Publications by authors named "Yanming Li"

148 Publications

Rates of bone reabsorption and union in mandibular reconstruction using the osteocutaneous radial forearm free flap.

Head Neck 2021 Nov 24. Epub 2021 Nov 24.

Department of Otolaryngology - Head and Neck Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA.

Background: Historical concerns over bone resorption and malunion of the osteocutaneous radial forearm free flap (OCRFFF) limited its widespread adoption for head and neck reconstruction, despite lack of outcomes data evaluating this notion.

Methods: A retrospective cohort study was performed including patients 18 years or older who underwent reconstruction of the mandible using an OCRFFF. Linear modeling and logistic regression were used to evaluate the change in bone volume and union over time.

Results: One hundred and twenty-one patients were included in the study. A mixed effects linear model incorporating age, sex, treatment type, and number of bone segments did not demonstrate a significant loss of bone volume over time. A logistic regression model identified lack of adjuvant treatment and time to be significantly associated with complete union.

Conclusion: This study supports that the OCRFFF is a stable form of osseus reconstruction for defects of the head and neck.
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http://dx.doi.org/10.1002/hed.26939DOI Listing
November 2021

Negative anti-neutrophil cytoplasmic antibodies and eosinophilic granulomatosis with polyangiitis accompanied by cough variant asthma: a case report.

Ann Palliat Med 2021 10;10(10):11209-11215

Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a rare chronic necrotizing eosinophilic granulomatous inflammatory disease characterized by eosinophil-rich granulomatous inflammation and small- to medium-size vessel vasculitis associated with bronchial asthma and eosinophilia, which is positive for anti-neutrophil cytoplasmic antibody (ANCA) in approximately 50-70% of cases. We report a case of a 23-year-old woman was admitted to our hospital because of a of small vesicles on both lower limbs and a 4-month history of small scattered skin rash with pruritus V6 on both lower limbs four-month history of scattered skin rash with pruritus. Laboratory data from peripheral blood revealed leukocytosis, eosinophilia, thrombocytosis, hyperfibrinolysis, and mild renal injury. Her ANCA was negative, and the skin pathological examination showed granuloma lesions with eosinophils, while elevated eosinophils were also found in the bone marrow. EGPA was diagnosed. On the other hand, the patient had 2-year-long rhinosinusitis, 9-month-long nephrotic syndrome, and 1-month-long dry cough, which might be a type of asthma. With steroid therapy followed by systemic immunomodulatory therapy, the patient's symptoms were relieved. Our case report and literature review highlight the importance of recognizing cough variant asthma as an initial presenting symptom of EGPA, providing an opportunity for early diagnosis and treatment to reduce the risk of further disease progression and morbidity.
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http://dx.doi.org/10.21037/apm-21-2236DOI Listing
October 2021

Molecular and Cellular Dynamics of Aortic Aneurysms Revealed by Single-Cell Transcriptomics.

Arterioscler Thromb Vasc Biol 2021 11 7;41(11):2671-2680. Epub 2021 Oct 7.

Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX.

The aorta is highly heterogeneous, containing many different types of cells that perform sophisticated functions to maintain aortic homeostasis. Recently, single-cell RNA sequencing studies have provided substantial new insight into the heterogeneity of vascular cell types, the comprehensive molecular features of each cell type, and the phenotypic interrelationship between these cell populations. This new information has significantly improved our understanding of aortic biology and aneurysms at the molecular and cellular level. Here, we summarize these findings, with a focus on what single-cell RNA sequencing analysis has revealed about cellular heterogeneity, cellular transitions, communications among cell populations, and critical transcription factors in the vascular wall. We also review the information learned from single-cell RNA sequencing that has contributed to our understanding of the pathogenesis of vascular disease, such as the identification of cell types in which aneurysm-related genes and genetic variants function. Finally, we discuss the challenges and future directions of single-cell RNA sequencing applications in studies of aortic biology and diseases.
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http://dx.doi.org/10.1161/ATVBAHA.121.315852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556647PMC
November 2021

Programmed cell death in aortic aneurysm and dissection: A potential therapeutic target.

J Mol Cell Cardiol 2021 Sep 28;163:67-80. Epub 2021 Sep 28.

Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Cardiovascular Surgery, Texas Heart Institute, 6770 Bertner Ave., Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address:

Rupture of aortic aneurysm and dissection (AAD) remains a leading cause of death. Progressive smooth muscle cell (SMC) loss is a crucial feature of AAD that contributes to aortic dysfunction and degeneration, leading to aortic aneurysm, dissection, and, ultimately, rupture. Understanding the molecular mechanisms of SMC loss and identifying pathways that promote SMC death in AAD are critical for developing an effective pharmacologic therapy to prevent aortic destruction and disease progression. Cell death is controlled by programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis. Although these pathways share common stimuli and triggers, each type of programmed cell death has unique features and activation pathways. A growing body of evidence supports a critical role for programmed cell death in the pathogenesis of AAD, and inhibitors of various types of programmed cell death represent a promising therapeutic strategy. This review discusses the different types of programmed cell death pathways and their features, induction, contributions to AAD development, and therapeutic potential. We also highlight the clinical significance of programmed cell death for further studies.
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http://dx.doi.org/10.1016/j.yjmcc.2021.09.010DOI Listing
September 2021

A Structured Brain-wide and Genome-wide Association Study Using ADNI PET Images.

