Publications by authors named "Hai Yang"

273 Publications

Effect of High Cholesterol Regulation of LRP1 and RAGE on Aβ Transport Across the Blood-brain Barrier in Alzheimer's Disease.

Curr Alzheimer Res 2021 Sep 5. Epub 2021 Sep 5.

Department of Neurology, Daping Hospital, Army Medical University, Chongqing400042. China.

Background: High cholesterol aggravates the risk development of Alzheimer's disease (AD). AD is closely related to the transport impairment of amyloid-β (Aβ) in the blood-brain barrier. It is unclear whether high cholesterol affects the risk of cognitive impairment in AD by affecting Aβ transport. The purpose of the study is to investigate whether high cholesterol regulates Aβ transport through low-density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) in the risk development of AD.

Methods: We established high cholesterol AD mice model. The learning and memory functions were evaluated by Morris water maze (MWM). Cerebral microvascular endothelial cells were isolated, cultured, and observed. The expression levels of LRP1 and RAGE of endothelial cells and their effect on Aβ transport in vivo were observed. The expression level of LRP1 and RAGE was detected in cultured microvessels after using Wnt inhibitor DKK-1 and β-catenin inhibitor XAV-939.

Results: Hypercholesterolemia exacerbated spatial learning and memory impairment. Hypercholes- terolemia increased serum Aβ40 level, while serum Aβ42 level did not change significantly. Hyper- cholesterolemia decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells. Hypercholesterolemia increased brain apoptosis in AD mice. In in vitro experiment, high cholesterol decreased LRP1 expression and increased RAGE expression, increased Aβ40 expression in cerebral microvascular endothelial cells. High cholesterol regulated the expressions of LRP1 and RAGE and transcriptional activity of LRP1 and RAGE promoters by the Wnt/β-catenin signaling pathway.

Conclusion: High cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aβ transport disorder in the blood-brain barrier. Increased Aβ deposition in the brain aggravated apoptosis in the brain, resulting to cognitive impairment of AD mice.
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http://dx.doi.org/10.2174/1567205018666210906092940DOI Listing
September 2021

Restrictive versus liberal transfusion thresholds in very low birth weight infants: A systematic review with meta-analysis.

PLoS One 2021 30;16(8):e0256810. Epub 2021 Aug 30.

Affiliated Hospital & Clinical Medical College of Chengdu University, Chengdu, Sichuan, China.

Background: To assess the efficacy and safety of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants.

Methods: We searched MEDLINE, EMBASE, and Cochrane database without any language restrictions. The last search was conducted in August 15, 2020. All randomized controlled trials comparing the use of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight (VLBW) infants were selected. Pooled risk ratio (RR) for dichotomous variable with 95% confidence intervals were assessed by a random-effects model. The primary outcome was all-cause mortality.

Results: Overall, this meta-analysis included 6 randomized controlled trials comprising 3,483 participants. Restrictive transfusion does not increase the risk of all-cause mortality (RR, 0.99; 95% CI, 0.84 to 1.17; I2 = 0%; high-quality evidence), and does not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01, 95% CI, 0.93-1.09; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume.

Conclusions: In very low birth weight infants, a restrictive threshold for red blood cell transfusion was not associated with increased risk of all-cause mortality, in either short term or long term.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405031PMC
August 2021

Meta-analysis and systematic review of contrast-enhanced ultrasound in evaluating the treatment response after locoregional therapy of hepatocellular carcinoma.

Abdom Radiol (NY) 2021 Aug 19. Epub 2021 Aug 19.

Department of Radiology, Thomas Jefferson University, 132 South 10th Street, 763G Main Building, Philadelphia, PA, 19107, USA.

Purpose: Contrast-enhanced ultrasound (CEUS) is a useful tool to assess treatment response after percutaneous ablation or transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Here, we performed a systematic review and meta-analysis to evaluate the usefulness of CEUS in identifying residual tumor after locoregional therapy.

Methods: PubMed, Scopus, and Cochrane library databases were searched from their inception until March 8, 2021, for diagnostic test accuracy studies comparing CEUS to a reference standard for identifying residual tumors after locoregional therapy of HCC. The pooled sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were obtained using a bivariate random effects model. Subgroup analyses were performed by stratifying the studies based on study design, type of locoregional therapy, CEUS criteria for residual tumor, timing of CEUS follow up, and type of standard reference.

Results: Two reviewers independently evaluated 1479 publications. After full-text review, 142 studies were found to be relevant, and 43 publications (50 cohorts) were finally included. The overall sensitivity of CEUS in detection of residual disease estimated from the bivariate random effects model was 0.85 (95% CI 0.80-0.89). Similarly, the overall specificity was 0.94 (95% CI 0.91-0.96). The diagnostic accuracy was 93.5%. The DOR was 70.1 (95% CI 62.2-148), and the AUROC was 0.95. Importantly, subgroup analysis showed no apparent differences in the diagnostic performance between locoregional therapy (TACE vs. ablation) and criteria used to define residual enhancement, timing of performing CEUS, study design, or type of reference standard.

Conclusion: CEUS is a highly accurate method to identify HCC residual tumor after TACE or percutaneous ablation.
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http://dx.doi.org/10.1007/s00261-021-03248-9DOI Listing
August 2021

Overexpression of ASMT likely enhances the resistance of transgenic sheep to brucellosis by influencing immune-related signaling pathways and gut microbiota.

