Publications by authors named "Bo Hu"

1,378 Publications

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Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis.

J Mol Med (Berl) 2021 Aug 3. Epub 2021 Aug 3.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Atherosclerosis is a chronic and progressive process. It is the most important pathological basis of cardiovascular disease and stroke. Vascular smooth muscle cells (VSMCs) are an essential cell type in atherosclerosis. Previous studies have revealed that VSMCs undergo phenotypic transformation in atherosclerosis to participate in the retention of atherogenic lipoproteins as well as the formation of the fibrous cap and the underlying necrotic core in plaques. The emergence of lineage-tracing studies indicates that the function and number of VSMCs in plaques have been greatly underestimated. In addition, recent studies have revealed that VSMCs make up at least 50% of the foam cell population in human and mouse atherosclerotic lesions. Therefore, understanding the formation of lipid-loaded VSMCs and their regulatory mechanisms is critical to elucidate the pathogenesis of atherosclerosis and to explore potential therapeutic targets. Moreover, combination of many complementary technologies such as lineage tracing, single-cell RNA sequencing (scRNA-seq), flow cytometry, and mass cytometry (CyTOF) with immunostaining has been performed to further understand the complex VSMC function. Correct identification of detrimental and beneficial processes may reveal successful therapeutic treatments targeting VSMCs and their derivatives during atherosclerosis. The purpose of this review is to summarize the process of lipid-loaded VSMC formation in atherosclerosis and to describe novel insight into VSMCs gained by using multiple advanced methods.
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http://dx.doi.org/10.1007/s00109-021-02109-8DOI Listing
August 2021

Patient-Derived Xenograft Models for Intrahepatic Cholangiocarcinoma and Their Application in Guiding Personalized Medicine.

Front Oncol 2021 13;11:704042. Epub 2021 Jul 13.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.

Background: Intrahepatic cholangiocarcinoma (ICC) remains one of the most intractable malignancies. The development of effective drug treatments for ICC is seriously hampered by the lack of reliable tumor models. At present, patient derived xenograft (PDX) models prove to accurately reflect the genetic and biological diversity required to decipher tumor biology and therapeutic vulnerabilities. This study was designed to investigate the establishment and potential application of PDX models for guiding personalized medicine and identifying potential biomarker for lenvatinib resistance.

Methods: We generated PDX models from 89 patients with ICC and compared the morphological and molecular similarities of parental tumors and passaged PDXs. The clinicopathologic features affecting PDX engraftment and the prognostic significance of PDX engraftment were analyzed. Drug treatment responses were analyzed in IMF-138, IMF-114 PDX models and corresponding patients. Finally, lenvatinib treatment response was examined in PDX models and potential drug resistance mechanism was revealed.

Results: Forty-nine PDX models were established (take rate: 55.1%). Successful PDX engraftment was associated with negative HbsAg (P = 0.031), presence of mVI (P = 0.001), poorer tumor differentiation (P = 0.023), multiple tumor number (P = 0.003), presence of lymph node metastasis (P = 0.001), and later TNM stage (P = 0.039). Moreover, patients with tumor engraftment had significantly shorter time to recurrence (TTR) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis indicated that PDX engraftment was an independent risk factor for shortened TTR (HR = 1.84; 95% CI, 1.05-3.23; P = 0.034) and OS (HR = 2.13; 95% CI, 1.11-4.11; P = 0.024). PDXs were histologically and genetically similar to their parental tumors. We also applied IMF-138 and IMF-114 PDX drug testing results to guide clinical treatment for patients with ICC and found similar treatment responses. PDX models also facilitated personalized medicine for patients with ICC based on drug screening results using whole exome sequencing data. Additionally, PDX models reflected the heterogeneous sensitivity to lenvatinib treatment and CDH1 might be vital to lenvatinib-resistance.

Conclusion: PDX models provide a powerful platform for preclinical drug discovery, and potentially facilitate the implementation of personalized medicine and improvement of survival of ICC cancer patient.
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http://dx.doi.org/10.3389/fonc.2021.704042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315044PMC
July 2021

Advances in forensic diagnosis of electric shock death in the absence of typical electrical marks.

Int J Legal Med 2021 Jul 27. Epub 2021 Jul 27.

Forensic and Pathology Laboratory, Judicial Expertise Center, Jiaxing University Medical College, Jiaxing, 314001, ZJ, China.

Electrical injury is a relatively uncommon but potentially devastating form of multi-system injury with high morbidity and mortality. In common electric injury cases, it is usually difficult to find characteristic changes of electric injury in major organs by using routine histopathological test methods unless there are landmark traces of electric injury, known as electric marks. How to determine electric shock death, especially in the absence of typical electrical marks on the body surface in some cases (which account for about two-thirds of electric injury cases), remains a challenging problem in forensic practice. Our summary shows that many current related studies have focused their efforts to find characteristic histopathological changes in major organs of the body caused by electric injury. Based on the results obtained through comparison of the literature, we find that it may be more urgent and important to find the optimal autopsy or sampling sites in cases with no typical electric marks, knowing that these sites may often reflect the most significant histopathological changes of electric injury, for instance anatomy and sampling of the anterior wrist and the medial malleolus in cases involving the hand-to-foot electric circuit pathway. In this article, we make a summary of advances in identification methods of electric injury, hoping that it could provide some new insights for further research in this field.
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http://dx.doi.org/10.1007/s00414-021-02658-0DOI Listing
July 2021

Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers.