Can J Stat 2021 Mar 20;49(1):182-202. Epub 2021 Feb 20.

Department of Statistics, University of Michigan Ann Arbor, MI 48109.

A multi-stage variable selection method is introduced for detecting association signals in structured brain-wide and genome-wide association studies (brain-GWAS). Compared to conventional single-voxel-to-single-SNP approaches, our approach is more efficient and powerful in selecting the important signals by integrating anatomic and gene grouping structures in the brain and the genome, respectively. It avoids large number of multiple comparisons while effectively controls the false discoveries. Validity of the proposed approach is demonstrated by both theoretical investigation and numerical simulations. We apply the proposed method to a brain-GWAS using ADNI PET imaging and genomic data. We confirm previously reported association signals and also find several novel SNPs and genes that either are associated with brain glucose metabolism or have their association significantly modified by Alzheimer's disease status.
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http://dx.doi.org/10.1002/cjs.11605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460073PMC
March 2021

New Technologies With Increased Precision Improve Understanding of Endothelial Cell Heterogeneity in Cardiovascular Health and Disease.

Front Cell Dev Biol 2021 27;9:679995. Epub 2021 Aug 27.

Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States.

Endothelial cells (ECs) are vital for blood vessel integrity and have roles in maintaining normal vascular function, healing after injury, and vascular dysfunction. Extensive phenotypic heterogeneity has been observed among ECs of different types of blood vessels in the normal and diseased vascular wall. Although ECs with different phenotypes can share common functions, each has unique features that may dictate a fine-tuned role in vascular health and disease. Recent studies performed with single-cell technology have generated powerful information that has significantly improved our understanding of EC biology. Here, we summarize a variety of EC types, states, and phenotypes recently identified by using new, increasingly precise techniques in transcriptome analysis.
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http://dx.doi.org/10.3389/fcell.2021.679995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430032PMC
August 2021

The order of degeneration of lumbar intervertebral disc and lumbar facet joint and its correlation with age.

Minerva Med 2021 Sep 3. Epub 2021 Sep 3.

Department of Orthopedics, Affiliated Hospital of Jining Medical University, Jining, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07610-2DOI Listing
September 2021

Clinical characteristics and risk factors for death in patients with bloodstream infection in Intensive Care Unit.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Jul;46(7):719-724

Medical College of Hunan Normal University, Changsha 410006, China.

Objectives: To analyze the distribution of pathogens and risk factors of mortality in bloodstream infection patients in Intensive Care Unit (ICU).

Methods: The clinical data, infection relevant indexes, and prognosis of patients with bloodstream infection in ICU of Xiangya Hospital of Central South University from January 2016 to December 2020 were retrospectively collected. The distribution of pathogenic bacteria and clinical characteristics of patients with bloodstream infection were analyzed. The patients were assigned into a death group and a survival group according to their survival status, and single factor analysis and logistic regression analysis were used to analyze risk factors for death.

Results: A total of 80 patients with bloodstream infection were enrolled, with the highest infection rate (36.3%) of . According to the drug sensitivity, all kinds of s were wide type and relatively sensitive to amphotericin B. was highly sensitive to fluconazole, itraconazole, and voriconazole (≥96.6%), while non- were more resistant to fluconazole, itraconazole, and voriconazole. The overall mortality rate was 36.3%. Univariate analysis showed that the risk factors for the death of patients with bloodstream infection were acute physiology and chronic health evaluation II (APACHE II) score≥20, diabetes mellitus, and mechanical ventilation. Logistic regression analysis showed that the APACHE II score≥20 was an independent risk factor for the death of patients with bloodstream infection (OR=0.220, 95% CI 0.078 to 0.619, =0.004).

Conclusions: The most common strain of bloodstream infection in ICU patients is . The APACHE II score≥20 is an independent risk factor for the death of patients with bloodstream infection.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.201012DOI Listing
July 2021

Mapping Human Pluripotent Stem Cell-derived Erythroid Differentiation by Single-cell Transcriptome Analysis.

Genomics Proteomics Bioinformatics 2021 Jul 17. Epub 2021 Jul 17.

CAS Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences/China National Center of Bioinformation, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100190, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Key Laboratory of Genome and Precision Medicine Technologies, Beijing, 100101, China. Electronic address:

