Publications by authors named "Minghui Wang"

426 Publications

Work along Both Lines: The Positive Impact of Work-Based Social Media Use on Job Performance.

Int J Environ Res Public Health 2021 11 4;18(21). Epub 2021 Nov 4.

Institute of Psychology and Behavior, Henan University, Kaifeng 475004, China.

Social media has rapidly become an important tool in organizations and has a significant impact on employees' work and organizational operations. By applying social media to their daily work, employees gain access to important information resources that can help them get things done. Using the conservation of resources theory, this study examines the impact of work resources generated by employees' work-based social media use on work status, as well as job performance. Data were collected from the employees of Internet companies in Henan Province and Shanghai, China. We distributed 519 pairs of questionnaires, and 369 pairs of valid paired questionnaires were returned. To estimate the proposed relationships in the theoretical framework, we used SPSS and MPLUS. The results show that work-based social media use can increase employees' work engagement, which in turn increases task performance, job dedication and interpersonal facilitation. It also reduces the negative effects of work interruptions on task performance and job dedication. Therefore, we conclude the positive effects of work-based social media use on job performance can be achieved by increasing work engagement and by reducing work interruptions.
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http://dx.doi.org/10.3390/ijerph182111578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583286PMC
November 2021

Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease.

Alzheimers Dement 2021 Nov 10. Epub 2021 Nov 10.

Department of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, Icahn Institute of Genomics and Multiscale Biology, New York, New York, USA.

Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and the pathogenesis of AD are poorly understood. In this study, we aim to identify AD-specific metabolomic changes and their potential upstream genetic and transcriptional regulators through an integrative systems biology framework for analyzing genetic, transcriptomic, metabolomic, and proteomic data in AD. Metabolite co-expression network analysis of the blood metabolomic data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) shows short-chain acylcarnitines/amino acids and medium/long-chain acylcarnitines are most associated with AD clinical outcomes, including episodic memory scores and disease severity. Integration of the gene expression data in both the blood from the ADNI and the brain from the Accelerating Medicines Partnership Alzheimer's Disease (AMP-AD) program reveals ABCA1 and CPT1A are involved in the regulation of acylcarnitines and amino acids in AD. Gene co-expression network analysis of the AMP-AD brain RNA-seq data suggests the CPT1A- and ABCA1-centered subnetworks are associated with neuronal system and immune response, respectively. Increased ABCA1 gene expression and adiponectin protein, a regulator of ABCA1, correspond to decreased short-chain acylcarnitines and amines in AD in the ADNI. In summary, our integrated analysis of large-scale multiomics data in AD systematically identifies novel metabolites and their potential regulators in AD and the findings pave a way for not only developing sensitive and specific diagnostic biomarkers for AD but also identifying novel molecular mechanisms of AD pathogenesis.
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http://dx.doi.org/10.1002/alz.12468DOI Listing
November 2021

An integrative approach enables high bioresource utilization and bioethanol production from whole stillage.

Bioresour Technol 2022 Jan 19;343:126153. Epub 2021 Oct 19.

College of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China; SDIC Biotech Investment Co.C Ltd., Beijing 100034, China. Electronic address:

Bioethanol is a major biofuel in industry and mainly produced from corn starch with the dry-mill process. However, one of the remaining challenges is how to economically and efficiently exploit the wasted co-products to further improve ethanol production and generate more valuable chemicals. Here, an integrative approach was developed to efficiently utilize the waste cake for ethanol production, accompanied by protein extraction for feed additives. A high-quality protein feed was produced by the ethanol-alkali extraction method (extraction rate up to 46.91%). Notably, by applying two-step chemoenzymatic strategy, the supernatant and solid recycling yield up to 4.1-, 3.8-, and 154-fold improvements of ethanol, glucose, and xylose production, respectively, comparing to non-pretreatment. Moreover, mass balance analysis found this approach significantly contributed 1.74-4.42% (5.96-15.11 kg/ton dry corn) increase of total ethanol production. The gained knowledge about process design holds the potential transferability for other sustainable biowaste management and bioethanol industry.
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http://dx.doi.org/10.1016/j.biortech.2021.126153DOI Listing
January 2022

Hexokinase 2-driven glycolysis in pericytes activates their contractility leading to tumor blood vessel abnormalities.

Nat Commun 2021 10 14;12(1):6011. Epub 2021 Oct 14.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, China.

Defective pericyte-endothelial cell interaction in tumors leads to a chaotic, poorly organized and dysfunctional vasculature. However, the underlying mechanism behind this is poorly studied. Herein, we develop a method that combines magnetic beads and flow cytometry cell sorting to isolate pericytes from tumors and normal adjacent tissues from patients with non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC). Pericytes from tumors show defective blood vessel supporting functions when comparing to those obtained from normal tissues. Mechanistically, combined proteomics and metabolic flux analysis reveals elevated hexokinase 2(HK2)-driven glycolysis in tumor pericytes, which up-regulates their ROCK2-MLC2 mediated contractility leading to impaired blood vessel supporting function. Clinically, high percentage of HK2 positive pericytes in blood vessels correlates with poor patient overall survival in NSCLC and HCC. Administration of a HK2 inhibitor induces pericyte-MLC2 driven tumor vasculature remodeling leading to enhanced drug delivery and efficacy against tumor growth. Overall, these data suggest that glycolysis in tumor pericytes regulates their blood vessel supporting role.
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http://dx.doi.org/10.1038/s41467-021-26259-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517026PMC
October 2021

extract alleviated acetaminophen-induced rat liver injury via inhibiting oxidative stress and apoptosis based on network pharmacology analysis.