FASEB J 2021 09;35(9):e21783

Beijing Key Laboratory of Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Melatonin is a pleiotropic molecule with a variety of biological functions, which include its immunoregulatory action in mammals. Brucellosis is a worldwide endemic zoonotic disease caused by the Brucella, which not only causes huge economic losses for the livestock industry but also impacts human health. To target this problem, in current study, two marker-free transgenic sheep overexpressing melatonin synthetic enzyme ASMT (acetylserotonin O-methyltransferase) gene were generated and these melatonin enrich transgenic sheep were challenged by Brucella infection. The results showed that the serum melatonin concentration was significantly higher in transgenic sheep than that of wild type (726.92 ± 70.6074 vs 263.10 ± 34.60 pg/mL, P < .05). Brucella challenge test showed that two thirds (4/6) of the wild-type sheep had brucellosis, while none of the transgenic sheep were infected. Whole-blood RNA-seq results showed that differential expression genes (DEGs) were significantly enriched in natural killer cell-mediated cytotoxicity, phagosome, antigen processing, and presentation signaling pathways in overexpression sheep. The DEGs of toll-like receptors (TLRs) and NOD-like receptors (NLRs) families were verified by qPCR and it showed that TLR1, TLR2, TLR7, CD14, NAIP, and CXCL8 expression levels in overexpression sheep were significantly higher and NLRP1, NLRP3, and TNF expression levels were significantly lower than those of wild type. The rectal feces were subjected to 16S rDNA amplicon sequencing, and the microbial functional analysis showed that the transgenic sheep had significantly lower abundance of microbial genes related to infectious diseases compared to the wild type, indicating overexpression animals are likely more resistant to infectious diseases than wild type. Furthermore, exogenous melatonin treatment relieved brucellosis inflammation by upregulating anti-inflammatory cytokines IL-4 and downregulating pro-inflammatory IL-2, IL-6, and IFN-γ. Our preliminary results provide an informative reference for the study of the relationship between melatonin and brucellosis.
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http://dx.doi.org/10.1096/fj.202100651RDOI Listing
September 2021

Comprehensive analysis and expression profiles of cassava UDP-glycosyltransferases (UGT) family reveal their involvement in development and stress responses in cassava.

Genomics 2021 Sep 6;113(5):3415-3429. Epub 2021 Aug 6.

Hainan Key Laboratory for Biosafety Monitoring and Molecular Breeding in Off-Season Reproduction Regions, Key Laboratory of Biology and Genetic Resources of Tropical Crops, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, China; Hainan Key Laboratory for Protection and Utilization of Tropical Bioresources, Hainan Institute for Tropical Agricultural Resources, Chinese Academy of Tropical Agricultural Sciences, Haikou, China; Sanya Research Institute of Chinese Academy of Tropical Agricultural Sciences, Sanya, Hainan, China,. Electronic address:

UDP-glycosyltransferases (UGTs) are widely involved in plant growth and stress responses. However, UGT family are not well understood in cassava. Here, we identified 121 MeUGT genes and classified them into 14 subfamilies by phylogenetic analysis. All MeUGT proteins have typical feature of the UGTs family. Tandem duplications are the crucial driving force for the expansion of MeUGT family. Cis-Acting elements analysis uncovered those 14 kinds of cis-elements associated with biotic and abiotic stress responses. Transcriptomic and qRT-PCR analyses indicated that MeUGT genes participate in postharvest physiological deterioration of storage root and the responses of biotic and abiotic stresses. Of which, MeUGT-14/41 were significantly induced after Xam treatment. Silencing of MeUGT-14 or MeUGT-41 reduced cassava resistance to Xam, verifying the accuracy of transcriptomic data for function prediction. Together, this study characterized the MeUGTs family and revealed their potential functions, which build a solid foundation for MeUGTs associated genetic improvement of cassava.
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http://dx.doi.org/10.1016/j.ygeno.2021.08.004DOI Listing
September 2021

Theoretical Insights into Potential-Dependent C-C Bond Formation Mechanisms during CO Electroreduction into C Products on Cu(100) at Simulated Electrochemical Interfaces.

ACS Omega 2021 Jul 6;6(28):17839-17847. Epub 2021 Jul 6.

Hunan Province Cooperative Innovation Center for the Construction & Development of Dongting Lake Ecologic Economic Zone, Hunan Provincial Key Laboratory of Water Treatment Functional Materials, Hunan Province Engineering Research Center of Electroplating Wastewater Reuse Technology, College of Chemistry and Materials Engineering, Hunan University of Arts and Science, Changde 415000, China.

An improved CO coverage-dependent electrochemical interface model with an explicit solvent effect on Cu(100) is presented in this paper, by which theoretical insights into the potential-dependent C-C bond formation pathways occurring in CO electrochemical reduction to C products can be obtained. Our present studies indicate that CHO is a crucial intermediate toward C products on Cu(111), and dimer OCCO is found to not be a viable species for the production of C products on Cu(100). The reaction pathway of CHO with CO and CHO dimerization into dimers COCHO and CHOCHO may be C-C bond formation mechanisms at low overpotential. However, at medium overpotential, C-C bond coupling takes place preferentially through the reaction of COH with CO species and COH dimerization into dimers COCOH and COHCOH. The formed dimers COCHO, CHOCOH, and CHOCHO reactions of CHO with CO, COH, and CHO species may lead to C products, which are regarded as C-C bond formation mechanisms at high overpotential. The difference of obtained adsorption isotherms of CO on Cu(100) with that of Cu(111) may be able to explain the effect of the crystal face of Cu on product selectivity. The excellent consistencies between our present obtained conclusions and the available experimental reports and partial theoretical studies validate the reasonability of the present employed methodology, which can be also used to systematically study potential-dependent CO electroreduction pathways toward C products on Cu(100) or other metal catalysts.
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http://dx.doi.org/10.1021/acsomega.1c01062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296003PMC
July 2021

An Experimental Study of Clogging Recovery Measures for Ceramic Permeable Bricks.