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

Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Uveal melanoma metastases are lethal and remain incurable. A quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary uveal melanoma (pUM) was pursued for insights into UM metastasis and protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology. LC MS/MS iTRAQ technology, the Mascot search engine, and the UniProt human database were used to identify and quantify pUM proteins relative to the normal choroid excised from UM donor eyes. The determined proteomes of all 100 tumors were very similar, encompassing a total of 3935 pUM proteins. Proteins differentially expressed (DE) between metastasizing and non-metastasizing pUM ( = 402) were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. The immune proteins ( = 778) identified in this study support the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as possible candidates for immune therapy checkpoint blockade. Prediction modeling identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy, supporting the potential for protein-based prognostic methods for detecting UM metastasis.
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http://dx.doi.org/10.3390/cancers13143520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307952PMC
July 2021

Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension.

Sci Rep 2021 Jul 19;11(1):14714. Epub 2021 Jul 19.

Departments of Inflammation and Immunity, Lerner Research Institute and Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave, NB20, Cleveland, OH, 44195, USA.

Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diversity among endothelial cells in the healthy pulmonary vascular bed and the pathologic diversity among pulmonary arterial endothelial cells (PAEC) in PAH is unknown and previously unexplored. Here single-cell RNA sequencing technology was used to decipher the cellular heterogeneity among PAEC in the human pulmonary arteries isolated from explanted lungs from three patients with PAH undergoing lung transplantation and three healthy donor lungs not utilized for transplantation. Datasets of 36,368 PAH individual endothelial cells and 36,086 healthy cells were analyzed using the SeqGeq bioinformatics program. Total population differential gene expression analyses identified 629 differentially expressed genes between PAH and controls. Gene Ontology and Canonical Ingenuity analysis revealed pathways that are known to be involved in pathogenesis, as well as unique new pathways. At the individual cell level, dimensionality reduction followed by density based clustering revealed the presence of eight unique PAEC clusters that were typified by proliferative, angiogenic or quiescent phenotypes. While control and PAH harbored many similar subgroups of endothelial cells, PAH had greater proportions of angiogenic and proliferative subsets. These findings identify that only specific subgroups of PAH PAEC have gene expression different than healthy PAEC, and suggest these subpopulations lead to the pathologic functions leading to remodeling.
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http://dx.doi.org/10.1038/s41598-021-94163-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289993PMC
July 2021

Primary Care Health Care Use for Patients With Type 2 Diabetes During the COVID-19 Pandemic.

Diabetes Care 2021 Jul 14. Epub 2021 Jul 14.

Center for Value-Based Care Research, Cleveland Clinic Community Care, Cleveland, OH.

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http://dx.doi.org/10.2337/dc21-0853DOI Listing
July 2021

Catastrophic health expenditure and mental health in the older Chinese population: The moderating role of social health insurance.

Authors:
Wei Yang Bo Hu

J Gerontol B Psychol Sci Soc Sci 2021 Jul 13. Epub 2021 Jul 13.

Care Policy and Evaluation Centre (CPEC), Department of Health Policy, The London School of Economics and Political Science.

Objectives: Catastrophic health expenditure (CHE) has considerable effects on household living standards, but little is known regarding the relationships between CHE and people's mental health. Using China as an example, this study examines the association between CHE and mental health and investigates whether the association differs between those with and without social health insurance (SHI).

Methods: The data came from three waves of the China Health and Retirement Longitudinal Study (CHARLS 2011, 2013, and 2015, N = 13,166). We focused on older people aged 60 and above. We built panel data regression and quantile regression models to analyse the data.

Results: Incurring CHE is significantly associated with poor mental health. The association is weakened among older people receiving SHI, which indicates that SHI has a protective effect. Moreover, the association between CHE and mental health and the protective effect of SHI are stronger among those with mild or moderate mental health problems.

Discussion: Our findings provide empirical evidence that encourages the integration of psychologically informed approaches in health services. We also urge governments in low- and middle-income countries to consider more generous health financing mechanisms for older people with greater healthcare needs.
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http://dx.doi.org/10.1093/geronb/gbab130DOI Listing
July 2021

Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?

Front Immunol 2021 23;12:678744. Epub 2021 Jun 23.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immune cells (microglia, astrocytes, and pericytes) on BBB disruption have been underestimated in ischemic stroke. Post-stroke microglia and astrocytes can adopt both an M1/A1 or M2/A2 phenotype, which influence BBB integrity differently. However, whether pericytes acquire microglia phenotype and exert immunological effects on the BBB remains controversial. Thus, better understanding the inflammatory mechanism underlying BBB disruption can lead to the identification of more promising biological targets to develop treatments that minimize the onset of life-threatening complications and to improve existing treatments in patients. However, early attempts to inhibit the infiltration of circulating immune cells into the brain by blocking adhesion molecules, that were successful in experimental stroke failed in clinical trials. Therefore, new immunoregulatory therapeutic strategies for acute ischemic stroke are desperately warranted. Herein, we highlight the role of circulating and cerebral immune cells in BBB disruption and the crosstalk between them following acute ischemic stroke. Using a robust theoretical background, we discuss potential and effective immunotherapeutic targets to regulate BBB permeability after acute ischemic stroke.
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http://dx.doi.org/10.3389/fimmu.2021.678744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260997PMC
June 2021

Unsupervised Hierarchical Clustering Identifies Immune Gene Subtypes in Gastric Cancer.

Front Pharmacol 2021 24;12:692454. Epub 2021 Jun 24.

Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

The pathogenesis of heterogeneity in gastric cancer (GC) is not clear and presents as a significant obstacle in providing effective drug treatment. We aimed to identify subtypes of GC and explore the underlying pathogenesis. We collected two microarray datasets from GEO (GSE84433 and GSE84426), performed an unsupervised cluster analysis based on gene expression patterns, and identified related immune and stromal cells. Then, we explored the possible molecular mechanisms of each subtype by functional enrichment analysis and identified related hub genes. First, we identified three clusters of GC by unsupervised hierarchical clustering, with average silhouette width of 0.96, and also identified their related representative genes and immune cells. We validated our findings using dataset GSE84426. Subtypes associated with the highest mortality (subtype 2 in the training group and subtype C in the validation group) showed high expression of SPARC, COL3A1, and CCN. Both subtypes also showed high infiltration of fibroblasts, endothelial cells, hematopoietic stem cells, and a high stromal score. Furthermore, subtypes with the best prognosis (subtype 3 in the training group and subtype A in the validation group) showed high expression of FGL2, DLGAP1-AS5, and so on. Both subtypes also showed high infiltration of CD4 T cells, CD8 T cells, NK cells, pDC, macrophages, and CD4 T effector memory cells. We found that GC can be classified into three subtypes based on gene expression patterns and cell composition. Findings of this study help us better understand the tumor microenvironment and immune milieu associated with heterogeneity in GC and provide practical information to guide personalized treatment.
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http://dx.doi.org/10.3389/fphar.2021.692454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264374PMC
June 2021

Arbuscular mycorrhizal symbiosis in constructed wetlands with different substrates: Effects on the phytoremediation of ibuprofen and diclofenac.

J Environ Manage 2021 Jul 9;296:113217. Epub 2021 Jul 9.

Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, Praha-Suchdol, 16500, Czech Republic. Electronic address:

This study investigated the role of arbuscular mycorrhizal fungal (AMF) for the removal of ibuprofen (IBU) and diclofenac (DCF) in constructed wetlands (CWs) with four different substrates. Results showed that AMF colonization in adsorptive substrate (perlite, vermiculite, and biochar) systems was higher than that in sand systems. AMF enhanced the tolerance of Glyceria maxima to the stress of IBU and DCF by promoting the activities of antioxidant enzymes (peroxidase and superoxide dismutase) and the contents of soluble protein, while decreasing the contents of malondialdehyde and O. The removal efficiencies of IBU and DCF were increased by 15%-18% and 25%-38% in adsorptive substrate systems compare to sand systems. Adsorptive substrates enhanced the accumulation of IBU and DCF in the rhizosphere and promoted the uptake of IBU and DCF by plant roots. AMF promoted the removal of IBU and DCF in sand systems but limited their reduction in adsorptive substrate systems. In all scenarios, the presence of AMF decreased the contents of CECs metabolites (2-OH IBU, CA IBU, and 4'-OH IBU) in the effluents and promoted the uptake of IBU by plant roots. Therefore, these results indicated that the addition of adsorptive substrates could enhance the removal of IBU and DCF in CWs. The role of AMF on the removal of IBU and DCF was influenced by CW substrate. These may provide useful information for the application of AMF in CWs to remove contaminants of emerging concern.
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http://dx.doi.org/10.1016/j.jenvman.2021.113217DOI Listing
July 2021

Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy.

Pharmacol Res 2021 Jul 3;171:105755. Epub 2021 Jul 3.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.
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http://dx.doi.org/10.1016/j.phrs.2021.105755DOI Listing
July 2021

An analysis of delay-constrained consensus-based optimal algorithms in virtual power plants.

ISA Trans 2021 Jun 28. Epub 2021 Jun 28.

State Key Laboratory of Power Transmission Equipment and System Security at Chongqing University, Chongqing 400044, China. Electronic address:

In virtual power plants (VPPs), consensus-based distributed optimal dispatch algorithms aim to collectively minimize the operating cost. As ubiquitous latency on communication networks may lead to divergence, convergence to a nonoptimal solution, or a longer convergence time, mitigating the impacts of arbitrarily large but bounded time-varying delays is significant both in theory and in practice. To modify a typical consensus-based optimal dispatch algorithm under time-varying delays, this paper designs new update rules and introduces a reduction approach to evaluate the performance of the algorithm. The results reveal that the modified algorithm can always converge to the optimal solution with a tactical initial setup in a distributed manner if the undirected interaction topology is connected and the gain parameter is sufficiently small. The analytical expression of the gain is also given. Furthermore, we show that the convergence time is determined by the maximum time delays, the number of generators, and the convergence accuracy. Several numerical simulation studies validate our theory.
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http://dx.doi.org/10.1016/j.isatra.2021.06.035DOI Listing
June 2021

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Nat Commun 2021 07 2;12(1):4091. Epub 2021 Jul 2.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.
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http://dx.doi.org/10.1038/s41467-021-24386-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253833PMC
July 2021

Integrative analysis of histomorphology, transcriptome and whole genome resequencing identified DIO2 gene as a crucial gene for the protuberant knob located on forehead in geese.

BMC Genomics 2021 Jun 30;22(1):487. Epub 2021 Jun 30.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, 611130, Chengdu, China.

Background: During domestication, remarkable changes in behavior, morphology, physiology and production performance have taken place in farm animals. As one of the most economically important poultry, goose owns a unique appearance characteristic called knob, which is located at the base of the upper bill. However, neither the histomorphology nor the genetic mechanism of the knob phenotype has been revealed in geese.