Pharm Biol 2021 Dec;59(1):1378-1387

Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China.

Context: Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury. , a variety of Ramat. (Asteraceae), has potential hepatoprotective effect. However, the mechanism is not clear yet.

Objective: To investigate the hepatoprotective activity and mechanism of flower ethanol extract (BZE) on APAP-induced rats based on network pharmacology.

Materials And Methods: Potential pathways of BZE were predicted by network pharmacology. Male Sprague-Dawley rats were pre-treated with BZE (110, 220 and 440 mg/kg, i.g.) for eight days, and then APAP (800 mg/kg, i.g.) was used to induce liver injury. After 24 h, serum and liver were collected for biochemical detection and western blot measurement.

Results: Network pharmacology indicated that liver-protective effect of BZE was associated with its antioxidant and anti-apoptotic efficacy. APAP-induced liver pathological change was alleviated, and elevated serum AST and ALT were reduced by BZE (440 mg/kg) (from 66.45 to 22.64 U/L and from 59.59 to 17.49 U/L, respectively). BZE (440 mg/kg) reduced the ROS to 65.50%, and upregulated SOD and GSH by 212.92% and 175.38%, respectively. In addition, BZE (440 mg/kg) increased levels of p-AMPK, p-GSK3β, HO-1 and NQO1, ranging from 1.66- to 10.29-fold compared to APAP group, and promoted nuclear translocation of Nrf2. BZE also inhibited apoptosis induced by APAP through the PI3K-Akt pathway and restored the ability of mitochondrial biogenesis.

Discussion And Conclusions: Our study demonstrated that BZE protected rats from APAP-induced liver injury through antioxidant and anti-apoptotic pathways, suggesting BZE could be further developed as a potential liver-protecting agent.
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http://dx.doi.org/10.1080/13880209.2021.1986077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510625PMC
December 2021

SARS-CoV-2 Delta variant infects ACE2 primary human bronchial epithelial cells more efficiently than other variants.

J Med Virol 2021 Oct 1. Epub 2021 Oct 1.

Department of Pathology, Qiqihar Medical University, Qiqihar, China.

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http://dx.doi.org/10.1002/jmv.27372DOI Listing
October 2021

Biosensor-based assay of exosome biomarker for early diagnosis of cancer.

Front Med 2021 Sep 27. Epub 2021 Sep 27.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.

Cancer imposes a severe threat to people's health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.
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http://dx.doi.org/10.1007/s11684-021-0884-zDOI Listing
September 2021

Alteration of Gut Microbiota of a Food-Storing Hibernator, Siberian Chipmunk Tamias sibiricus.

Microb Ecol 2021 Sep 25. Epub 2021 Sep 25.

College of Life Sciences, Qufu Normal University, Qufu, 273165, China.

Hibernation represents a state of fasting because hibernators cease eating in the torpid periods. Therefore, food deprivation during hibernation is expected to modify the gut microbiota of host. However, there are few reports of gut microbiota in food-storing hibernators that feed during the interbout arousals. Here we collected fecal samples of Siberian chipmunk T. sibiricus to character and examine changes in the gut microbiota at various stages relative to hibernation: pre-hibernation, early-hibernation, mid-hibernation, late-hibernation, and post-hibernation. Compared to the pre-hibernation state, alpha-diversity of gut microbiota was significantly increased during the interbout arousal periods. In addition, beta-diversity of the fecal communities from pre-hibernation and interbout arousal periods grouped together, and post-hibernation gut microbiota resembled the counterpart at late-hibernation. Hibernation significantly decreased the relative abundance of Firmicutes but increased Bacteroidetes, reflecting a shift of microbiota toward taxa in favor of host-derived substrates. The increased abundance of Ruminococcaceae_UCG-014, Lactobacillus, and Christensenellaceae_R-7_group in gut microbiota may help the chipmunks reduce intestinal inflammation and then maintain healthy bowel during hibernation. KEGG pathway indicated that hibernation altered the metabolic function of gut microflora of T. sibiricus. Our study provides evidence that the gut microbiota of food-storing hibernators, despite feeding during the interbout arousals, shows similar response to hibernation that has well documented in fat-storing counterparts, suggesting the potential for a core gut microbiota during hibernation of mammals. Importantly, these results will broaden our understanding of the effects of hibernation on gut microbiota of mammal hibernators.
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http://dx.doi.org/10.1007/s00248-021-01877-7DOI Listing
September 2021

Total serum IL-6 and TNF-C levels in children with bronchopneumonia following treatment with methylprednisolone in combination with azithromycin.

Am J Transl Res 2021 15;13(8):9458-9464. Epub 2021 Aug 15.

Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang, China.

Objective: To analyze the expression levels of total serum interleukin (IL)-6 and tumor necrosis factor (TNF)-C in children with bronchopneumonia treated by methylprednisolone in combination with azithromycin.