Materials (Basel) 2021 Jul 13;14(14). Epub 2021 Jul 13.

College of Civil Engineering, Nanjing Forestry University, Nanjing 210037, China.

To explore the best clogging restoration measures for ceramic permeable bricks, ceramic permeable bricks were accurately clogged using a self-designed device by controlling the permeability, and different technical measures were adopted to restore the permeability. Then, the recovery effect, operating parameters and pore change inside the bricks using pressure washing were further discussed. The results showed that pressure washing was the best recovery measure, the joint methods was not recommended due to performance to price ratio. It was necessary to conduct pressure washing in relatively moist conditions, increase the cleaning frequency or prolong the cleaning time in the case of no serious blockage. Hydraulic cleaning can not only increase isolated pores but also remove the trapped solid particles, and increase the proportion of connected pores and dredges through water channels. This research offers some reference for the daily maintenance of permeable bricks.
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http://dx.doi.org/10.3390/ma14143904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304040PMC
July 2021

Association of Chronic Liver Disease and Mortality in Patients With Aneurysmal Subarachnoid Hemorrhage.

Stroke 2021 Jul 20:STROKEAHA121034136. Epub 2021 Jul 20.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China (Y.Z., L.L., L.J., C.Y., Y.C., F.F.).

Background And Purpose: Chronic liver disease (CLD) is a risk factor for increased morbidity and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between CLD and mortality remains unknown.

Methods: In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2009 and 2019. The primary outcome was in-hospital all-cause mortality.

Results: This study included 6228 cases of aSAH, 489 (7.9%) of whom also had CLD. In a propensity-matched analysis, CLD was associated with increased mortality in patients with aSAH compared with non-CLD (odds ratio, 2.04 [95% CI, 1.43-2.92]). In aSAH patients with CLD, a high Model for End-Stage Liver Disease score was still associated with an increased odds of mortality.

Conclusions: Among aSAH patients, CLD was associated with increased mortality compared with non-CLD. Among aSAH patients with CLD, a higher Model for End-Stage Liver Disease score was associated with an increased odds of mortality.
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http://dx.doi.org/10.1161/STROKEAHA.121.034136DOI Listing
July 2021

Network Meta-Analysis: Noninvasive Imaging Modalities for Identifying Clinically Significant Portal Hypertension.

Dig Dis Sci 2021 Jul 17. Epub 2021 Jul 17.

Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Suite 763 H, Main Building, Philadelphia, PA, 19107, USA.

Background: Although measurement of the hepatic venous pressure gradient (HVPG) is the current reference standard for obtaining portal venous pressures, several noninvasive imaging-based modalities have been proposed as alternatives.

Aims: We performed a systematic review and meta-analysis to compare the diagnostic accuracy of noninvasive imaging approaches for identifying clinically significant portal hypertension (CSPH).

Methods: Two independent reviewers conducted a literature search of PubMed, SCOPUS, and the Cochrane Library from inception until January 5, 2021. The following imaging modalities were compared to HVPG: computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance elastography, ultrasound, transient elastography (TE), shear wave elastography (SWE), acoustic radiation force impulse (ARFI) imaging, contrast-enhanced ultrasound (CEUS), and subharmonic-aided pressure estimation (SHAPE). Sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for summary receiver operating characteristic were calculated using both frequentist random effects and Bayesian network meta-analytic approaches.

Results: We analyzed 45 studies of 5678 patients. A broad overlapping confidence interval (CI) of DOR was observed among different imaging modalities: ARFI (30.5; 95% CI 12.7-73.3), CEUS and SHAPE (21.1; 95% CI 6.4-69.8), TE of liver stiffness (21.1; 95% CI 13.3-33.5), CT and MRI (13.7; 95% CI 7.40-25.4), SWE of liver stiffness (10.5; 95% CI 5.2-21.1), and ultrasound (9.5; 95% CI 4.9-18.4). The AUC of all imaging methods exceeded 0.8, indicating very good performance. At a cutoff of 80% specificity, TE, CEUS, and SHAPE exceeded 80% sensitivity.

Conclusion: Overall, noninvasive imaging modalities perform well for identifying CSPH. Clinicians should consider these noninvasive and cost-efficient tests when diagnosing CSPH.
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http://dx.doi.org/10.1007/s10620-021-07168-yDOI Listing
July 2021

Full-scale municipal sludge pyrolysis in China: Design fundamentals, environmental and economic assessments, and future perspectives.

Sci Total Environ 2021 Nov 2;795:148832. Epub 2021 Jul 2.

Wuhan Pro-Envi Tech Co., Ltd, Wuhan, Hubei 430062, China.

The increasing amount of municipal sludge in China requires safe and effective management to protect human health and ensure environmental sustainability. Pyrolysis is a thermochemical process that decomposes organic matter at elevated temperature and under anaerobic conditions, and it has attracted an increasing attention in sludge treatment in the recent years. However, comprehensive environmental and economic assessment of sludge pyrolysis in China's context is rare, due to the small quantities of full-scale sludge pyrolysis plant. In this paper, we applied our design and operation parameters of full-scale sludge pyrolysis plants to generate the material and energy consumptions of the pyrolysis system under various of conditions, including sludge organic content and moisture content, system size, system energy distribution, and whether or not heat substitution is applied. Life cycle assessment and techno-economic assessment were then applied to investigate the environmental and economic performance of the system. Our results demonstrate the significant environmental and economic impacts associated with sludge properties and system size. Generally, sludge with higher organic content and lower moisture content requires less natural gas consumption, which leads to a simultaneous improvement of the system environmental and economic performance. The system economic performance is more sensitive to the system size, and centralized sludge handling using a larger pyrolysis system is more economic favorable. In the most ideal case, the average global warming potential and minimum sludge handling price of sludge pyrolysis could be as low as -32.5 kg CO-Eq/t DS and 188.8 $/t DS, respectively. Based on these results, we discussed the pathways that could be taken to further optimize the environmental and economic performances of the pyrolysis system.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148832DOI Listing
November 2021

Eleven routine clinical features predict COVID-19 severity uncovered by machine learning of longitudinal measurements.

