Publications by authors named "Xiaobo Wang"

531 Publications

Effects of azithromycin on treating chronic obstructive pulmonary disease with acute exacerbation of chronic bronchitis in the stable phase.

Am J Transl Res 2021 15;13(6):7370-7375. Epub 2021 Jun 15.

Department of Respiratory Medicine, The First People's Hospital of Fuyang Hangzhou Hangzhou 311400, Zhejiang 311400, China.

Objective: To explore the effects of azithromycinon in treatment of chronic obstructive pulmonary disease (COPD) in patients with acute exacerbation (AE) of chronic bronchitis (CB) in the stable phase.

Methods: Totally, 60 COPD patients with AE of CB were divided into control group (CG, 30 cases) and experimental group (EG, 30 cases) using the random number residue method. The CG was administered 250 mg salmeterol-fluticasone powder inhalation twice a day combined with 18 µg tiotropium bromide inhalation once a day. The EG was treated with 250 mg azithromycin tablets once a day in addition to the treatment of the CG. We compared the clinical effect, pulmonary function, and fractional exhaled nitric oxide index between two groups after treated for three-months.

Results: Compared with the CG, the EG showed a better clinical effect with a total effective rate at 86.67% after treatment (<0.05). The EG exhibited better FEV1 and FEV1% than the CG (<0.05). We also observed the difference between clinically FeNO-invalid patients before and after treatment was significant (<0.05). After treatment, this difference among groups was statistically significant (<0.05).

Conclusions: Azithromycin combined with salmeterol-fluticasone powder inhalation and tiotropium bromide inhalation have good effects for treating COPD patients with AE of CB in the stable stage and can improve the pulmonary function. When COPD with AE of CB was exacerbated, the FeNO index increased significantly, indicating a potential increase in the mucosal inflammatory cells and eosinophils of the airway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290734PMC
June 2021

Microbial Profiles of Retail Pacific Oysters () From Guangdong Province, China.

Front Microbiol 2021 7;12:689520. Epub 2021 Jul 7.

Department of Food Science, Foshan Polytechnic, Foshan, China.

Oysters are one of the main aquatic products sold in coastal areas worldwide and are popular among consumers because of their delicious taste and nutritional value. However, the microorganisms present in oysters may pose health risks to consumers. In this study, the microbial communities of Pacific oysters () collected from aquatic product markets in three cities (Guangzhou, Zhuhai, and Jiangmen) of Guangdong Province, China, where raw oysters are popular, were investigated. The plate counts of viable bacteria in oysters collected in the three cities were all approximately 2 log colony-forming units/g. High-throughput sequencing analysis of the V3-V4 region of the 16Sribosomal DNA gene showed a high level of microbial diversity in oysters, as evidenced by both alpha and beta diversity analysis. Proteobacteria, Bacteroidetes, and Firmicutes were the dominant phyla of the microorganisms present in these samples. A variety of pathogenic bacteria, including the fatal foodborne pathogen , were found, and was the dominant genus. Additionally, the relationship between other microbial species and pathogenic microorganisms may be mostly symbiotic in oysters. These data provide insights into the microbial communities of retail oysters in the Guangdong region and indicate a considerable risk related to the consumption of raw oysters.
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http://dx.doi.org/10.3389/fmicb.2021.689520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292972PMC
July 2021

Caveolin-1 promotes tumor cell proliferation and vasculogenic mimicry formation in human glioma.

Braz J Med Biol Res 2021 16;54(10):e10653. Epub 2021 Jul 16.

Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.
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http://dx.doi.org/10.1590/1414-431X2020e10653DOI Listing
July 2021

Different Effects of Total Bilirubin on 90-Day Mortality in Hospitalized Patients With Cirrhosis and Advanced Fibrosis: A Quantitative Analysis.

Front Med (Lausanne) 2021 23;8:704452. Epub 2021 Jun 23.

Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China.

Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.
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http://dx.doi.org/10.3389/fmed.2021.704452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260970PMC
June 2021

OmpC, a novel factor H-binding surface protein, is dispensable for the adherence and virulence of Salmonella enterica serovar Typhimurium.