Methods: Eighty-three children with bronchopneumonia were randomly divided into a test group (TG) and a control group (CG). The TG was comprised of 40 children treated with methylprednisolone combined with azithromycin, whereas the CG was comprised of 43 patients who received methylprednisolone monotherapy. The post-treatment effective rates and occurrence of adverse reactions were compared between the two groups. In addition, the resolution times of symptoms such as fever, cough, moist rale, asthma, and shadow on the lung X-ray were recorded. The levels of the inflammatory factors tumor necrosis factor-C (TNF-C) and interleukin-6 (IL-6) were measured after treatment. The quality of life was evaluated and compared based on the Medical Outcome Study (MOS) 36-Item Short-Form Health Survey (SF-36).

Results: The total effective rate in the TG was significantly higher than that in the CG. The expression levels of TNF-C and IL-6 in the TG were significantly lower than those in the CG. The resolution times of the clinical symptoms were significantly shorter in the TG than in the CG. The ACT (Asthma Control Test) score in the TG was significantly lower than that in the CG. The TG presented with a significantly lower incidence of adverse reactions than that the CG.

Conclusion: The combined administration of methylprednisolone and antibiotics can effectively improve the levels of serum inflammatory factors and the clinical symptoms in children with bronchopneumonia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430067PMC
August 2021

Visual naked-eye detection of SARS-CoV-2 RNA based on covalent organic framework capsules.

Chem Eng J 2022 Feb 11;429:132332. Epub 2021 Sep 11.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, PR China.

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as "naked-eye" detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.
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http://dx.doi.org/10.1016/j.cej.2021.132332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433056PMC
February 2022

Cinnamic Acid Ameliorates Nonalcoholic Fatty Liver Disease by Suppressing Hepatic Lipogenesis and Promoting Fatty Acid Oxidation.

Evid Based Complement Alternat Med 2021 2;2021:9561613. Epub 2021 Sep 2.

Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, China.

Background: Cinnamic acid (CA) has been shown to have many beneficial effects including regulating lipid metabolism and reducing obesity. However, its effect on nonalcoholic fatty liver disease (NAFDL) has not been investigated in detail. Thus, we performed this study in order to explore CA's effect on hepatic lipid metabolism and the underlying mechanisms.

Method: Oleic acid (OA) was used to induce lipid accumulation in HepG2 cells. After coincubation with CA, the cells were stained with oil red O and the triglyceride (TG) content was assessed. Key genes in lipogenesis and fatty acid oxidation pathways were tested. Additionally, db/db and wt/wt mice were divided into three groups, with the wt/wt mice representing the normal group and the db/db mice being divided into the NAFLD and CA groups. After 4 weeks of oral treatment, all mice were sacrificed and the blood lipid profile and liver tissues were assessed.

Results: CA treatment reduced the lipid accumulation in HepG2 cells and in db/db mouse livers. ACLY, ACC, FAS, SCD1, PPAR, and CD36 were significantly downregulated, while CPT1A, PGC1, and PPAR were significantly upregulated.

Conclusion: CA's therapeutic effect on NAFLD may be attributed to its ability to lower hepatic lipid accumulation, which is mediated by suppression of hepatic lipogenesis and fatty acid intake, as well as increased fatty acid oxidation.
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http://dx.doi.org/10.1155/2021/9561613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433026PMC
September 2021

α/Sulfono-γ-AApeptide Hybrid Analogues of Glucagon with Enhanced Stability and Prolonged In Vivo Activity.

J Med Chem 2021 09 10;64(18):13893-13901. Epub 2021 Sep 10.

Department of Chemistry, University of South Florida, Tampa, Florida 33620, United States.

Peptide drugs have the advantages of target specificity and good drugability and have become one of the most increasingly important hotspots in new drug research in biomedical sciences. However, peptide drugs generally have low bioavailability and metabolic stability, and therefore, the modification of existing peptide drugs for the purpose of improving stability and retaining activity is of viable importance. It is known that glucagon is an effective therapy for treating severe hypoglycemia, but its short half-life prevents its wide therapeutic use. Herein, we report that combined unnatural residues and long fatty acid conjugation afford potent α/sulfono-γ-AApeptide hybrid analogues of Glucagon with enhanced stability and prolonged in vivo activity. This strategy could be adopted to develop stabilized analogues of other short-acting bioactive peptides.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01289DOI Listing
September 2021

Semi-HIC: A novel semi-supervised deep learning method for histopathological image classification.

Comput Biol Med 2021 10 21;137:104788. Epub 2021 Aug 21.

School of Information Science and Technology, University of Science and Technology of China, 443 Huangshan Road, Hefei, 230027, China; Research Centers for Biomedical Engineering, University of Science and Technology of China, 443 Huangshan Road, Hefei, 230027, China. Electronic address:

Histopathological images provide a gold standard for cancer recognition and diagnosis. Existing approaches for histopathological image classification are supervised learning methods that demand a large amount of labeled data to obtain satisfying performance, which have to face the challenge of limited data annotation due to prohibitive time cost. To circumvent this shortage, a promising strategy is to design semi-supervised learning methods. Recently, a novel semi-supervised approach called Learning by Association (LA) is proposed, which achieves promising performance in nature image classification. However, there are still great challenges in its application to histopathological image classification due to the wide inter-class similarity and intra-class heterogeneity in histopathological images. To address these issues, we propose a novel semi-supervised deep learning method called Semi-HIC for histopathological image classification. Particularly, we introduce a new semi-supervised loss function combining an association cycle consistency (ACC) loss and a maximal conditional association (MCA) loss, which can take advantage of a large number of unlabeled patches and address the problems of inter-class similarity and intra-class variation in histopathological images, and thereby remarkably improve classification performance for histopathological images. Besides, we employ an efficient network architecture with cascaded Inception blocks (CIBs) to learn rich and discriminative embeddings from patches. Experimental results on both the Bioimaging 2015 challenge dataset and the BACH dataset demonstrate our Semi-HIC method compares favorably with existing deep learning methods for histopathological image classification and consistently outperforms the semi-supervised LA method.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104788DOI Listing
October 2021

L-Citrulline Influences the Body Temperature, Heat Shock Response and Nitric Oxide Regeneration of Broilers Under Thermoneutral and Heat Stress Condition.