Comput Struct Biotechnol J 2021 17;19:3640-3649. Epub 2021 Jun 17.

Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China.

Severity prediction of COVID-19 remains one of the major clinical challenges for the ongoing pandemic. Here, we have recruited a 144 COVID-19 patient cohort, resulting in a data matrix containing 3,065 readings for 124 types of measurements over 52 days. A machine learning model was established to predict the disease progression based on the cohort consisting of training, validation, and internal test sets. A panel of eleven routine clinical factors constructed a classifier for COVID-19 severity prediction, achieving accuracy of over 98% in the discovery set. Validation of the model in an independent cohort containing 25 patients achieved accuracy of 80%. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.70, 0.99, 0.93, and 0.93, respectively. Our model captured predictive dynamics of lactate dehydrogenase (LDH) and creatine kinase (CK) while their levels were in the normal range. This model is accessible at https://www.guomics.com/covidAI/ for research purpose.
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http://dx.doi.org/10.1016/j.csbj.2021.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225590PMC
June 2021

A new basic thoracoscopic surgical skill training and assessment system using automatic scoring techniques.

Surg Endosc 2021 Jun 24. Epub 2021 Jun 24.

Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, China.

Purpose: We report a new thoracoscopic surgical skill training and assessment system with automatic scoring techniques, the Huaxi Intelligent Thoracoscopic Skill Training and Assessment (HITSTA) system. We also evaluated the discriminative ability of this system compared to our conventional scoring method at our institution.

Methods: We retrospectively collected training data of thoracic board-certified thoracic surgeons at West China Hospital, Sichuan University from January 1, 2018 to January 1, 2019. Surgeons were assessed by HITSTA system and human examiners simultaneously. Total scores were summed from 3 tasks (grasping with delivery, pattern cutting, and suture with knot). Bland-Altman analysis was used to test agreement of scores made by HITSTA system (automatic scoring) and human examiners (manual scoring). Differentiation ability was also compared between the two scoring methods.

Results: Thirty-nine surgeons were recruited. Scores made by HITSTA system and human examiners were not consistent. For suture with knot, automatic scoring method could detect the score differences between different training status (trained: 26.92 ± 12.04, untrained: 19.85 ± 11.12; p = 0.026) and training duration (< 10 h: 20.67 ± 15.23,  ≥ 10 h: 31.92 ± 5.56; p = 0.003). For total scores, automatic scoring approach could discriminate between different training status (trained: 71.90 ± 12.63; untrained: 61.41 ± 13.87; p = 0.016) and training duration (< 10 h: 65.23 ± 15.31;  ≥ 10 h 77.23 ± 6.94; p = 0.046).

Conclusion: HITSTA system could discriminate the different levels of thoracoscopic surgical skills better than the traditional manual scoring method. Larger prospective studies are warranted to validate the differentiation ability of HITSTA system.
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http://dx.doi.org/10.1007/s00464-021-08606-8DOI Listing
June 2021

Neutrophil Counts as Promising Marker for Predicting In-Hospital Mortality in Aneurysmal Subarachnoid Hemorrhage.

Stroke 2021 Jun 25:STROKEAHA120034024. Epub 2021 Jun 25.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China (Y.Z., L.L., X.C., Younian Chen, X.W., C.Y., Yongzhong Cheng, F.F.).

Background And Purpose: Systemic inflammation is recognized as a hallmark of stroke. We aimed to evaluate the prognostic value of various inflammatory factors using blood at admission in patients with aneurysmal subarachnoid hemorrhage.

Methods: In a multicenter observational study of patients with aneurysmal subarachnoid hemorrhage, the counts of neutrophil, platelet, and lymphocyte were collected on admission. Patients were stratified based on neutrophil counts with propensity score matching to minimize confounding. We calculated the adjusted odds ratios with 95% CIs for the primary outcome of in-hospital mortality and hospital-acquired infections.

Results: A total of 6041 patients were included in this study and 344(5.7%) of them died in hospital. Propensity score matching analyses indicated that compared with the lower neutrophil counts, higher neutrophil counts were associated with increased risk of in-hospital mortality (odds ratio, 1.53 [95% CI, 1.14-2.06]), hospital-acquired infections (odds ratio, 1.61 [95% CI, 1.38-1.79]), and delayed neurological ischemic deficits (odds ratio, 1.52 [95% CI, 1.09-1.97]). Moreover, out of all the inflammatory factors studied, neutrophil counts demonstrated the highest correlation with in-hospital mortality and hospital-acquired infections.

Conclusions: Among patients with aneurysmal subarachnoid hemorrhage, high neutrophil counts at admission were associated with increased mortality and hospital-acquired infections. The neutrophil count is a simple, useful marker with prognostic value in patients with aneurysmal subarachnoid hemorrhage.
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http://dx.doi.org/10.1161/STROKEAHA.120.034024DOI Listing
June 2021

Fungal siderophore biosynthesis catalysed by an iterative nonribosomal peptide synthetase.

Chem Sci 2020 Sep 28;11(42):11525-11530. Epub 2020 Sep 28.