Results: In the present study, integrated radiographic, histological, transcriptomic and genomic analyses revealed the histomorphological characteristics and genetic mechanism of goose knob. The knob skin was developed, and radiographic results demonstrated that the knob bone was obviously protuberant and pneumatized. Histologically, there were major differences in structures in both the knob skin and bone between geese owing knob (namely knob-geese) and those devoid of knob (namely non-knob geese). Through transcriptome analysis, 592 and 952 genes differentially expressed in knob skin and bone, and significantly enriched in PPAR and Calcium pathways in knob skin and bone, respectively, which revealed the molecular mechanisms of histomorphological differences of the knob between knob- and non-knob geese. Furthermore, integrated transcriptomic and genomic analysis contributed to the identification of 17 and 21 candidate genes associated with the knob formation in the skin and bone, respectively. Of them, DIO2 gene could play a pivotal role in determining the knob phenotype in geese. Because a non-synonymous mutation (c.642,923 G > A, P265L) changed DIO2 protein secondary structure in knob geese, and Sanger sequencing further showed that the AA genotype was identified in the population of knob geese, and was prevalent in a crossing population which was artificially selected for 10 generations.

Conclusions: This study was the first to uncover the knob histomorphological characteristics and genetic mechanism in geese, and DIO2 was identified as the crucial gene associated with the knob phenotype. These data not only expand and enrich our knowledge on the molecular mechanisms underlying the formation of head appendages in both mammalian and avian species, but also have important theoretical and practical significance for goose breeding.
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http://dx.doi.org/10.1186/s12864-021-07822-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244220PMC
June 2021

The chromosome-level genome of Triplophysa dalaica (Cypriniformes: Cobitidae) provides insights into its survival in extremely alkaline environment.

Genome Biol Evol 2021 Jun 29. Epub 2021 Jun 29.

College of Fisheries, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang 453007, Henan, China.

Lake Dali Nur, located in Inner Mongolia, North China, is alkaline, with Triplophysa dalaica one of the three fish species that not only survive, but thrive, in the lake. To investigate the presence of molecular mutations potentially responsible for this adaptation, the whole genome sequence of the species was sequenced. A total of 126.5 Gb and 106 Gb data, covering nearly 200X of the estimated genome, were generated using long-read sequencing and Hi-C technology, respectively. De novo assembly generated a genome totalled 607.91 Mb, with a contig N50 of 9.27 Mb. Nearly all whole genome sequences were anchored and oriented onto 25 chromosomes, with telomeres for most chromosomes also being recovered. Repeats comprised approximately 35.01% of the whole genome. A total of 23,925 protein-coding genes were predicted, within which, 98.62% could be functionally annotated. Through comparisons of T. dalaica, T. tibetana, and T. siluroides gene models, a total of 898 genes were identified as likely being subjected to positive selection, with several of them potentially associated with alkaline adaptation, such as sodium bicarbonate cotransporter, SLC4A4. Demographic analyses suggested that the Dali population might have diverged from endemic freshwater Hai River populations, approximately 1 million years ago. The high-quality T. dalaica genome, created in this study, not only aids in the analyses of alkaline adaptation, but may also assist in revealing the mysteries of the highly divergent genus Triplophysa in the future.
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http://dx.doi.org/10.1093/gbe/evab153DOI Listing
June 2021

An L0 regularization method for imaging genetics and whole genome association analysis on Alzheimer's disease.

IEEE J Biomed Health Inform 2021 Jun 28;PP. Epub 2021 Jun 28.

Although the neuroimaging measures build a bridge between genetic variants and disease phenotype, an assessment of single nucleotide variants changes in brain structure and their clinically influence on the progression of Alzheimers disease remain largely preliminary. Note that each variant has very weak correlation signal to neuroimaging measures or Alzheimers disease phenotype. Therefore, traditional sparse regression-based image genetics approaches confront with unresolvable features, relative high regression error or inapplicability of high-dimensional data. Adopting an L0 regularization method, we significantly elevate the regression accuracy of imaging genetics compared with group-sparse multitask regression method. With further analysis on the simulation results, we conclude that multiple regression tasks model may be unsuitable for image genetics. In addition, we carried out a whole genome association analysis between genetic variants (about 388 million loci) and phenotype (cognition normal, mild cognitive impairment and Alzheimer's disease) with using the L0 regularization method. After annotating the effect of all variants by Ensembl Variant Effect Predictor (VEP), our method located 33 missense variants which can explain 40.1% phenotypevariance. Then, we mapped each missense variant to the nearest gene and carried out pathway enrichment analysis. The Notch signaling pathway and Apoptosis pathway have been reported to be related to the formation of Alzheimer's disease.
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http://dx.doi.org/10.1109/JBHI.2021.3093027DOI Listing
June 2021

Shared Medical Appointments and Prediabetes: The Power of the Group.

Ann Fam Med 2021 May-Jun;19(3):258-261

Center for Value-Based Care Research Cleveland Clinic, Cleveland, Ohio.

Shared medical appointments, which allow greater access to care and provide peer support, may be an effective treatment modality for prediabetes. We used a retrospective propensity-matched cohort analysis to compare patients attending a prediabetes shared medical appointment to usual care. Primary outcome was patient's weight change over 24 months. Secondary outcomes included change in hemoglobin A, low density lipoprotein, and systolic blood pressure. The shared medical appointments group lost more weight (2.88 kg vs 1.29 kg, = .003), and achieved greater reduction in hemoglobin A (-0.87% vs +0.87%, = .001) and systolic blood pressure (-4.35 mmHg vs +0.52 mmHg, = .044). The shared medical appointment model can be effective in treating prediabetes.
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http://dx.doi.org/10.1370/afm.2647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118487PMC
November 2019

Atovaquone at clinically relevant concentration overcomes chemoresistance in ovarian cancer via inhibiting mitochondrial respiration.