Front Physiol 2021 11;12:671691. Epub 2021 Aug 11.

Department of Animal Science, College of Animal Science and Veterinary Medicine, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control, Shandong Agricultural University, Tai'an, China.

Heat stress (HS) adversely affects several physiological responses in organisms, but the underlying molecular mechanisms involved are yet to be fully understood. L-Citrulline (L-Cit) is a nutraceutical amino acid that is gaining research interest for its role in body temperature regulation and nitric oxide synthesis. This study investigated whether dietary supplementation with L-Cit (1% of basal diet) could ameliorate the effects of acute HS on thermotolerance, redox balance, and inflammatory responses of broilers. Ross 308 broilers (288 chicks) were subjected to two environments; thermoneutral at 24°C (TNZ) or HS at 35°C for 5 h, and fed two diets; control or L-Cit. The results showed that HS increased the ear, rectal (RT), and core body (CBT) temperatures of broilers, along with higher respiratory rate. The RT and CBT readings were intermittently affected with time effect, whereas, L-Cit supplementation lowered the mean CBT than the control diet. Antioxidant assays showed that superoxide dismutase was increased during HS, while, catalase was promoted by L-Cit supplementation. In addition, L-Cit induced glutathione peroxidase activity compared to the control diet during HS. Hypothalamic heat shock protein (HSP)-90 was upregulated by HS, but L-Cit downregulated heat shock factor (HSF)-1, and HSP 60 mRNA expressions. HSF 3 mRNA expression was downregulated by L-Cit under TNZ condition. More so, HS increased the plasma nitric oxide (NO) concentration but lowered the total NO synthase (tNOS) activity. In contrast, L-Cit supplementation limited NO production but increased the tNOS activity. Arginase activity was increased in the control fed group during HS but L-Cit supplementation lowered this effect. The NOS-COX pathway was significantly affected under TNZ condition, since L-Cit supplementation downregulated the mRNA expression of iNOS-COX2 in the hypothalamus, and further reduced the serum PGE2 concentration. Together, these data indicates that L-Cit influenced the antioxidant defense, heat shock response and nitric oxide regeneration both under thermoneutral and HS conditions; and that L-Cit may be directly and/or indirectly involved in the central regulation of body temperature.
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http://dx.doi.org/10.3389/fphys.2021.671691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385788PMC
August 2021

Robust Multi-Frame Super-Resolution Based on Adaptive Half-Quadratic Function and Local Structure Tensor Weighted BTV.

Sensors (Basel) 2021 Aug 17;21(16). Epub 2021 Aug 17.

College of Computer Science, Sichuan University, Chengdu 610065, China.

It is difficult to improve image resolution in hardware due to the limitations of technology and too high costs, but most application fields need high resolution images, so super-resolution technology has been produced. This paper mainly uses information redundancy to realize multi-frame super-resolution. In recent years, many researchers have proposed a variety of multi-frame super-resolution methods, but it is very difficult to preserve the image edge and texture details and remove the influence of noise effectively in practical applications. In this paper, a minimum variance method is proposed to select the low resolution images with appropriate quality quickly for super-resolution. The half-quadratic function is used as the loss function to minimize the observation error between the estimated high resolution image and low-resolution images. The function parameter is determined adaptively according to observation errors of each low-resolution image. The combination of a local structure tensor and Bilateral Total Variation (BTV) as image prior knowledge preserves the details of the image and suppresses the noise simultaneously. The experimental results on synthetic data and real data show that our proposed method can better preserve the details of the image than the existing methods.
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http://dx.doi.org/10.3390/s21165533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402259PMC
August 2021

Maternal Gut Dysbiosis Alters Offspring Microbiota and Social Interactions.

Microorganisms 2021 Aug 15;9(8). Epub 2021 Aug 15.

College of Life Sciences, Qufu Normal University, Qufu 273165, China.

Increasing application of antibiotics changes the gut microbiota composition, leading to dysbiosis of the gut microbiota. Although growing evidence suggests the potential role of gut dysbiosis as the cause of neurodevelopmental disorders and behavioral defects, a broad gap of knowledge remains to be narrowed to better understand the exact mechanisms by which maternal gut dysbiosis alters microbiota development and social interactions of offspring. Here, we showed that maternal gut dysbiosis during gestation is a critical determinant of gut microbiota and social interactions off mouse offspring. Gut microbiota of 2-week-old offspring showed significant changes in response to maternal antibiotic treatment. We even detected distinct effects of maternal oral antibiotics on gut microbiota of 14-week-old offspring. Compared to controls, offspring born to antibiotics-treated mothers displayed reduction in sociability and preference for social novelty, suggesting that the altered offspring social behavior was closely linked to dysbiosis of maternal gut microbiota. Our study opens the possibility to better understand the mechanism of how maternal gut microbiota vertically impairs social interactions of offspring in animal models, providing support to the maternal gut microbiota as a potential mediator between offspring microbiota and behaviors.
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http://dx.doi.org/10.3390/microorganisms9081742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401725PMC
August 2021

A deep learning algorithm for automatic detection and classification of acute intracranial hemorrhages in head CT scans.