Department of Chemical and Biomolecular Engineering, University of California Los Angeles California 90095 USA

Siderophores play a vital role in the viability of fungi and are essential for the virulence of many pathogenic fungal species. Despite their importance in fungal physiology and pathogenesis, the programming rule of siderophore assembly by fungal nonribosomal peptide synthetases (NRPSs) remains unresolved. Here, we report the characterization of the bimodular fungal NRPS, SidD, responsible for construction of the extracellular siderophore fusarinine C. The use of intact protein mass spectrometry, together with biochemical assays of native and dissected enzymes, provided snapshots of individual biosynthetic steps during NPRS catalysis. The adenylation and condensation domain of SidD can iteratively load and condense the amino acid building block -AMHO, respectively, to synthesize fusarinine C. Our study showcases the iterative programming features of fungal siderophore-producing NRPSs.
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http://dx.doi.org/10.1039/d0sc03627gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162485PMC
September 2020

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Evaluation of sleep disorder in orthopedic trauma patients: a retrospective analysis of 1129 cases.

J Orthop Surg Res 2021 May 29;16(1):344. Epub 2021 May 29.

Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China.

Background: In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder.

Methods: All orthopedic trauma patients confined in a trauma ward in West China Hospital of Sichuan University between April 2018 and July 2019 were included in this retrospective study. Patients with mental impairment or craniocerebral injuries were excluded from the study. Basic demographic data and the Injury Severity Score (ISS) classification based on medical records were collected. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, the visual analog scale (VAS) was used to evaluate physical pain, and the Barthel Index (BI) was used to evaluate activities of daily living (ADL). Univariate linear regression analysis and multivariate linear regression analysis were used to identify independently related factors.

Results: The average PSQI score was 6.3 (± 4.0). A total of 581 (51.4%) patients had a PSQI score > 5, indicating the presence of sleep disorders. The PSQI score was > 10 in 174 (15.4%) patients. Univariate statistical analysis showed that age, sex, education, ADL, and ISS classification were associated with increased PSQI scores. Marital status and pain were not associated with increased PSQI scores. When we used multivariate analysis to control for confounding variables, sex, ADL, and ISS classification remained independently associated with PSQI (P = 0.002, < 0.000, and 0.002, respectively).

Conclusions: In our study, sleep disorders were common (51.4% with PSQI > 5) and serious (15.4% with PSQI > 10) in patients with traumatic orthopedic injury. The following factors were closely associated with sleep disorders: sex, ADL, and ISS classification. Moreover, age and educational attainment have an independent impact on sleep quality. Unexpectedly, the VAS score for pain was not independently associated with the seriousness of sleep quality, which may be related to preemptive and multimodal analgesia. Further studies are required to clarify this ambiguity.
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http://dx.doi.org/10.1186/s13018-021-02487-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164244PMC
May 2021

Ultrafast Potassium Storage in F-Induced Ultra-High Edge-Defective Carbon Nanosheets.

ACS Nano 2021 Jun 26;15(6):10217-10227. Epub 2021 May 26.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Materials Science and Engineering, CAS Key Laboratory of Materials for Energy Conversion, University of Science and Technology of China, Hefei, Anhui 230026, China.

Carbonaceous materials have been considered as promising anodes for potassium-ion batteries (PIBs) because of their high electronic conductivity, eco-friendliness, and structural stability. However, the small interlayer spacing and serious volume expansion caused by the repeated insertion/extraction of large K-ions restrict their potassium-ion storage performance. Herein, F and N codoped carbon nanosheets (FNCS) with rich-edge defects are designed to resolve these problems. The F doping is in favor of the formation of more edge defects in the carbon layer, offering strong K adsorption capability and promoting the K storage. The ultrathin carbon nanosheets can provide a large contact area for the electrochemical reactions and shorten the transportation pathways for both K-ions and electrons. Consequently, the FNCS anode shows a high reversible capacity (610 mAh g at 0.1 A g) and ultrastable cyclability over 4000 cycles at 5 A g. Moreover, K-ion full cells (FNCS|KFeFe(CN)) display excellent cycling stability (128 mAh g at 1 A g after 500 cycles) and rate capability (93 mAh g at 20 A g). This design strategy can be extended to design other electrode materials for high-performance energy storage, such as magnesium-ion batteries, supercapacitors, and electrocatalysis.
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http://dx.doi.org/10.1021/acsnano.1c02275DOI Listing
June 2021

Modeling indoor-level non-pharmaceutical interventions during the COVID-19 pandemic: A pedestrian dynamics-based microscopic simulation approach.

Transp Policy (Oxf) 2021 Aug 16;109:12-23. Epub 2021 May 16.

Citadel, Chicago, IL, United States.

Mathematical modeling of epidemic spreading has been widely adopted to estimate the threats of epidemic diseases (i.e., the COVID-19 pandemic) as well as to evaluate epidemic control interventions. The indoor place is considered to be a significant epidemic spreading risk origin, but existing widely-used epidemic spreading models are usually limited for indoor places since the dynamic physical distance changes between people are ignored, and the empirical features of the essential and non-essential travel are not differentiated. In this paper, we introduce a pedestrian-based epidemic spreading model that is capable of modeling indoor transmission risks of diseases during people's social activities. Taking advantage of the before-and-after mobility data from the University of Maryland COVID-19 Impact Analysis Platform, it's found that people tend to spend more time in grocery stores once their travel frequencies are restricted to a low level. In other words, an increase in dwell time could balance the decrease in travel frequencies and satisfy people's demands. Based on the pedestrian-based model and the empirical evidence, combined non-pharmaceutical interventions from different operational levels are evaluated. Numerical simulations show that restrictions on people's travel frequency and open hours of indoor places may not be universally effective in reducing average infection risks for each pedestrian who visit the place. Entry limitations can be a widely effective alternative, whereas the decision-maker needs to balance the decrease in risky contacts and the increase in queue length outside the place that may impede people from fulfilling their travel needs. The results show that a good coordination among the decision-makers can contribute to the improvement of the performance of combined non-pharmaceutical interventions, and it also benefits the short-term and long-term interventions in the future.
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http://dx.doi.org/10.1016/j.tranpol.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124090PMC
August 2021

"Metal elements and pesticides as risk factors for Parkinson's disease - A review".