There is an imbalance between the supply and demand of functional red blood cells (RBCs) in clinical applications. This imbalance can be addressed by regenerating RBCs using several in vitro methods. Induced pluripotent stem cells (iPSCs) can handle the low supply of cord blood and the ethical issues in embryonic stem cell research and provide a promising strategy to eliminate immune rejection. However, no complete single-cell level differentiation pathway exists for the iPSC-derived RBC differentiation system. In this study, we used iPSC line BC1 to establish a RBCs regeneration system. The 10× genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectories on day 14 of the regeneration system. We observed that iPSCs differentiation was not synchronized during embryoid body (EB) culture. The cells (day 14) mainly consisted of mesodermal and various blood cells, similar to the yolk sac hematopoiesis. We identified six cell classifications and characterized the regulatory transcription factors (TFs) networks and cell-cell contacts underlying the system. iPSCs undergo two transformations during the differentiation trajectory, accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes. We identified different stages of erythroid cells, such as burst-forming unit erythroid (BFU-E) and orthochromatic erythroblasts (ortho-E), and found that the regulation of TFs (e.g., TFDP1 and FOXO3) is erythroid-stage specific. Immune erythroid cells were identified in our system. This study provides systematic theoretical guidance for optimizing the iPSCs-derived RBCs differentiation system, and this system is a useful model for simulating in vivo hematopoietic development and differentiation.
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http://dx.doi.org/10.1016/j.gpb.2021.03.009DOI Listing
July 2021

Ultrasound-assisted CF-filled PLGA nanobubbles for enhanced FGF21 delivery and improved prophylactic treatment of diabetic cardiomyopathy.

Acta Biomater 2021 08 12;130:395-408. Epub 2021 Jun 12.

Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China.; Department of Ultrasound in Medicine, Shanghai Eighth People's Hospital, 8 Caobao Road, Shanghai 200235, PR China. Electronic address:

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment. Fibroblast growth factor 21 (FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of FGF21 in DCM, an effective drug delivery system is urgently required. In this study, perfluoropropane (CF) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles (CPPNBs) were synthesized via double-emulsion evaporation and FGF21 was efficiently absorbed ([email protected]) via the electrostatic incorporation effect. [email protected] could effectively deliver FGF21 to the myocardial tissue through the cavitation effect under low-frequency ultrasound (LFUS). The as-prepared [email protected] could efficiently load FGF21 after doping with the cationic polymer PEI, and displayed uniform dispersion and favorable biosafety. After filling with CF, [email protected] could be used for distribution monitoring through ultrasound imaging. Moreover, [email protected] significantly downregulated the expression of ANP, CTGF, and caspase-3 mRNA via the action of LFUS owing to increased FGF21 release, therefore exhibiting enhanced inhibition of myocardial hypertrophy, apoptosis, and interstitial fibrosis in DCM mice. In conclusion, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM. STATEMENT OF SIGNIFICANCE: Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks effective clinical treatments. Fibroblast growth factor 21 (FGF21) can protect cardiomyocytes from diabetic damage, but insufficient cardiac drug delivery limits the application of FGF21 in DCM. In this study, perfluoropropane (C3F8) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles loaded with FGF21 ([email protected]) were developed for the prophylactic treatment of DCM. CPPNBs[email protected] could effectively deliver the FGF21 to the myocardial tissue through the cavitation effect of low-frequency ultrasound (LFUS). Our results indicated that [email protected] combined with LFUS could significantly down-regulate the expressions of ANP, CTGF, and caspase-3 mRNA, and as a result, it prevented the myocardial hypertrophy, apoptosis, and interstitial fibrosis of DCM mice. Overall, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM.
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http://dx.doi.org/10.1016/j.actbio.2021.06.015DOI Listing
August 2021

SurvBoost: An R Package for High-Dimensional Variable Selection in the Stratified Proportional Hazards Model via Gradient Boosting.

R J 2020 Jun;12(1):105-117

Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109.

High-dimensional variable selection in the proportional hazards (PH) model has many successful applications in different areas. In practice, data may involve confounding variables that do not satisfy the PH assumption, in which case the stratified proportional hazards (SPH) model can be adopted to control the confounding effects by stratification without directly modeling the confounding effects. However, there is a lack of computationally efficient statistical software for high-dimensional variable selection in the SPH model. In this work an R package, , is developed to implement the gradient boosting algorithm for fitting the SPH model with high-dimensional covariate variables. Simulation studies demonstrate that in many scenarios can achieve better selection accuracy and reduce computational time substantially compared to the existing R package that implements boosting algorithms without stratification. The proposed R package is also illustrated by an analysis of gene expression data with survival outcome in The Cancer Genome Atlas study. In addition, a detailed hands-on tutorial for is provided.
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http://dx.doi.org/10.32614/rj-2020-018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174798PMC
June 2020

Clinical features in pulmonary tuberculosis patients combined with diabetes mellitus in China: An observational study.

Clin Respir J 2021 Sep 26;15(9):1012-1018. Epub 2021 Jul 26.

Department of Pulmonary and Critical Care Medicine, Beijing Hospital, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: Consideration of the huge burden both of tuberculosis (TB) and diabetes mellitus (DM) in China as a major public health issue, research focused on the relationship between DM and TB was needed.

Methods: An observational study was conducted (2015-2018) in regional representative TB and lung disease hospitals in China. All the adult patients newly diagnosed of pulmonary TB were consecutively recruited in this study.