Neuroimage Clin 2021 Aug 11;32:102785. Epub 2021 Aug 11.

Tencent AI Lab, Shenzhen 518057, China. Electronic address:

Acute Intracranial hemorrhage (ICH) is a life-threatening disease that requires emergency medical attention, which is routinely diagnosed using non-contrast head CT imaging. The diagnostic accuracy of acute ICH on CT varies greatly among radiologists due to the difficulty of interpreting subtle findings and the time pressure associated with the ever-increasing workload. The use of artificial intelligence technology may help automate the process and assist radiologists for more prompt and better decision-making. In this work, we design a deep learning approach that mimics the interpretation process of radiologists, and combines a 2D CNN model and two sequence models to achieve accurate acute ICH detection and subtype classification. Being developed using the extensive 2019-RSNA Brain CT Hemorrhage Challenge dataset with over 25000 CT scans, our deep learning algorithm can accurately classify the acute ICH and its five subtypes with AUCs of 0.988 (ICH), 0.984 (EDH), 0.992 (IPH), 0.996 (IVH), 0.985 (SAH), and 0.983 (SDH), respectively, reaching the accuracy level of expert radiologists. Our method won 1st place among 1345 teams from 75 countries in the RSNA challenge. We have further evaluated our algorithm on two independent external validation datasets with 75 and 491 CT scans, respectively, and our method maintained high AUCs of 0.964 and 0.949 for acute ICH detection. These results have demonstrated the high performance and robust generalization ability of our proposed method, which makes it a useful second-read or triage tool that can facilitate routine clinical applications.
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http://dx.doi.org/10.1016/j.nicl.2021.102785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377493PMC
August 2021

Microstructure and Mechanical Properties of Al-Mg-Si Similar Alloy Laminates Produced by Accumulative Roll Bonding.

Materials (Basel) 2021 Jul 27;14(15). Epub 2021 Jul 27.

Key Laboratory of Automotive Materials Ministry of Education, School of Material Science and Technology, Jilin University, Changchun 130022, China.

As the applications of heterogeneous materials expand, aluminum laminates of similar materials have attracted much attention due to their greater bonding strength and easier recycling. In this work, an alloy design strategy was developed based on accumulative roll bonding (ARB) to produce laminates from similar materials. Twin roll casting (TRC) sheets of the same composition but different cooling rates were used as the starting materials, and they were roll bonded up to three cycles at varying temperatures. EBSD showed that the two TRC sheets deformed in distinct ways during ARB processes at 300 °C. Major recrystallizations were significant after the first cycle on the thin sheet and after the third cycle on the thick sheet. The sheets were subject to subsequent aging for better mechanical properties. TEM observations showed that the size and distribution of nano-precipitations were different between the two sheet sides. These nano-precipitations were found to significantly promote precipitation strengthening, and such a promotive effect was referred to as hetero-deformation induced (HDI) strengthening. Our work provides a new promising method to prepare laminated heterogeneous materials with similar alloy TRC sheets.
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http://dx.doi.org/10.3390/ma14154200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348428PMC
July 2021

How humic acid and Tween80 improve the phenanthrene biodegradation efficiency: Insight from cellular characteristics and quantitative proteomics.

J Hazard Mater 2022 01 21;421:126685. Epub 2021 Jul 21.

College of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210009, People's Republic of China. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are toxic and recalcitrant pollutants, with an urgent need for bioremediation. Systematic biodegradation studies show that surfactant-mediated bioremediation is still poorly understood. Here, we investigated a comprehensive cellular response pattern of the PAH degrading strain B. subtilis ZL09-26 to (non-)green surfactants at the cellular and proteomic levels. Eight characteristic cellular factor investigations and detailed quantitative proteomics analyses were performed to understand the highly enhanced phenanthrene (PHE) degradation efficiency (2.8- to 3-fold improvement) of ZL09-26 by humic acid (HA) or Tween80. The commonly upregulated pathway and proteins (Arginine generation, LacI-family transcriptional regulator, and Lactate dehydrogenase) and various metabolic pathways (such as phenanthrene degradation upstream pathway and central carbon metabolism) jointly govern the change of cellular behaviors and improvement of PHE transport, emulsification, and degradation in a network manner. The obtained molecular knowledge empowers engineers to expand the application of surfactants in the biodegradation of PAHs and other pollutants.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126685DOI Listing
January 2022

Learning rich features with hybrid loss for brain tumor segmentation.

BMC Med Inform Decis Mak 2021 07 30;21(Suppl 2):63. Epub 2021 Jul 30.

School of Information Science and Technology, and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, 230027, China.

Background: Accurately segment the tumor region of MRI images is important for brain tumor diagnosis and radiotherapy planning. At present, manual segmentation is wildly adopted in clinical and there is a strong need for an automatic and objective system to alleviate the workload of radiologists.