Pathol Res Pract 2021 Jun 19;224:153529. Epub 2021 Jun 19.

Department of Oncology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China. Electronic address:

The poor outcomes in ovarian cancer necessitate new treatments. Strategies to interfere with oxidative phosphorylation have been recently highlighted for the treatment of ovarian tumors. Atovaquone, an approved antimicrobial drug, has demonstrated anti-cancer potential and ability in disrupting mitochondrial function. Here, we investigated the efficacy of atovaquone as single drug and its combination with cisplatin in ovarian cancer. We show that atovaquone at clinically achievable concentrations is active against ovarian cancer bulky and stem-cell like cells via inhibiting growth and colony formation, and inducing caspase-dependent apoptosis. In contrast, atovaquone either does not or inhibits normal cells in a less extent than in ovarian cancer cells. Mechanism studies using multiple independent approaches demonstrate that atovaquone acts on ovarian cancer cells via decreasing mitochondrial complex III which results in mitochondrial respiration inhibition, energy reduction and oxidative stress. In line with in vitro findings, atovaquone alone at non-toxic dose is effective in inhibiting ovarian cancer growth in vivo, and its combination with cisplatin is synergistic. Our study suggests that atovaquone is a promising candidate to the treatment of ovarian cancer. Our work also supports the notion that mitochondrial respiration is a therapeutic target in ovarian cancer.
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http://dx.doi.org/10.1016/j.prp.2021.153529DOI Listing
June 2021

Trajectories of Opioid Coverage After Long-Term Opioid Therapy Initiation Among a National Cohort of US Veterans.

J Pain Res 2021 14;14:1745-1762. Epub 2021 Jun 14.

Division of Pharmaceutical Evaluation and Policy, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Purpose: The objective of this study was to identify the trajectories that patients take after initiating long-term opioid therapy (LTOT).

Materials And Methods: Using a retrospective cohort design, veterans with chronic non-cancer pain (CNCP) initiating LTOT were identified. Group-based trajectory models were used to identify opioid therapy trajectories based on days of opioid supply (primary outcome) and average daily morphine milligram equivalent dose (AMME; secondary outcome) in each 180-day period following initiation of LTOT.

Results: A total of 438,398 veterans with CNCP initiated LTOT. Nine trajectories were identified: 33.7% with persistent, high days covered, 17.7% with persistent, moderate days covered, 16.6% with slow, persistent days-covered reduction, 2.4% with days-covered reduction followed by increase, 4.6% with delayed days-covered reduction, 4.1% with rapid days-covered reduction, 10.9% with moderate-paced discontinuation, 3.4% with delayed discontinuation, and 6.5% with rapid discontinuation. Patients following discontinuation trajectories were more likely to be younger, persons of color, use more supportive services (eg, physical therapy), and received less opioid days' supply and lower doses prior to initiating LTOT as compared to patients following persistent opioid days-covered trajectories. AMME trajectories were similar to days-covered trajectories.

Conclusion: Among persons initiating LTOT, nine opioid trajectories emerged which can be broadly characterized into three main trajectory groups: persistent opioid therapy (2 trajectories), reductions in opioid therapy (4 trajectories), and discontinuation (3 trajectories). A majority of patients (51.4%) maintained persistent opioid therapy. Further research is needed to assess the risks of opioid-related adverse outcomes among the identified trajectories.
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http://dx.doi.org/10.2147/JPR.S308196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214015PMC
June 2021

Comparative efficacy of different types of antihypertensive drugs in reversing left ventricular hypertrophy as determined with echocardiography in hypertensive patients: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(25):e26455

Department of Ultrasound, Ningbo No. 1 Hospital, Ningbo, Zhejiang, China.

Background: Reversing left ventricular hypertrophy (LVH) can reduce the incidence of adverse cardiovascular events. The lack of direct comparison between different antihypertensive drugs cannot evaluate the superiority-inferiority differentiation of different antihypertensive drugs in reversing LVH. Therefore, the objective of this protocol for systematic review and meta-analysis was to compare the efficacy of different types of antihypertensive drugs in reversing LVH in hypertensive patients.

Methods: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. Studies were identified through systematic searches in June 2021 with no restrictions on date and time, language, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. The risk of bias assessment of the included studies was performed by two authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). All calculations were carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, United Kingdom).

Results: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.

Conclusion: We hypothesized that the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in antihypertensive therapy could achieve better efficacy in reversing LVH in hypertensive patients.
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http://dx.doi.org/10.1097/MD.0000000000026455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238335PMC
June 2021

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) activates Aryl hydrocarbon receptor (AhR) mediated ROS and NLRP3 inflammasome/p38 MAPK pathway inducing necrosis in cochlear hair cells.

Ecotoxicol Environ Saf 2021 Sep 17;221:112423. Epub 2021 Jun 17.