Results: A total of 1417 patients newly diagnosed pulmonary TB was recruited in this research, 312 (22.02%) of them had the history of type 2 DM. Majority of patients were with fatigue, loss of weight and mild anaemia in TB-DM group compared with TB-NDM group (58.3% vs 47.5%, p = .001; 8.21 ± 6.2 vs 5.74 ± 4.0 kg, p < .001, 88.9% vs 77.6% p = .021). TB-DM patients were with higher the proportion of TB severity score ≥3, compared with TB-NDM patients, but the distributions of drug susceptibility testing (DST) analysis were not significantly different between the two groups of patients. Remarkably, the sign of central shadow of pulmonary lobe distribution and cavity in TB-DM group presented significantly higher rate than it in TB-NDM group. Multivariable logistic regression showed that high uric acid level was an independent risk factor for thick wall cavity in TB-DM patients (OR 2.81, 95% CI 1.24-6.40), haemoptysis (OR 2.43, 95% CI 1.10-5.38) and chest pain (OR 5.22, 95% CI 1.38-19.70) were significantly associated with thick wall cavity.

Conclusions: The clinical features of TB-DM patients are associated with cavities in CT scan, rather than DST results. It can help us recognition confounding variables, also may influence the treatment strategy and outcomes in TB-DM patients.
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http://dx.doi.org/10.1111/crj.13405DOI Listing
September 2021

Pretreatment by composting increased the utilization proportion of pig manure biogas digestate and improved the seedling substrate quality.

Waste Manag 2021 Jun 21;129:47-53. Epub 2021 May 21.

College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China.

Anaerobic digestion of organic residues has the potential to significantly contribute to a shift from fossil to renewable energy, while the remaining biogas digestate need to be treated or used for a second time. In this study, the pig manure biogas digestate (PMBD) was evaluated as a potential part of seedling substrates and composting was considered a pretreating method to improve its characters. Composting was carried out firstly in a forced aeration composting system (100 L), in which perlite and sawdust were used as additives in different proportions separately or together. Based on the comparison of the physicochemical characters of different seedling substrates formulas mixed with PMBD or pig manure biogas digestate pretreated by composting (CPMBD), selected seedling substrates were analyzed by bioassay experiment. The results showed that pretreatment by composting and the additives (perlite and sawdust) used in composting decreased the pH value of PMBD and make it suitable for seedling substrates, especially composted with perlite and sawdust. Both PMBD and CPMBD with low proportion in the substrates improved plant growth of lettuce and tomato, while CPMBD was better than PMBD. However, when the proportions of PMBD was increased more than 20% and CPMBD was increased more than 40%, plant growth inhibition was observed. Tomato was more sensitive than lettuce to the physicochemical characters of the substrate. In summary, PMBD pretreated by composting not only increases the uses of digestate, but also enhances plant growth and hence yield.
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http://dx.doi.org/10.1016/j.wasman.2021.05.010DOI Listing
June 2021

4-phenylbutyrate exerts stage-specific effects on cardiac differentiation via HDAC inhibition.

PLoS One 2021 21;16(4):e0250267. Epub 2021 Apr 21.

School of Medicine, Hunan Normal University, Changsha, Hunan, China.

4-phenylbutyrate (4-PBA), a terminal aromatic substituted fatty acid, is used widely to specifically attenuate endoplasmic reticulum (ER) stress and inhibit histone deacetylases (HDACs). In this study, we investigated the effect of 4-PBA on cardiac differentiation of mouse embryonic stem (ES) cells. Herein, we found that 4-PBA regulated cardiac differentiation in a stage-specific manner just like trichostatin A (TSA), a well-known HDAC inhibitor. 4-PBA and TSA favored the early-stage differentiation, but inhibited the late-stage cardiac differentiation via acetylation. Mechanistic studies suggested that HDACs exhibited a temporal expression profiling during cardiomyogenesis. Hdac1 expression underwent a decrease at the early stage, while was upregulated at the late stage of cardiac induction. During the early stage of cardiac differentiation, acetylation favored the induction of Isl1 and Nkx2.5, two transcription factors of cardiac progenitors. During the late stage, histone acetylation induced by 4-PBA or TSA interrupted the gene silence of Oct4, a key determinant of self-renewal and pluripotency. Thereby, 4-PBA and TSA at the late stage hindered the exit from pluripotency, and attenuated the expression of cardiac-specific contractile proteins. Overexpression of HDAC1 and p300 exerted different effects at the distinct stages of cardiac induction. Collectively, our study shows that timely manipulation of HDACs exhibits distinct effects on cardiac differentiation. And the context-dependent effects of HDAC inhibitors depend on cell differentiation states marked by the temporal expression of pluripotency-associated genes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250267PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059837PMC
September 2021

Anaerobic digestion of agricultural wastes from liquid to solid state: Performance and environ-economic comparison.

Bioresour Technol 2021 Jul 30;332:125080. Epub 2021 Mar 30.

Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100093, China; Organic Recycling Institute (Suzhou) of China Agricultural University, Wuzhong District, 215128 Jiangsu Province, China. Electronic address:

Performance and environ-economic impacts were compared for anaerobic digestion (AD) of dairy manure and cucumber residues from liquid to solid state. Environ-economic evaluation of the overall AD process at different total solids (TS) was performed with the estimated treatment capacity of 9600 tons/year and service life of 20 years. Results showed that TS increase from 6% to 22% enhanced both cumulative and volumetric methane (CH) production. Further TS increase to 25%, however, reduced CH yield. Environ-economic assessment indicated that TS increase enhanced volumetric waste treatment capacity and thus AD environmental footprints. Environmental credits from digestate and biogas utilization could compensate the adverse environmental impacts of other processes in AD plants. Furthermore, biogas and nutrients in digestate determined AD net-present value. As a result, solid state AD was more profitable with higher CH yield and more nutrients in both biosolids and digested effluent of digestate than its liquid and hemi-solid counterparts.
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http://dx.doi.org/10.1016/j.biortech.2021.125080DOI Listing
July 2021

Clinical characteristics and outcome of influenza virus infection among adults hospitalized with severe COVID-19: a retrospective cohort study from Wuhan, China.

BMC Infect Dis 2021 Apr 12;21(1):341. Epub 2021 Apr 12.

Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, the Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus.

Methods: Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected.

Results: Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model.

Conclusions: Influenza virus IgM positive may be associated with decreasing in-hospital death.
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http://dx.doi.org/10.1186/s12879-021-05975-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040362PMC
April 2021

Bacterial dynamics and functions driven by bulking agents to mitigate gaseous emissions in kitchen waste composting.

Bioresour Technol 2021 Jul 29;332:125028. Epub 2021 Mar 29.

Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, PR China. Electronic address:

This study investigated the impacts of different bulking agents (i.e. garden waste, cornstalks, and spent mushroom substrates) on bacterial structure and functions for gaseous emissions during kitchen waste composting. High-throughput sequencing was integrated with functional Annotation of Prokaryotic Taxa (FAPROTAX) to decipher the bacterial structure and functions. Results show that adding cornstalks constructed a more complex and mutualistic bacterial network to enhance organic biodegradation. This scenario, however, aggravated the emission of ammonia and hydrogen sulphide with the enrichment of the genus Bacillus and Desulfitibacter at the thermophilic stage of composting to facilitate ammonification and sulphur-related respiration, respectively. By contrast, spent mushroom substrates facilitated the proliferation of the genus Pseudomonas to promote nitrate reduction at the cooling stage, leading to considerable emission of nitrous oxide. Compared to these two agents, garden waste contained less easily biodegradable substances to limit bacterial mutualism, thereby reducing gaseous emissions in composting.
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http://dx.doi.org/10.1016/j.biortech.2021.125028DOI Listing
July 2021

Systematic identification of risk factors and drug repurposing options for Alzheimer's disease.

Alzheimers Dement (N Y) 2021 3;7(1):e12148. Epub 2021 Mar 3.

Tulane Center for Biomedical Informatics and Genomics Deming Department of Medicine Tulane University School of Medicine New Orleans Louisiana USA.

Introduction: Several Mendelian randomization studies have been conducted that identified multiple risk factors for Alzheimer's disease (AD). However, they typically focus on a few pre-selected risk factors.

Methods: A two-sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1037 risk factors/medical conditions and 31 drugs with the risk of late-onset AD. To correct for multiple comparisons, the false discovery rate was set at  0.05.

Results: There was strong evidence of a causal association between glioma risk, reduced trunk fat-free mass, lower education levels, lower intelligence and a higher risk of AD. For 31 investigated treatments (such as antihypertensive drugs), we found limited evidence for their associations.

Discussion: MR found robust evidence of causal associations between glioma, trunk fat-free, and AD. Our study also confirms that higher educational attainment and higher intelligence are associated with a reduced risk of AD.
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http://dx.doi.org/10.1002/trc2.12148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927163PMC
March 2021

A gene-level methylome-wide association analysis identifies novel Alzheimer's disease genes.

Bioinformatics 2021 Feb 1. Epub 2021 Feb 1.

Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine.

Motivation: Transcriptome-wide association studies (TWAS) have successfully facilitated the discovery of novel genetic risk loci for many complex traits, including late-onset Alzheimer's disease (AD). However, most existing TWAS methods rely only on gene expression and ignore epigenetic modification (i.e., DNA methylation) and functional regulatory information (i.e., enhancer-promoter interactions), both of which contribute significantly to the genetic basis of AD.

Results: We develop a novel gene-level association testing method that integrates genetically regulated DNA methylation and enhancer-target gene pairs with genome-wide association study (GWAS) summary results. Through simulations, we show that our approach, referred to as the CMO (cross methylome omnibus) test, yielded well controlled type I error rates and achieved much higher statistical power than competing methods under a wide range of scenarios. Furthermore, compared with TWAS, CMO identified an average of 124% more associations when analyzing several brain imaging-related GWAS results. By analyzing to date the largest AD GWAS of 71,880 cases and 383,378 controls, CMO identified six novel loci for AD, which have been ignored by competing methods.

Availability: Software: https://github.com/ChongWuLab/CMO.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337007PMC
February 2021

Theoretical Studies and Implementation on the Temporary Data Storage Method for Cone Penetration Test.

Sensors (Basel) 2021 Jan 15;21(2). Epub 2021 Jan 15.

College of Geology Engineering and Geomatics, Chang'an University, Xi'an 710054, China.