Toxicol Rep 2021 10;8:607-616. Epub 2021 Mar 10.

School of Life Sciences, Lanzhou University, China.

Essential metals including iron (Fe) and manganese (Mn) with known physiological functions in human body play an important role in cell homeostasis. Excessive exposure to these essential as well as non-essential metals including mercury (Hg) and Aluminum (Al) may contribute to pathological conditions, including PD. Each metal could be toxic through specific pathways. Epidemiological evidences from occupational and ecological studies besides various in vivo and in vitro studies have revealed the possible pathogenic role and neurotoxicity of different metals. Pesticides are substances that aim to mitigate the harm done by pests to plants and crops, and are extensively used to boost agricultural production. This review provides an outline of our current knowledge on the possible association between metals and PD. We have discussed the potential association between these two, furthermore the chemical properties, biological and toxicological aspects as well as possible mechanisms of Fe, Mn, Cu, Zn, Al, Ca, Pb, Hg and Zn in PD pathogenesis. In addition, we review recent evidence on deregulated microRNAs upon pesticide exposure and possible role of deregulated miRNA and pesticides to PD pathogenesis.
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http://dx.doi.org/10.1016/j.toxrep.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010213PMC
March 2021

SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance.

Cell Death Dis 2021 04 1;12(4):341. Epub 2021 Apr 1.

Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.

The JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.
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http://dx.doi.org/10.1038/s41419-021-03635-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016909PMC
April 2021

Conservative versus liberal oxygen therapy for acutely ill medical patients: A systematic review and meta-analysis.

Int J Nurs Stud 2021 Jun 9;118:103924. Epub 2021 Mar 9.

West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan 610041, China. Electronic address:

Background: The role of conservative versus liberal oxygen therapy for acutely ill patients remains controversial.

Objective: To systematically review the available evidence regarding the efficacy and safety of conservative oxygen therapy compared with liberal oxygen therapy for acutely ill patients.

Methods: A systematic search of Medline, Embase, and the Cochrane Central Register was conducted from their inception until April 5, 2020. Randomized clinical trials evaluating a high-target (liberal) or a low-target (conservative) oxygenation strategy in adults with an acutely ill condition were eligible for inclusion. A meta-analysis using random-effects models was conducted to calculate the risk ratio with corresponding 95% confidence intervals. Heterogeneity and publication bias were evaluated.

Results: The analyses included 33 randomized clinical trials with a total of 17,780 participants. Compared with conservative oxygen therapy, liberal oxygen therapy was not associated with increased mortality at 30 days (risk ratio 1.09, 95% confidence intervals 0.98-1.22; I=0%), at 90 days (risk ratio 1.00, 95% confidence intervals 0.88-1.13, I=37%), or at the longest follow-up (risk ratio 1.04, 95% confidence intervals 0.96-1.12, I=0%). Good functional outcome was similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses.

Conclusions: Compared with liberal oxygen therapy, conservative oxygen therapy was not associated with decreased mortality. Tweetable abstract: Compared with liberal oxygen therapy, conservative oxygen therapy was not associated with decreased mortality.
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http://dx.doi.org/10.1016/j.ijnurstu.2021.103924DOI Listing
June 2021

17-Hydroxybrevianamide N and Its N1-Methyl Derivative, Quinazolinones from a Soft-Coral-Derived sp. Fungus: 13 Enantiomers as the True Natural Products.

J Nat Prod 2021 04 25;84(4):1353-1358. Epub 2021 Mar 25.

Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

Under the guidance of MS/MS-based molecular networking and HPLC-UV, two new alkaloid racemates, (±)-17-hydroxybrevianamide N () and (±)-N1-methyl-17-hydroxybrevianamide N (), featuring a rare -hydroxyphenylalanine residue and an imide subunit, were isolated from a soft-coral-derived sp. fungus. The true natural products (+)- and (+)- were further monitored and obtained from the freshly prepared EtOAc extracts, while (-)- and (-)- are artifacts generated during extraction and purification processes. Simultaneously, the structures including absolute configurations of (+)-13-, (-)-13-, (+)-13-, and (-)-13- were elucidated on the basis of comprehensive spectroscopic analysis, ECD calculations, and X-ray diffraction data. Interestingly, basic solution promotes the racemization of (+)- and (-)-, whereas acidic solution suppresses the transformation. The current research was concerned with the true natural products and their artifacts, providing critical insight into the isolation and identification of natural products.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00098DOI Listing
April 2021

Cross-platform comparison of immune-related gene expression to assess intratumor immune responses following cancer immunotherapy.

J Immunol Methods 2021 Jul 19;494:113041. Epub 2021 Mar 19.