Forensic and Pathology Laboratory, Jiaxing University Medical College, Jiaxing 314001, ZJ, China; Department of Public Health, Jiaxing University Medical College, Jiaxing 314001, ZJ, China. Electronic address:

Tetrabromodiphenyl ether (BDE-47) is widely used as commercial flame retardants that can be released into the environment and finally enter human body through the food chain. It has been identified to generate neurotoxicity, but little is known about auditory damage and the underlying mechanism following BDE-47 exposure. This study aimed to assess the cell viability with BDE-47 concentration ranging from 0 to 150 μM in mouse organ of Corti-derived cell lines (HEI-OC1). Aryl hydrocarbon receptor (AhR) as an environmental sensor, reactive oxygen species (ROS), NLRP3 inflammasome and p38 MAPK pathways were detected. Results: (1) BDE-47 inhibited the viability in a time- and dose-dependent way in HEI-OC1 cells. Cell cycle was arrested in G1 phase by BDE-47; (2) Elevated intracellular ROS, LDH levels and necrosis were found, which was alleviated by pretreatment with ROS scavenger N-acetylcysteine (NAC); (3) AhR plays an essential role in ligand-regulated transcription factor activation by exogenous environmental compounds. We found increased expression of AhR and decreased downstream targets of CYP 1A1 and CYP 1B1 in BDE-47-treated HEI-OC1 cells, which was reversed by the AhR antagonist CH-223191 for 2 h before BDE-47 exposure. No significant change was detected in CYP 2B; (4) Enhanced expressions of NLRP3 and caspase-1 were induced by BDE-47, with up-regulations of both pro-inflammatory factors for IL-1β, IL-6 and TNF-α, and anti-inflammatory factors for IL-4, IL-10 and IL-13, but down-regulation for IL-1α; (5) Additionally, the p38 MAPK signaling pathway was activated with increased phosphorylation levels of MKK/3/6, p38 MAPK and NF-kB. Overall, our findings illustrate a role of AhR in ROS-induced necrosis of cochlear hair cells by BDE-47 exposure, in which NLRP3 inflammasome and p38 MAPK signaling pathways are activated. The current study first elucidates the sense of hearing damage induced by BDE-47, and cell-specific or mixture exposures in vivo or human studies are needed to confirm this association.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112423DOI Listing
September 2021

Epidemiological and clinical characteristics of respiratory viruses in 4403 pediatric patients from multiple hospitals in Guangdong, China.

BMC Pediatr 2021 06 17;21(1):284. Epub 2021 Jun 17.

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Acute respiratory infections (ARI) cause considerable morbidity and mortality worldwide, especially in children. Unfortunately, there are limited multi-center data on common viral respiratory infections in south China.

Methods: A total of 4403 nasal swabs were collected from children in 10 cities in Guangdong, China in 2019. Seven respiratory viruses, influenza A virus (IFA), influenza B virus (IFB), respiratory syncytial virus (RSV), adenoviruses (ADV) and parainfluenza virus types 1-3 (PIV1, PIV2 and PIV3), were detected by direct immunofluorescence antibody assay. The personal information and clinical characteristics were recorded and analyzed.

Results: The results showed that at least one virus was detected in 1099 (24.96 %) samples. The detection rates of RSV, IFA, ADV, PIV3, PIV1 and PIV2 were 7.13 % (314/4403), 5.31 % (234/4403), 4.02 % (177/4403), 3.04 % (134/4403), 1.70 % (75/4403) and 1.16 % (51/4403), respectively. The detection rate of RSV was highest in 0-6-month-old children at 18.18 % (106/583), while the detection rate of IFA was highest in 12-18-year-old children at 20.48 % (17/83). The total detection rates in winter and spring were 35.67 % (219/614) and 34.56 % (403/1166), higher than those in summer, 17.41 % (284/1631), and autumn, 19.46 % (193/992).

Conclusions: RSV and IFA were the main respiratory viruses in children. With increasing age the detection rate of RSV decreased in children, but the trends for the detection rates of IFA and IFB were the opposite. This study provided the viral etiology and epidemiology of pediatric patients with ARI in Guangdong, China.
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http://dx.doi.org/10.1186/s12887-021-02759-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212487PMC
June 2021

Aggravated ozone pollution in the strong free convection boundary layer.

Sci Total Environ 2021 Sep 15;788:147740. Epub 2021 May 15.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China; Center for Excellence in Urban Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Clarifying the relationship between meteorological factors and ozone can provide scientific support for ozone pollution prediction, but the effects of boundary layer meteorology, especially boundary layer height and turbulence, on ozone pollution are rarely studied. Here, ozone and its related meteorological factors were observed in summer in Shijiazhuang, a city with the most serious ozone pollution on the North China Plain. The forced and free convection boundary layers were classified using ground remote observations. After eliminating the forced convection condition, strong free convection conditions, exhibiting a high boundary layer height, high wind speed, strong turbulence and large-scale free convection velocity, were found to be beneficial for the aggravation of ozone pollution. Combined with the ozone profile detected by a tethered balloon, the ozone chemical budget was calculated using the differences in the column ozone concentrations between the morning and afternoon, and the results confirmed the impact of free convection intensity on ozone pollution. The change in ozone sensitivity from VOCs sensitivity to NOx sensitivity driven by strong free convection was the main reason for the deterioration of ozone pollution. This study clarified the impact of boundary layer meteorology on ozone and its sensitivity and has important practical significance for ozone pollution prevention and early warning.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147740DOI Listing
September 2021

Phenotypic differences in the inner ears of CBA/CaJ and C57BL/6J mice carrying missense and single base pair deletion mutations in the Cdh23 gene.

J Neurosci Res 2021 Jun 16. Epub 2021 Jun 16.

Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China.