The traditional cone penetration test system uses cable to transmit data; as the probe goes deeper into the ground, the length of the cable will become longer. This makes the installation of the test equipment more complicated, and excessively long cables cause signal distortion and seriously affect data accuracy. To simplify the experimental equipment and improve the accuracy of data acquisition, a cableless cone penetration test system is proposed. The improved system uses an SD card to store the experimental data, as opposed to using cables for communication which, often lead to the distortion of signals caused by long-distance communication and data loss caused by accidental cable breaks. Therefore, the accuracy of the collected data is higher, and the experimental device is simplified. To evaluate the applicability and efficiency of our design, we have carried out exploration experiments with the sensor system proposed in this paper. The test results show that the experimental data collected by the new system are basically consistent with the data collected by traditional cable CPT equipment, and the accuracy of the collected data is higher. It is more reliable and accurate to analyze the comprehensive mechanical properties of the soil layers with the data collected by the new system.
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http://dx.doi.org/10.3390/s21020575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830836PMC
January 2021

Exome Chip Analyses and Genetic Risk for IgA Nephropathy among Han Chinese.

Clin J Am Soc Nephrol 2021 02 18;16(2):213-224. Epub 2021 Jan 18.

Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People's Republic of China

Background And Objectives: IgA nephropathy is the most common form of primary GN worldwide. The evidence of geographic and ethnic differences, as well as familial aggregation of the disease, supports a strong genetic contribution to IgA nephropathy. Evidence for genetic factors in IgA nephropathy comes also from genome-wide association patient-control studies. However, few studies have systematically evaluated the contribution of coding variation in IgA nephropathy.

Design, Setting, Participants, & Measurements: We performed a two-stage exome chip-based association study in 13,242 samples, including 3363 patients with IgA nephropathy and 9879 healthy controls of Han Chinese ancestry. Common variant functional annotation, gene-based low-frequency variants analysis, differential mRNA expression, and gene network integration were also explored.

Results: We identified three non-HLA gene regions (, , and ) and one HLA gene region () with suggestive significance ( <5×10) in single-variant associations. These novel non-HLA variants were annotated as expression-associated single-nucleotide polymorphisms and were located in enhancer regions enriched in histone marks H3K4me1 in primary B cells. Gene-based low-frequency variants analysis suggests as another potential susceptibility gene. Further combined expression and network integration suggested that the five novel susceptibility genes, , , , , and , were involved in IgA nephropathy.

Conclusions: Five novel gene regions with suggestive significance for IgA nephropathy were identified and shed new light for further mechanism investigation.
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http://dx.doi.org/10.2215/CJN.06910520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863642PMC
February 2021

Exome-wide evaluation of rare coding variants using electronic health records identifies new gene-phenotype associations.

Nat Med 2021 01 11;27(1):66-72. Epub 2021 Jan 11.

Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

The clinical impact of rare loss-of-function variants has yet to be determined for most genes. Integration of DNA sequencing data with electronic health records (EHRs) could enhance our understanding of the contribution of rare genetic variation to human disease. By leveraging 10,900 whole-exome sequences linked to EHR data in the Penn Medicine Biobank, we addressed the association of the cumulative effects of rare predicted loss-of-function variants for each individual gene on human disease on an exome-wide scale, as assessed using a set of diverse EHR phenotypes. After discovering 97 genes with exome-by-phenome-wide significant phenotype associations (P < 10), we replicated 26 of these in the Penn Medicine Biobank, as well as in three other medical biobanks and the population-based UK Biobank. Of these 26 genes, five had associations that have been previously reported and represented positive controls, whereas 21 had phenotype associations not previously reported, among which were genes implicated in glaucoma, aortic ectasia, diabetes mellitus, muscular dystrophy and hearing loss. These findings show the value of aggregating rare predicted loss-of-function variants into 'gene burdens' for identifying new gene-disease associations using EHR phenotypes in a medical biobank. We suggest that application of this approach to even larger numbers of individuals will provide the statistical power required to uncover unexplored relationships between rare genetic variation and disease phenotypes.
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http://dx.doi.org/10.1038/s41591-020-1133-8DOI Listing
January 2021

Anlotinib enhances the antitumor activity of radiofrequency ablation on lung squamous cell carcinoma.

Pharmacol Res 2021 02 7;164:105392. Epub 2021 Jan 7.

Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, PR China. Electronic address:

Anlotinib is a novel molecular targeted drug that has been approved for the treatment of lung adenocarcinoma. Currently these agents are rarely used in the treatment of lung squamous cell carcinoma (LSCC). Bronchoscope-guided radiofrequency ablation (RFA) is a new strategy proposed for the treatment of LSCC that is able to alleviate the obstruction of the respiratory tract caused by LSCC by direct destruction of the tumor tissues. The presence work aims to reveal whether Anlotinib could enhance the antitumor activity of RFA on LSCC cells. The results from real-time PCR (qPCR) confirmed overexpression of targets of anlotinib activity, including receptor tyrosine kinase or the MPAK/PI3K-AKT pathway kinases, in LSCC tissues. Treatment with anlotinib inhibited the survival, in vitro invasion, and migration of LSCC cells. Moreover, the antitumor effects of RFA were investigated using a rodent model of LSCC. The combination of RFA and anlotinib treatment enhanced the antitumor effect of RFA treatment. We propose a combinative strategy of RFA and anlotinib as a novel approach for successful management of LSCC.
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http://dx.doi.org/10.1016/j.phrs.2020.105392DOI Listing
February 2021

Cryptococcemia According to Immune Status: An Analysis of 65 Critical Cases.