Department of Medicine, University of California San Francisco, San Francisco, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Neoadjuvant immunotherapy can induce immune responses within the tumor microenvironment. Gene expression can be used to assess responses with limited amounts of conventionally-fixed patient-derived samples. We aim to assess the cross-platform concordance of immune-related gene expression data. We performed comparisons across three panels in two platforms: Nanostring nCounter® PanCancer Immune Profiling Panel (nS), HTG EdgeSeq Oncology Biomarker Panel (HTG OBP) and Precision Immuno-Oncology Panel (HTG PIP). All tissue samples of 14 neoadjuvant GM-CSF treated, 14 neoadjuvant Provenge treated, and 12 untreated prostate cancer patients were radical prostatectomy (RP) tissues, while 6 prostatitis patients and 6 non-prostatitis subjects were biopsies. For all 52 patients, more than 90% of the common genes were significantly correlated (p < 0.05) and more than 76% of the common genes were highly correlated (r > 0.5) between any two panels. Co-inertia analysis also demonstrated high overall dataset structure similarity (correlation>0.84). Although both dimensionality reduction visualization analysis and unsupervised hierarchical cluster analysis for highly correlated common genes (r > 0.9) suggested a high-level of consistency across the panels, there were subsets of genes that were differentially expressed across the panels. In addition, while the effect size of the differential testing for neoadjuvant treated vs. untreated localized prostate cancer patients across the panels were significantly correlated, some genes were only differentially expressed in the HTG panels. Finally, the HTG PIP panel had the best classification performance among the 3 panels. These differences detected may be a result of the different panels or platforms due to their technical setting and focus. Thus, researchers should be aware of those potential differences when deciding which platform and panel to use.
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http://dx.doi.org/10.1016/j.jim.2021.113041DOI Listing
July 2021

Iron Coordination Polymer, Fe(oxalate)(HO) Nanorods Grown on Nickel Foam via One-Step Electrodeposition as an Efficient Electrocatalyst for Oxygen Evolution Reaction.

Inorg Chem 2021 Apr 22;60(7):5140-5152. Epub 2021 Mar 22.

Department of Applied Chemistry, College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, P. R. China.

Iron coordination polymer, Fe(ox)(HO) (Hox = oxalic acid) nanorods were grown on a nickel foam (NF) collector via a one-step electrodeposition method, which can be directly used as a freestanding and binder-free electrode for efficient oxygen evolution reaction (OER) electrocatalysis. The optimum sample, Fe(ox)(HO)/NF-(-1.4)-15, was obtained at an electrodeposition potential of -1.4 V vs Ag/AgCl for 15 min, which can deliver OER current densities of 40 and 100 mA cm at overpotentials of 270 and 340 mV, respectively. The sample also exhibits good long-term OER activity during 80 h electrolysis at 20 mA cm, which is superior to those of previously reported metal-organic framework (MOF) catalysts. Furthermore, the formation mechanism of the Fe(ox)(HO) nanorods is primarily investigated and the effect of the species of metal ions in MOF on the morphology and OER behavior is also explored. In addition, density functional theory (DFT) calculations reveal that the rate-limiting steps on Fe(ox)(HO) and Ni(ox)(HO) are the formation of Fe*-OOH and Ni*-OH intermediates with maximum Δ values of 1.628 and 1.710 eV, respectively, which is attributed to the different electronic configurations of Ni and Fe, thus giving rise to different d-band centers and different affinities for adsorbates.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00170DOI Listing
April 2021

The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter.

Oncogene 2021 Mar 2;40(12):2309-2322. Epub 2021 Mar 2.

Interdisciplinary Center for Clinical Research (IZKF), Friedrich-Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany.

Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs endogenous levels and activity for in vitro and in vivo applications could lead to a better understanding of their biological role in physiology and disease.
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http://dx.doi.org/10.1038/s41388-021-01708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994202PMC
March 2021

Effect of patient-controlled intravenous analgesia combined with flurbiprofen axetil and dezocine on postoperative analgesia for lobectomy (EPIC-FAD): a trial protocol.

Trials 2021 Mar 1;22(1):175. Epub 2021 Mar 1.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.

Background: The optimal analgesic strategy for surgical pain after lobectomy remains undefined. To compare the combination of flurbiprofen axetil and dezocine with flurbiprofen axetil alone and dezocine alone, in post-lobectomy patients.

Methods: A single-center, parallel-design double-blind superiority trial, with 5 groups (1:1:1:1:1 ratio) with different combinations of flurbiprofen and dezocine. Patients scheduled for lobectomy will be recruited. The primary outcome is total sufentanil use in patient-controlled intravenous analgesia within the first 24 postoperative hours. Secondary outcomes include pain numeric rating scales at 6th, 12th, 24th, 48th, and 72th postoperative hours, and on the 1st, 3rd, and 6th postoperative months at rest and during coughing, adverse effects from experimental drug treatment, sufentanil use at other time points, analgesia cost, time to chest tube removal, length of hospital stay, time to pass first flatus, and serum level of cytokines. Doctors, patients, and nurses are blinded, and only the manager is unblinded. Analysis is intention-to-treat. Statistical analysis is pre-specified. Statistical comparison of the treatment groups includes one-way analysis of variance followed by Tukey's post hoc test.

Discussion: Trial did not begin to recruit. Participant recruitment start date is planned to be June 1, 2020. Approximate recruitment end date is May 31, 2021. If successful, the trial may shed light on the use of certain analgesic combinations in post-lobectomy pain control.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800018563 . Registered on September 25, 2018.
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http://dx.doi.org/10.1186/s13063-021-05108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923454PMC
March 2021

Role of circular RNA expression in the pathological progression after spinal cord injury.

Neural Regen Res 2021 Oct;16(10):2048-2055

Department of Orthopedics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan Province, China.