Different mutations in the cadherin 23 (CDH23) gene in different genetic backgrounds have been linked to either syndromic or nonsyndromic forms of deafness in humans. We previously reported a progressive hearing loss (HL) mouse model, the Cdh23 mouse, which carries a 208T > C mutation causing an amino acid substitution at S70P in C57BL/6J mice. To investigate the differences in Cdh23 mutation-related HL in different genetic backgrounds, we used the CRISPR/Cas9 system to generate homozygous mice in the CBA/CaJ background that have the same base pair missense mutation (208T > C) (Cdh23 ) as Cdh23 mice in the C57BL/6J background or a single base pair deletion (235G) (Cdh23 ) in the Cdh23 gene at exon 5. The two mutant mice exhibit hearing impairment across a broad range of frequencies. The progression of HL in Cdh23 mice is slower than that in Cdh23 mice. We also found structural abnormalities in the stereocilia of cochlear hair cells in Cdh23 and Cdh23 mice. Cdh23 mice show signs of vestibular dysfunction in open field behavior and swimming tests. In addition, we observed hair bundle defects in vestibular hair cells in Cdh23 mice. Our results suggest an interaction between the erl locus and the C57BL/6J background that exacerbates HL in Cdh23 mice. Moreover, our study confirms that the Cdh23 gene is essential for normal hearing and balance. These two novel mutant mouse strains provide excellent models for studying CDH23 mutation-related deafness in humans.
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http://dx.doi.org/10.1002/jnr.24905DOI Listing
June 2021

Glypican 4 regulates planar cell polarity of endoderm cells by controlling the localization of Cadherin 2.

Development 2021 Jul 12;148(14). Epub 2021 Jul 12.

Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.

Noncanonical Wnt/planar cell polarity (Wnt/PCP) signaling has been implicated in endoderm morphogenesis. However, the underlying cellular and molecular mechanisms of this process are unclear. We found that, during convergence and extension (C&E) in zebrafish, gut endodermal cells are polarized mediolaterally, with GFP-Vangl2 enriched at the anterior edges. Endoderm cell polarity is lost and intercalation is impaired in the absence of glypican 4 (gpc4), a heparan-sulfate proteoglycan that promotes Wnt/PCP signaling, suggesting that this signaling is required for endodermal cell polarity. Live imaging revealed that endoderm C&E is accomplished by polarized cell protrusions and junction remodeling, which are impaired in gpc4-deficient endodermal cells. Furthermore, in the absence of gpc4, Cadherin 2 expression on the endodermal cell surface is increased as a result of impaired Rab5c-mediated endocytosis, which partially accounts for the endodermal defects in these mutants. These findings indicate that Gpc4 regulates endodermal planar cell polarity during endoderm C&E by influencing the localization of Cadherin 2. Thus, our study uncovers a new mechanism by which Gpc4 regulates planar cell polarity and reveals the role of Wnt/PCP signaling in endoderm morphogenesis.
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http://dx.doi.org/10.1242/dev.199421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313861PMC
July 2021

Fucoidan reduces lipid accumulation by promoting foam cell autophagy via TFEB.

Carbohydr Polym 2021 Sep 26;268:118247. Epub 2021 May 26.

Marine College, Shandong University, Weihai, Shandong, China. Electronic address:

Atherosclerotic cardiovascular disease became one of the major causes of morbidity and mortality worldwide. As a sulfated polysaccharide with anti-inflammatory and hypolipidemic activities, fucoidan can induce autophagy. We show here that fucoidan reduces lipid accumulation in foam cells, which is one of the causes of atherosclerosis. Further studies show that fucoidan promotes autophagy showed by the expression of p62/SQSTM1 and microtubule-associated protein light chain 3 (LC3) II, which can be blocked by autophagy inhibitors 3-MA and bafilomycin A1. In addition, the expression of transcription factor EB (TFEB), master regulator of autophagy and lysosome function, is upregulated after the treatment with fucoidan. Moreover, the knockout of TFEB with small interfering RNA suppressed the effect of fucoidan. Together, fucoidan reduces lipid accumulation in foam cells by enhancing autophagy through the upregulation of TFEB. In view of the role of foam cells in atherosclerosis, fucoidan can be valuable for the treatment of atherosclerosis.
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http://dx.doi.org/10.1016/j.carbpol.2021.118247DOI Listing
September 2021

Eddy covariance measurements of ozone flux above and below a southern subtropical forest canopy.

Sci Total Environ 2021 Jun 7;791:148338. Epub 2021 Jun 7.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, Fujian, China.

While extensive eddy covariance (EC) measurements of ozone (O) flux have been reported in American and European forests, such measurements in Asian forests are scarce. Here, we presented the first EC measurements of O flux at two levels (above and below the canopy) in a Chinese forest. Above the canopy, O always moved downward, with a maximum O flux intensity of -15 ~ -10 nmol m s occurring at 9:00-14:00 LT and a maximum O deposition velocity of 1.23 cm s occurring at 9:00 LT; both of these values fell to nearly 0 at night. The O deposition flux and O deposition velocity below the canopy were both lower than those above the canopy. This discrepancy reached the maximum at 9:00-15:00 local time (LT), with the O deposition flux and O deposition velocity below the canopy being approximately 35 and 42% of those above the canopy, respectively. The O flux was well correlated with the CO flux and the latent heat flux, suggesting the important role of stomatal uptake in O deposition. The O deposition velocity increased with the increase in the air temperature, relative humidity, photosynthetically active radiation and friction velocity, but when these meteorological factors exceeded their optimum values, the increase in the O deposition velocity tended to be flat. These findings advanced our understanding of the interactions between forests and the atmosphere. This unique dataset is also of great significance for the validation of relevant models concerned with the various impacts of the rapid increase in global O concentrations.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148338DOI Listing
June 2021

The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis.

Front Cardiovasc Med 2021 28;8:682389. Epub 2021 May 28.

Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

Low-density lipoprotein receptor-related protein-1 (LRP1) is a large endocytic and signaling receptor belonging to the LDL receptor (LDLR) gene family and that is widely expressed in several tissues. LRP1 comprises a large extracellular domain (ECD; 515 kDa, α chain) and a small intracellular domain (ICD; 85 kDa, β chain). The deletion of LRP1 leads to embryonic lethality in mice, revealing a crucial but yet undefined role in embryogenesis and development. LRP1 has been postulated to participate in numerous diverse physiological and pathological processes ranging from plasma lipoprotein homeostasis, atherosclerosis, tumor evolution, and fibrinolysis to neuronal regeneration and survival. Many studies using cultured cells and animal models have revealed the important roles of LRP1 in vascular remodeling, foam cell biology, inflammation and atherosclerosis. However, its role in atherosclerosis remains controversial. LRP1 not only participates in the removal of atherogenic lipoproteins and proatherogenic ligands in the liver but also mediates the uptake of aggregated LDL to promote the formation of macrophage- and vascular smooth muscle cell (VSMC)-derived foam cells, which causes a prothrombotic transformation of the vascular wall. The dual and opposing roles of LRP1 may also represent an interesting target for atherosclerosis therapeutics. This review highlights the influence of LRP1 during atherosclerosis development, focusing on its dual role in vascular cells and immune cells.
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http://dx.doi.org/10.3389/fcvm.2021.682389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192809PMC
May 2021

Lipocalin 10 as a New Prognostic Biomarker in Sepsis-Induced Myocardial Dysfunction and Mortality: A Pilot Study.

Mediators Inflamm 2021 22;2021:6616270. Epub 2021 May 22.

Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Introduction: Sepsis-induced myocardial dysfunction (SIMD) is the most common complications of sepsis and septic shock with extremely high incidence and mortality. Lipocalin 10 (Lcn10) has recently been identified as a potential biomarker for heart failure, yet its relation to sepsis has not been investigated. The purpose of this study was to explore whether circulating Lcn10 could be used as a prognostic tool in patients with SIMD.

Methods: In this single-center observational pilot study, seventy-five sepsis patients were enrolled after sepsis diagnosis or ICU admission (45.3% female, median age 60 years), and 35 patients (46.7%) developed myocardial dysfunction. Serum Lcn10 levels of septic patients were measured using the enzyme-linked immunosorbent assay (ELISA) at the time of admission. Other biomarkers of cardiac function and Lcn10 concentration were compared between SIMD and non-SIMD groups.

Results: We observed that the median Lcn10 levels were 2.780 ng/mL in patients with SIMD and 2.075 ng/mL in patients without SIMD ( < 0.05). The area under the receiver operating characteristic (ROC) curve for the diagnosis of SIMD was 0.797 ( < 0.05). In addition, elevated serum Lcn10 levels at the time of admission were positively associated with 28-day mortality in septic patients.

Conclusions: Our study indicates that circulating Lcn10 levels may serve as a novel biomarker for the diagnosis and prognosis of myocardial dysfunction induced by sepsis. An additional large multicenter study may be warranted to confirm the findings of this study.
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http://dx.doi.org/10.1155/2021/6616270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166480PMC
May 2021

Calycosin-loaded nanoliposomes as potential nanoplatforms for treatment of diabetic nephropathy through regulation of mitochondrial respiratory function.

J Nanobiotechnology 2021 Jun 13;19(1):178. Epub 2021 Jun 13.

Department of Nephrology, The First Hospital Affiliated To Jinan University, NO.613, Huangpu Avenue West, Guangzhou, 510150, China.

Backgrounds: One of the most common complications in diabetic nephropathy is generation of high levels of ROS which can be regulated by herbal antioxidants. However, polyphenols like calycosin, the bioactive compound of Radix astragali suffer from low solubility and poor bioavailability.

Methods: Therefore, in the present study, calycosin-loaded nanoliposomes were fabricated and characterized by TEM, DLS and FTIR techniques. Afterwards, the drug loading (DL) and entrapment efficiency (EE), drug release, solubility, stability, and pharmacodynamic assays were performed. Finally, the antinephropathic effects of calycosin-loaded-nanoliposomes on mitochondria of kidney cells were explored by MTT, ROS, MDA, mitochondrial respiratory function assays.

Results: The result showed that the size, hydrodynamic radius, zeta potential, EE, and DL were, 80 nm, 133.99 ± 21.44 nm, - 20.53 ± 3.57, 88.37 ± 2.28%, and 7.48 ± 1.19%, respectively. The outcomes of in vitro release assay showed that calycosin-loaded nanoliposomes were significantly slow-release in dialysis media with pH 1.2, pH 6.9 and pH 7.4, at about 30 min, the dissolution of calycosin from nanoliposome became almost complete, and after 2 months, the calycosin-loaded nanoliposomes were still stable. Pharmacokinetic assay revealed that the AUC of calycosin in calycosin-loaded nanoliposome group was 927.39 ± 124.91 μg/L*h, which was 2.26 times than that of the free calycosin group (**P < 0.01). Additionally, the MRT and t of calycosin in the calycosin-loaded nanoliposome group were prolonged by 1.54 times and 1.33 times than that of free calycosin group, respectively (*P < 0.05). Finally, it was shown that calycosin-loaded nanoliposomes regulated the viability, ROS production, lipid peroxidation and function of mitochondria in kidney cells of diabetic rats as a model of diabetic nephropathy.

Conclusion: In conclusion it may be suggested that new therapies based on nano-formulated calycosin can restore mitochondrial function which can improve diabetic nephropathy.
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http://dx.doi.org/10.1186/s12951-021-00917-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201677PMC
June 2021
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