Infect Dis Ther 2021 Mar 16;10(1):363-371. Epub 2020 Dec 16.

Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Introduction: Cryptococcemia is associated with poor prognosis among patients with cryptococcosis. However, there are limited data on the clinical features of cryptococcemia, particularly among patients with different immune statuses. This study assessed the largest number of cases diagnosed with cryptococcemia, to the best of our knowledge.

Methods: Demographic and clinical data of patients with positive blood culture results for Cryptococcus were obtained from medical records at the Xiangya Hospital (2010-2019).

Results: A total of 65 patients were diagnosed and treated for cryptococcemia, of which 53 (82%) immunosuppressed patients were afflicted with HIV (12%, 8/65), tuberculosis (8%, 5/26), liver cirrhosis (6%, 3/65), chronic renal failure (6%, 3/65), nephrotic syndrome (13%, 7/65), systemic lupus erythematosus (8%, 5/65), chronic glomerulonephritis (11%, 6/65), malignant diseases (19%, 10/65), and diabetes (11%, 6/65). Most patients (85%, 55/65) presented with fever. Other symptoms, such as cough, headache, enlarged lymph nodes, liver, or spleen, and septic shock, were also reported. Typically, the sites of infection included the central nervous system, lung, skin, bone, abdomen, endometrium, lymph node, and blood. Although early systemic antifungal therapy was administered to 61 patients within 48 h of hospitalization, the 60-day mortality rate was higher in the immunosuppressed group (53%) than in the immunocompetent group (8%).

Conclusions: Our study indicated that patients with different immune statuses presented different clinical features. Immunosuppressed patients with cryptococcemia presented a higher risk of mortality with poor prognosis, which required intense attention and treatment in time.
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http://dx.doi.org/10.1007/s40121-020-00375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954890PMC
March 2021

Wnt3a upregulation is involved in TGFβ1-induced cardiac hypertrophy.

Cytokine 2021 02 23;138:155376. Epub 2020 Nov 23.

Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan Province 475000, China. Electronic address:

Pathological cardiac hypertrophy, characterized by enlarged cell size and fetal gene reactivation, ultimately leads to cardiac dysfunction and heart failure. The expression of transforming growth factor beta 1 (TGFβ1) is often elevated in experimental models of cardiac hypertrophy. In the present study, we observed the activation of Wnt/β-catenin signaling in TGFβ1-induced cardiac hypertrophy. TGFβ1 stimulation decreased the phosphorylation levels of β-catenin and triggered the nuclear accumulation of β-catenin. In turn, TGFβ1 enhanced the expression of c-Myc, which is a transcriptional target of canonical Wnt/β-catenin pathway. Knockdown of β-catenin completely blocked TGFβ1-induced c-Myc upregulation. Wnt3a is an important Wnt ligand associated with cardiac fibrosis and hypertrophy. Further investigation revealed that TGFβ1 can upregulate Wnt3a expression in an ALK5-Smad2/3-dependent manner. A consensus Smad binding sequence is located within the Wnt3a promoter, and TGFβ1 stimulation enhanced recruitment of Smad2/3 onto the Wnt3a promoter. Meanwhile, Wnt3a overexpression also stimulated TGFβ1 expression. Chemical inhibition of Wnt/β-catenin signaling partially attenuated TGFβ1-induced hypertrophic responses. These findings suggest crosstalk between TGFβ1 and canonical Wnt/β-catenin pathways in cardiac hypertrophy.
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http://dx.doi.org/10.1016/j.cyto.2020.155376DOI Listing
February 2021

Cholesterol-Induced Phenotypic Modulation of Smooth Muscle Cells to Macrophage/Fibroblast-like Cells Is Driven by an Unfolded Protein Response.

Arterioscler Thromb Vasc Biol 2021 01 8;41(1):302-316. Epub 2020 Oct 8.

Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX (A.C., C.S.K., K.K., A.K., J.C., D.M.M.).

Objective: Vascular smooth muscle cells (SMCs) dedifferentiate and initiate expression of macrophage markers with cholesterol exposure. This phenotypic switching is dependent on the transcription factor Klf4 (Krüppel-like factor 4). We investigated the molecular pathway by which cholesterol induces SMC phenotypic switching. Approach and Results: With exposure to free cholesterol, SMCs decrease expression of contractile markers, activate Klf4, and upregulate a subset of macrophage and fibroblast markers characteristic of modulated SMCs that appear with atherosclerotic plaque formation. These phenotypic changes are associated with activation of all 3 pathways of the endoplasmic reticulum unfolded protein response (UPR), Perk (protein kinase RNA-like endoplasmic reticulum kinase), Ire (inositol-requiring enzyme) 1α, and Atf (activating transcription factor) 6. Blocking the movement of cholesterol from the plasma membrane to the endoplasmic reticulum prevents free cholesterol-induced UPR, Klf4 activation, and upregulation of the majority of macrophage and fibroblast markers. Cholesterol-induced phenotypic switching is also prevented by global UPR inhibition or specific inhibition of Perk signaling. Exposure to chemical UPR inducers, tunicamycin and thapsigargin, is sufficient to induce these same phenotypic transitions. Finally, analysis of published single-cell RNA sequencing data during atherosclerotic plaque formation in hyperlipidemic mice provides preliminary in vivo evidence of a role of UPR activation in modulated SMCs.