Differential expression of non-coding RNA after traumatic spinal cord injury (TSCI) is closely related to the pathophysiological process. The purposes of this study were to systematically profile and characterize expression of circular RNA (circRNA) in the lesion epicenter of spinal tissues after TSCI, and predict the structure and potential function of the regulatory circRNA/miRNA network. Forty-eight C57BL/6 mice were randomly and equally assigned to two groups: one subjected to TSCI at T8-10 with an Allen's drop impactor, and a second subjected to laminectomy without TSCI. Spinal cord samples were stained with hematoxylin and eosin, sequenced, and validated. RNA-Seq, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and network analyses (Targetscan and miRanda) were used to predict and annotate the circRNA/miRNA/mRNA network. Luciferase reporter, quantitative reverse transcription polymerase chain reaction, and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI. Hematoxylin-eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI. Differentially expressed circRNA and miRNA profiles were obtained after TSCI; differentially expressed circRNAs, which were abundant in the cytoplasm, were involved in positive regulation of transcription and protein phosphorylation. miR-135b-5p was the most significantly downregulated miRNA after TSCI; circRNAAbca1 and KLF4 were predicted to be its target circRNA and mRNA, respectively. Subsequently, the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed, and its targeted binding was verified. After inhibiting circAbca1, GAP43 expression was upregulated. Differential expression of circRNAs might play an important role after TSCI. circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis. The identified circRNA/miRNA/mRNA network could provide the basis for understanding pathophysiological mechanisms underlying TSCI, as well as guide the formulation of related therapeutic strategies. All animal protocols were approved by the Research Ethics Committee of West China Hospital of China (approval No. 2017128) on May 16, 2017.
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http://dx.doi.org/10.4103/1673-5374.308100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343338PMC
October 2021

Subtype-GAN: a deep learning approach for integrative cancer subtyping of multi-omics data.

Bioinformatics 2021 Feb 18. Epub 2021 Feb 18.

Department of Computer Science and Engineering, East China University of Science and Technology, Shanghai 200237, PR China.

Motivation: The discovery of cancer subtyping can help explore cancer pathogenesis, determine clinical actionability in treatment, and improve patients' survival rates. However, due to the diversity and complexity of multi-omics data, it is still challenging to develop integrated clustering algorithms for tumor molecular subtyping.

Results: We propose Subtype-GAN, a deep adversarial learning approach based on the multiple-input multiple-output neural network to model the complex omics data accurately. With the latent variables extracted from the neural network, Subtype-GAN uses consensus clustering and the Gaussian Mixture model to identify tumor samples' molecular subtypes. Compared with other state-of-the-art subtyping approaches, Subtype-GAN achieved outstanding performance on the benchmark data sets consisting of ∼4,000 TCGA tumors from 10 types of cancer. We found that on the comparison data set, the clustering scheme of Subtype-GAN is not always similar to that of the deep learning method AE but is identical to that of NEMO, MCCA, VAE, and other excellent approaches. Finally, we applied Subtype-GAN to the BRCA data set and automatically obtained the number of subtypes and the subtype labels of 1031 BRCA tumors. Through the detailed analysis, we found that the identified subtypes are clinically meaningful and show distinct patterns in the feature space, demonstrating the practicality of Subtype-GAN.

Availability: The source codes, the clustering results of Subtype-GAN across the benchmark data sets are available at https://github.com/haiyang1986/Subtype-GAN.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab109DOI Listing
February 2021

Effects of Melatonin on Dairy Herd Improvement (DHI) of Holstein Cow with High SCS.

Molecules 2021 Feb 5;26(4). Epub 2021 Feb 5.

National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Mastitis is a common disease in cows breeding. The milk quality will be significantly reduced with increased milk somatic cells, which often occurs in cows with mastitis. In this study, the influence of seasonal changes, age and lactation stages in the Dairy Herd Improvement (DHI) of cows was investigated. Then, the Dairy Herd Improvement (DHI) of cows with high somatic cell score (SCS) after melatonin treatment was systemically investigated. The results showed that melatonin significantly suppressed the milk somatic cell score under all of the tested conditions. The melatonin treatment also improved the milk nutritional value by reducing its fat but increasing its lactose and protein contents. The application of melatonin significantly improved the DHI. The beneficial effects of melatonin on DHI are likely attributed to the antioxidant and anti-inflammatory activities of melatonin.
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http://dx.doi.org/10.3390/molecules26040834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915447PMC
February 2021

Effects of Vitamin D Supplementation on Prevention of Type 2 Diabetes in Patients With Prediabetes: A Systematic Review and Meta-analysis.

Diabetes Care 2020 07;43(7):1650-1658

West China Hospital, Sichuan University, Chengdu, Sichuan, China

Background: While observational studies have shown an association between vitamin D insufficiency and diabetes, it is unclear whether intervention with vitamin D supplements can lower the risk of type 2 diabetes mellitus (T2DM).

Purpose: To assess whether vitamin D supplementation reduces the risk of T2DM in people with prediabetes.

Data Sources: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 5 July 2019.

Study Selection: We included randomized controlled trials assessing vitamin D supplementation versus placebo in relation to new-onset T2DM in people with prediabetes.

Data Extraction: We screened studies and extracted data from published trials independently.

Data Synthesis: We identified eight eligible trials with a total of 4,896 subjects. Vitamin D supplementation significantly reduced the risk of T2DM (risk ratio [RR] 0.89 [95% CI 0.80-0.99]; = 0%). Benefit was found in nonobese subjects (RR 0.73 [95% CI 0.57-0.92]) but not in obese subjects (RR 0.95 [95% CI 0.84-1.08]) ( = 0.048). The reversion of prediabetes to normoglycemia occurred in 116 of 548 (21.2%) participants in the vitamin D group and 75 of 532 (14.1%) in the control group. Vitamin D supplementation increased reversion rate of prediabetes to normoglycemia (RR 1.48 [95% CI 1.14-1.92]; = 0%.) LIMITATIONS: Definitions of prediabetes and new-onset diabetes in eligible studies were different, and long-term data on outcomes of T2DM prevention were lacking.

Conclusions: In persons with prediabetes, vitamin D supplementation reduces the risk of T2DM and increases the reversion rate of prediabetes to normoglycemia. The benefit of the prevention of T2DM could be limited to nonobese subjects. Individual participant data meta-analyses are needed to confirm these findings.
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http://dx.doi.org/10.2337/dc19-1708DOI Listing
July 2020
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