose and insulin levels, and expression of insulin-pathway-related proteins. Furthermore, HepG2 cells were used to detect the binding of κ-CGN on insulin receptor and measure its effect on downstream signal transduction. In mice, κ-CGN treatment reduced weight gain without affecting food intake. Glucose and insulin tolerance tests revealed that κ-CGN treatment increased blood glucose levels and glycosylated hemoglobin levels, while hepatic and muscle glycogen levels were decreased, suggesting that κ-CGN affected glucose metabolism in mice. Interestingly, κ-CGN treatment did not cause typical diabetic symptoms in mice, as indicated by low levels of fasting and postprandial blood glucose, in addition to normal pancreatic tissue and insulin secretion. The binding studies revealed that κ-CGN could competitively bind to the insulin receptor with FITC-insulin and thereby disrupt PI3K and Akt activation, thus suppressing expression of glucose transporters and glycogen synthase. In summary, this study revealed that κ-CGN reduced weight gain without affecting food intake, but impaired glucose metabolism in mice by interfering with insulin binding to receptors, thereby affecting the sensitivity of insulin and inhibiting the insulin PI3K/AKT signaling pathway, causing non-diabetic weight gain reduction.
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http://dx.doi.org/10.1016/j.phrs.2020.105417DOI Listing
March 2021

Interocular Suppression as Revealed by Dichoptic Masking Is Orientation-Dependent and Imbalanced in Amblyopia.

Invest Ophthalmol Vis Sci 2020 12;61(14):28

School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: We investigate the orientation tuning of interocular suppression using a dichoptic masking paradigm in adult controls and amblyopes.

Methods: Fourteen adults with anisometropic or mixed amblyopia and 10 control adults participated in our study. Contrast sensitivity was measured by presenting a target Gabor in the tested eye and mean luminance in the untested eye (monocular) and by presenting a target in the tested eye and a bandpass oriented filtered noise in the other eye (masked). Interocular suppression was defined as the thresholds difference between the monocular and masked conditions for each eye. Interocular suppression was measured under parallel and orthogonal suppression configurations. The peak spatial frequency of the target and mask was 0.25 c/d in experiment 1 (low), 1.31 c/d in experiment 2 (mid), and 6.87 c/d in experiment 3 (high).

Results: The masking suppression induced by the amblyopic eye was less strong than that induced by the fellow eye. The suppression from the fellow eye was similar to that observed in the controls. Interocular suppression under parallel configuration was less strong than under orthogonal configuration in amblyopes at low and mid spatial frequency, but not at high spatial frequency.

Conclusions: We demonstrate that the abnormal interocular masking in amblyopia displays the expected characteristic of orientation selectivity expected of normal controls at low and mid spatial frequency, but not at high spatial frequency. The dichoptic masking imbalance between the eyes of amblyopes results in a net suppression of the amblyopic eye during binocular viewing, modeling clinical suppression.
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http://dx.doi.org/10.1167/iovs.61.14.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774058PMC
December 2020

Direct observation of large electron-phonon interaction effect on phonon heat transport.

Nat Commun 2020 Nov 27;11(1):6040. Epub 2020 Nov 27.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

As a foundational concept in many-body physics, electron-phonon interaction is essential to understanding and manipulating charge and energy flow in various electronic, photonic, and energy conversion devices. While much progress has been made in uncovering how phonons affect electron dynamics, it remains a challenge to directly observe the impact of electrons on phonon transport, especially at environmental temperatures. Here, we probe the effect of charge carriers on phonon heat transport at room temperature, using a modified transient thermal grating technique. By optically exciting electron-hole pairs in a crystalline silicon membrane, we single out the effect of the phonon-carrier interaction. The enhanced phonon scattering by photoexcited free carriers results in a substantial reduction in thermal conductivity on a nanosecond timescale. Our study provides direct experimental evidence of the elusive role of electron-phonon interaction in phonon heat transport, which is important for understanding heat conduction in doped semiconductors. We also highlight the possibility of using light to dynamically control thermal transport via electron-phonon coupling.
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http://dx.doi.org/10.1038/s41467-020-19938-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695728PMC
November 2020