Conclusions: Our data demonstrate that UPR is necessary and sufficient to drive phenotypic switching of SMCs to cells that resemble modulated SMCs found in atherosclerotic plaques. Preventing a UPR in hyperlipidemic mice diminishes atherosclerotic burden, and our data suggest that preventing SMC transition to dedifferentiated cells expressing macrophage and fibroblast markers contributes to this decreased plaque burden.
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http://dx.doi.org/10.1161/ATVBAHA.120.315164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752246PMC
January 2021

Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue.

Circulation 2020 10 5;142(14):1374-1388. Epub 2020 Oct 5.

Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery (Yanming Li, P.R., A. Dawson, H.G.V., W.A., C.Z., W.L., J.S.C., Y.H.S., S.A.L.), Baylor College of Medicine, Houston, TX.

Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues.

Methods: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies.

Results: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene() exerts an important role in maintaining normal aortic wall function.

Conclusions: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539140PMC
October 2020

Effects of carbon-based additives and ventilation rate on nitrogen loss and microbial community during chicken manure composting.

PLoS One 2020 23;15(9):e0229880. Epub 2020 Sep 23.

Shandong Academy of Agricultural Machinery Sciences, Jinan, Shandong Province, China.

Aerobic composting is a sustainable method for chicken manure recycling, while its unsuitable porosity and carbon to nitrogen ratio (C/N) may result in high nitrogen loss and incomplete composting. With the aim to investigate the effects of carbon-based additives and two ventilation rates on chicken manure composting and microbial community, two series of treatments were set up for chicken manure composting, in order to investigate their effects on the biodegradation process, ammonia (NH3) emission, nitrogen loss, physiochemical properties and microbial community. The results showed that additives and ventilation rates set in the current study influenced the carbon dioxide (CO2) production from the 2nd week and also the physiochemical parameters during the entire process, while no inhibitory effect on the maturity were observed. With woody peat as additive, the NH3 emission amount and nitrogen loss rate were shown as 15.86 mg and 4.02%, less than those in other treatments, 31.08-80.13 mg and 24.26-34.24%, respectively. The high aeration rate increased the NH3 emission and nitrogen loss, which were varied when the additives were different. The terminal restriction fragment length polymorphism (T-RFLP) results showed that the additives and the ventilation rates changed the microbial community, while the prominent microbial clones belonged to the class of Bacilli and Clostridia (in the phylum of Firmicutes), and Alphaproteobacteria, Deltaproteobacteria and Gammaproteobacteria (in the phylum of Proteobacteria). Bacillus spp. was observed to be the most dominant bacteria in all the composting stages and treatments. It was concluded that woody peat could improve chicken manure composting more than other additives, especially on reducing nitrogen loss, meanwhile 0.18 L‧min-1‧kg-1 DM was suitable for various additives. Therefore, suitable additive and aeration rate could be used in practical application, which could significantly reduce nitrogen loss without influence on the compos maturity process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229880PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511025PMC
October 2020

Hypoxia exacerbates cardiomyocyte injury via upregulation of Wnt3a and inhibition of Sirt3.

Cytokine 2020 12 17;136:155237. Epub 2020 Aug 17.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address:

Ischemic injury is a major cause of several cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy, and ventricular remodeling. Using an in vitro hypoxia model to mimic ischemia, we found that hypoxia stimulated Wnt3a expression. A mechanistic study showed that hypoxia-inducible factor 1α (HIF-1α) was directly recruited to the Wnt3a promoter. Wnt3a overexpression significantly decreased cell viability, promoted the generation of apoptotic cells, and enhanced hypoxia-induced injury in neonatal rat cardiomyocytes. This was partially through the upregulation of Caspase-3 mRNA levels and cleaved PARP-1 protein levels. In addition, we observed that Wnt3a exacerbated hypoxia-induced mitochondrial dysfunction and cytosolic release of cytochrome C. Furthermore, we found that Sirt3, a mitochondrial NAD-dependent deacetylase that modulates mitochondrial metabolism and homeostasis, was negatively regulated by Wnt3a. Conversely, Sirt3 overexpression repressed Wnt3a expression and ameliorated the hypoxia-induced mitochondrial dysfunction. Overall, our findings suggest that the hypoxia-Wnt3a-Sirt3 regulatory axis might be a potential target for cell protection in cardiac ischemia and hypoxia.
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http://dx.doi.org/10.1016/j.cyto.2020.155237DOI Listing
December 2020
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