Methods: We propose a parallel multi-scale feature fusing architecture to generate rich feature representation for accurate brain tumor segmentation. It comprises two parts: (1) Feature Extraction Network (FEN) for brain tumor feature extraction at different levels and (2) Multi-scale Feature Fusing Network (MSFFN) for merge all different scale features in a parallel manner. In addition, we use two hybrid loss functions to optimize the proposed network for the class imbalance issue.

Results: We validate our method on BRATS 2015, with 0.86, 0.73 and 0.61 in Dice for the three tumor regions (complete, core and enhancing), and the model parameter size is only 6.3 MB. Without any post-processing operations, our method still outperforms published state-of-the-arts methods on the segmentation results of complete tumor regions and obtains competitive performance in another two regions.

Conclusions: The proposed parallel structure can effectively fuse multi-level features to generate rich feature representation for high-resolution results. Moreover, the hybrid loss functions can alleviate the class imbalance issue and guide the training process. The proposed method can be used in other medical segmentation tasks.
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http://dx.doi.org/10.1186/s12911-021-01431-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323198PMC
July 2021

Carboxylated and quaternized lignin enhanced enzymatic hydrolysis of lignocellulose treated by p-toluenesulfonic acid due to improving enzyme activity.

Bioresour Technol 2021 Oct 26;337:125465. Epub 2021 Jun 26.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, No. 2 Xuelin Road, Nanjing 210097, China. Electronic address:

Modificated lignins can affect enzymatic hydrolysis efficiency (EHE) because of changing physicochemical properties of lignin. In this study, carboxylated and quaternized lignin (CQL) and hydroxymethylated lignin (HML) were prepared to explore the effect of lignin modification on cellulase adsorption and EHE of p-toluenesulfonic acid treated corn stover (PCS). The results showed that CQL enhanced EHE of PCS due to the higher β-glucosidase (β-GL) activity, resulting from the formation of CQL-β-GL complexes with a lower binding free energy and the improvement of β-GL conformation made by the binding of CQL and β-GL. However, the drop in EHE due to the addition of HML was consequent on β-GL deactivation that was because the binding site of HML and β-GL overlapped with the carbohydrate binding domain of β-GL, causing the decrease in β-GL activity compared with CQL. This study would help deeply elucidate the effect of modified lignins on EHE and cellulase adsorption.
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http://dx.doi.org/10.1016/j.biortech.2021.125465DOI Listing
October 2021

PhosIDN: an integrated deep neural network for improving protein phosphorylation site prediction by combining sequence and protein-protein interaction information.

Bioinformatics 2021 Jul 28. Epub 2021 Jul 28.

School of Information Science and Technology, University of Science and Technology of China, Hefei AH230027, China.

Motivation: Phosphorylation is one of the most studied post-translational modifications, which plays a pivotal role in various cellular processes. Recently, deep learning methods have achieved great success in prediction of phosphorylation sites, but most of them are based on convolutional neural network that may not capture enough information about long-range dependencies between residues in a protein sequence. In addition, existing deep learning methods only make use of sequence information for predicting phosphorylation sites, and it is highly desirable to develop a deep learning architecture that can combine heterogeneous sequence and protein-protein interaction (PPI) information for more accurate phosphorylation site prediction.

Results: We present a novel integrated deep neural network named PhosIDN, for phosphorylation site prediction by extracting and combining sequence and PPI information. In PhosIDN, a sequence feature encoding sub-network is proposed to capture not only local patterns but also long-range dependencies from protein sequences. Meanwhile, useful PPI features are also extracted in PhosIDN by a PPI feature encoding sub-network adopting a multi-layer deep neural network. Moreover, to effectively combine sequence and PPI information, a heterogeneous feature combination sub-network is introduced to fully exploit the complex associations between sequence and PPI features, and their combined features are used for final prediction. Comprehensive experiment results demonstrate that the proposed PhosIDN significantly improves the prediction performance of phosphorylation sites and compares favorably with existing general and kinase-specific phosphorylation site prediction methods.

Availability: PhosIDN is freely available at https://github.com/ustchangyuanyang/PhosIDN.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab551DOI Listing
July 2021

Portal vein thrombosis associated with high 14-day and 6-week rebleeding in patients after oesophageal variceal band ligation: a retrospective, multicentre, nested case-control study.

Hepatol Int 2021 Oct 22;15(5):1183-1195. Epub 2021 Jul 22.

Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People's Republic of China.

Background And Aims: The association between prognosis of variceal bleeding and portal vein thrombosis (PVT) is unclear. In this multicentre study, we determined the effect of PVT on rebleeding and mortality in patients with acute variceal bleeding (AVB) after oesophageal variceal band ligation (EVL).

Methods: Cirrhotic patients with AVB who had undergone EVL were included. The patients were allocated to either the PVT group or the control cirrhotic group (CCG) based on the presence or absence of PVT. One-year rebleeding episodes and mortality after EVL were recorded.

Results: A total of 218 cirrhotic patients with AVB from 3 centres were included. Patients with PVT had a higher rate of 14-day and 6-week rebleeding than those without PVT (14-day: 8.26% vs. 1.83%, p = 0.03; 6-week: 11.92% vs. 1.83%, p = 0.003). The rates of 5-day failure (3.67% vs. 0.92%, p = 0.175), 1-year rebleeding (21.10% vs. 20.18%, p = 0.867), and 14-day, 6-week, and 1-year mortality were similar between the groups (14-day: 3.67% vs. 0.92%, p = 0.175; 6-week: 3.67% vs. 0.92%, p = 0.175; 1-year: 3.67% vs. 1.83%, p = 0.408). The Child-Pugh class [p = 0.022, hazard ratio (HR): 1.453; 95% confidence interval (CI) 1.056-1.998], PVT (p = 0.050, HR: 4.622, 95% CI 0.999-21.395), albumin < 30 g/L (p = 0.023, HR: 5.886, 95% CI 1.272-27.245), and number of bands (p = 0.010, HR: 1.207, 95% CI 1.046-1.393) were identified as the predictors for 14-day rebleeding; the multivariate analysis revealed only the number of bands (p = 0.009, HR: 1.247, 95% CI 1.056-1.473) as the independent factor. PVT (p = 0.012, HR: 6.732, 95% CI 1.519-29.835) and albumin < 30 g/L (p = 0.027, HR: 3.643, 95% CI 1.160-11.441) were identified as predictors for 6-week rebleeding; however, only PVT (p = 0.015, HR: 6.380, 95% CI 1.427-28.515) was found to be the independent factor in the multivariate analysis. Further analysis showed that superior mesenteric vein (SMV) thrombosis is the only risk factor predicting 6-week rebleeding in patients with PVT (p = 0.032, HR: 3.405, 95% CI 1.112-10.429).

Conclusions: PVT was associated with high 14-day and 6-week rebleeding in patients after EVL. SMV thrombosis was the only risk factor for 6-week rebleeding in patients with PVT. High albumin levels may serve as a protective factor for the 14-day and 6-week rebleeding risk. PVT was not responsible for mortality after EVL during 1-year follow-up.
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http://dx.doi.org/10.1007/s12072-021-10224-4DOI Listing
October 2021

Circulating lncRNA UCA1 and lncRNA PGM5-AS1 act as potential diagnostic biomarkers for early-stage colorectal cancer.

Biosci Rep 2021 07;41(7)

Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, China.

Background: Colorectal cancer (CRC) is one of the most common and significant malignant diseases worldwide. In the present study, we evaluated two long non-coding RNAs (lncRNAs) in CRC patients as diagnostic markers for early-stage CRC.

Methods: Using Gene Expression Omnibus (GEO) datasets GSE102340, GSE126092, GSE109454 and GSE115856, 14 differentially expressed lncRNAs were identified between cancer and adjacent tissues, among which, the two most differentially expressed were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR) in 200 healthy controls and 188 CRC patients. A receiver operating characteristic (ROC) analysis was employed to evaluate the diagnostic accuracy for CRC.

Results: From four GEO datasets, three up-regulated and eleven down-regulated lncRNAs were identified in CRC tissues, among which, lncRNA urothelial carcinoma-associated 1 (UCA1) and lncRNA phosphoglucomutase 5-antisense RNA 1 (PGM5-AS1) were the most significantly up- and down-regulated lncRNAs in CRC patient plasma, respectively. The area under the ROC curve was calculated to be 0.766, 0.754 and 0.798 for UCA1, PGM5-AS1 and the combination of these two lncRNAs, respectively. Moreover, the diagnostic potential of these two lncRNAs was even higher for the early stages of CRC. The combination of UCA1 and PGM5-AS1 enhanced the AUC to 0.832, and when the lncRNAs were used with carcinoembryonic antigen (CEA), the AUC was further improved to 0.874.

Conclusion: In the present study, we identified two lncRNAs, UCA1 and PGM5-AS1, in CRC patients' plasma, which have the potential to be used as diagnostic biomarkers of CRC.
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http://dx.doi.org/10.1042/BSR20211115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276091PMC
July 2021

Solvent-free microwave synthesis of ultra-small [email protected] with strong metal-support interaction for industrial hydrogen evolution.

Nat Commun 2021 Jun 29;12(1):4018. Epub 2021 Jun 29.

Key Laboratory of Eco-chemical Engineering, Key Laboratory of Optic-electric Sensing and Analytical Chemistry of Life Science, Taishan Scholar Advantage and Characteristic Discipline Team of Eco Chemical Process and Technology, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, P. R. China.

Exploring a simple, fast, solvent-free synthetic method for large-scale preparation of cheap, highly active electrocatalysts for industrial hydrogen evolution reaction is one of the most promising work today. In this work, a simple, fast and solvent-free microwave pyrolysis method is used to synthesize ultra-small (3.5 nm) [email protected] catalyst with heterogeneous structure and strong metal-support interaction in one step. The [email protected] catalyst only exhibits an overpotential of 15 mV at a current density of 10 mA cm, and exhibits a large turnover frequency value up to 21.9 s under an overpotential of 100 mV in 1.0 M KOH. In addition, this catalyst can reach high current densities of 500 mA cm and 1000 mA cm at low overpotentials of 56 mV and 78 mV respectively, and it displays high stability of 1000 h. This work provides a feasible way for the reasonable design of other large-scale production catalysts.
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http://dx.doi.org/10.1038/s41467-021-24322-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242096PMC
June 2021

A robust CRISPR-Cas12a biosensor coated with metal-organic framework.

J Mater Chem B 2021 07;9(27):5451-5455

Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China. and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

Metal-organic frameworks (MOFs) are proposed to protect a CRISPR-associated enzyme/RNA complex from harsh environments, while the complex can be quickly released from MOFs with high efficiency. Therefore, the application of CRISPR-powered biosensing can be more feasible.
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http://dx.doi.org/10.1039/d1tb01126jDOI Listing
July 2021

PEX5 prevents cardiomyocyte hypertrophy via suppressing the redox-sensitive signaling pathways MAPKs and STAT3.

Eur J Pharmacol 2021 Sep 24;906:174283. Epub 2021 Jun 24.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences; National and Local United Engineering Lab of Druggability and New Drugs Evaluation; Guangdong Engineering Laboratory of Druggability and New Drug Evaluation; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, China. Electronic address:

Peroxisomal biogenesis factor 5 (PEX5) is a member of peroxisome biogenesis protein family which serves as a shuttle receptor for the import of peroxisome matrix protein. The function of PEX5 on cardiomyocyte hypertrophy remained to be elucidated. Our study demonstrated that the protein expression level of PEX5 was declined in primary neonatal rat cardiomyocytes treated with phenylephrine (PE) and hearts from cardiac hypertrophic rats induced by abdominal aortic constriction (AAC). Overexpression of PEX5 alleviated cardiomyocyte hypertrophy induced by PE, while silencing of PEX5 exacerbated cardiomyocyte hypertrophy. PEX5 improved redox imbalance by decreasing cellular reactive oxygen species level and preserving peroxisomal catalase. Moreover, PEX5 knockdown aggravated PE-induced activation of redox-sensitive signaling pathways, including mitogen-activated protein kinase (MAPK) pathway and signal transducer and activator of transcription 3 (STAT3); whereas PEX5 overexpression suppressed activation of MAPK and STAT3. But PEX5 did not affect PE-induced phosphorylation of mammalian target of rapamycin (mTOR). In conclusion, the present study suggests that PEX5 protects cardiomyocyte against hypertrophy via regulating redox homeostasis and inhibiting redox-sensitive signaling pathways MAPK and STAT3.
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http://dx.doi.org/10.1016/j.ejphar.2021.174283DOI Listing
September 2021

Electrochemical Deposition of Cu Metal-Organic Framework Films for the Dual Analysis of Pathogens.

Anal Chem 2021 06 21;93(25):8994-9001. Epub 2021 Jun 21.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

Metal-organic framework (MOF) thin films with flexible nature and prominent qualities have opened doors to new technological applications in different fields. Herein, we propose an electrochemical biosensor for the dual detection of Staphylococcus aureus based on the electrodeposition of Cu metal-organic framework (Cu-MOF) thin films. The promising sensing layer with features of good electronic conductivity and enhanced electron-transfer property can not only identify through specific micrococcal nucleases in the supernatant but also detect the pathogen directly aptamer recognition. The dual analysis design ensures the accuracy of this method for detection in the range of 7-7 × 10 cfu/mL with the limits of detection of 1.9 and 5.2 cfu/mL. Moreover, the analytical method validation confirmed that the biosensor could efficiently work in complex biological samples, showing good selectivity and specificity and great potential for clinical diagnosis. More importantly, the current proposed strategy is simple and easy to implement without the need for extra signaling elements, which is convenient for timely clinical detection.
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http://dx.doi.org/10.1021/acs.analchem.1c01763DOI Listing
June 2021

Chronic Intermittent Hypoxia Enhances Pathological Tau Seeding, Propagation, and Accumulation and Exacerbates Alzheimer-like Memory and Synaptic Plasticity Deficits and Molecular Signatures.

Biol Psychiatry 2021 Mar 24. Epub 2021 Mar 24.

Department of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Obstructive sleep apnea, characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), is a risk factor for Alzheimer's disease (AD) progression. Recent epidemiological studies point to CIH as the best predictor of developing cognitive decline and AD in older adults with obstructive sleep apnea. However, the precise underlying mechanisms remain unknown. This study was undertaken to evaluate the effect of CIH on pathological human tau seeding, propagation, and accumulation; cognition; synaptic plasticity; neuronal network excitability; and gene expression profiles in a P301S human mutant tau mouse model of AD and related tauopathies.

Methods: We exposed 4- to 4.5-month-old male P301S and wild-type mice to an 8-week CIH protocol (6-min cycle: 21% O to 8% O to 21% O, 80 cycles per 8 hours during daytime) and assessed its effect on tau pathology and various AD-related phenotypic and molecular signatures. Age- and sex-matched P301S and wild-type mice were reared in normoxia (21% O) as experimental controls.

Results: CIH significantly enhanced pathological human tau seeding and spread across connected brain circuitry in P301S mice; it also increased phosphorylated tau load. CIH also exacerbated memory and synaptic plasticity deficits in P301S mice. However, CIH had no effect on seizure susceptibility and network hyperexcitability in these mice. Finally, CIH exacerbated AD-related pathogenic molecular signaling in P301S mice.

Conclusions: CIH-induced increase in pathologic human tau seeding and spread and exacerbation of other AD-related impairments provide new insights into the role of CIH and obstructive sleep apnea in AD pathogenesis.
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http://dx.doi.org/10.1016/j.biopsych.2021.02.973DOI Listing
March 2021
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