Vet Microbiol 2021 Aug 18;259:109157. Epub 2021 Jun 18.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China; Key Laboratory of Animal Infectious Diseases, Ministry of Agriculture, Yangzhou University, China; Jiangsu Key Laboratory of Preventive Veterinary Medicine, Yangzhou University, China. Electronic address:

Salmonella enterica serovar Typhimurium utilizes a series of strategies to evade host innate immune defenses, including the serum complement system. Many microbial pathogens have evolved the ability to bind the complement regulatory protein factor H (FH) through their surface factor H-binding proteins (FHBPs) to circumvent the complement-mediated bactericidal effect. However, the roles of FHBPs in Salmonella pathogenesis are not well understood. In this study, we demonstrated that the survival of S. Typhimurium in human serum was decreased in a time and concentration dependent manner. Pre-incubation with FH attenuated the sensitivity of S. Typhimurium strain χ3761 to complement-mediated serum killing, suggesting FH binding enhance survival in serum. We aimed to identify novel S. Typhimurium FHBPs and characterize their biological functions. Here, six potential FHBPs were identified by two-dimensional (2D)-Far-western blot, and three of them were further confirmed to bind FH by Far-western blot and dot blot. We found that deletion of ompC (ΔompC) significantly inhibited the survival of S. Typhimurium strain χ3761 in human serum. Our results indicated that the ompC mutation does not affect χ3761 adhesion to HeLa cells. Furthermore, a mice infection model showed that deletion of ompC had no significant effect on the histopathological lesions or viability compared with the wild-type strain χ3761. In summary, these results suggested that OmpC is an important FHBP, but not a critical virulence factor of S. Typhimurium.
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http://dx.doi.org/10.1016/j.vetmic.2021.109157DOI Listing
August 2021

Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis.

Sci Transl Med 2021 06;13(599)

Department of Medicine, Columbia University, New York, NY 10032, USA.

Aberrant hepatocyte Notch activity is critical to the development of nonalcoholic steatohepatitis (NASH)-induced liver fibrosis, but mechanisms underlying Notch reactivation in developed liver are unclear. Here, we identified that increased expression of the Notch ligand Jagged1 () tracked with Notch activation and nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in human liver biopsy specimens and mouse NASH models. The increase in was mediated by hepatocyte Toll-like receptor 4 (TLR4)-nuclear factor κB (NF-κB) signaling in pericentral hepatocytes. Hepatocyte-specific overexpression exacerbated fibrosis in mice fed a high-fat diet or a NASH-provoking diet rich in palmitate, cholesterol, and sucrose and reversed the protection afforded by hepatocyte-specific TLR4 deletion, whereas hepatocyte-specific knockout mice were protected from NASH-induced liver fibrosis. To test therapeutic potential of this biology, we designed a -directed antisense oligonucleotide (ASO) and a hepatocyte-specific -acetylgalactosamine (GalNAc)-modified siRNA, both of which reduced NASH diet-induced liver fibrosis in mice. Overall, these data demonstrate that increased hepatocyte Jagged1 is the proximal hit for Notch-induced liver fibrosis in mice and suggest translational potential of Jagged1 inhibitors in patients with NASH.
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http://dx.doi.org/10.1126/scitranslmed.abe1692DOI Listing
June 2021

Imatinib reduces the fertility of male mice by penetrating the blood-testis barrier and inducing spermatogonia apoptosis.

Reprod Biol 2021 Jun 16;21(3):100527. Epub 2021 Jun 16.

Department of Hematology, The 967th Hospital of Chinese People's Liberation Army, Liaoning, China. Electronic address:

Imatinib, the first generation of tyrosine kinase inhibitor, is used to treat and improve the prognosis of chronic myelogenous leukemia (CML). Clinical data suggest that imatinib could cross the blood-testis barrier and reduces the fertility of patients with CML-chronic phase. However, its exact molecular mechanism has not been fully elucidated. In this study, adult male Kunming mice were treated with different doses of imatinib for 8 weeks. The fertility was evaluated, and the sex hormone levels in the blood were detected by enzyme-linked immunosorbent assay. Histological changes were detected by hematoxylin and eosin staining. The concentration of imatinib in semen and blood was detected by liquid chromatography-mass spectrometry. The ultrastructure of blood-testis barrier and apoptotic bodies were observed by transmission electron microscope. The expression of blood-testis barrier function-regulating protein, Mfsd2a, and apoptosis-associated proteins in testis tissue was detected by immunohistochemistry and Western blot. The results indicated that the fertility of male mice was significantly decreased in a dose-dependent manner after imatinib treatment. Certain hormones in the serum were increased in imatinib treatment groups. Sperm morphology and testicular tissue showed various changes after imatinib treatment. The blood-testis barrier was destroyed and the concentration of imatinib in semen was similar to that in blood after imatinib treatment. Apoptosis was significantly increased in testis tissue after imatinib treatment. Collectively, these results suggest that imatinib can alter blood-testis barrier function, induce apoptosis of spermatogonia, and adversely affect fertility by reducing the number of spermatozoa, decreasing sperm motility and increasing the deformity rate.
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http://dx.doi.org/10.1016/j.repbio.2021.100527DOI Listing
June 2021

The nearly complete genome of Ginkgo biloba illuminates gymnosperm evolution.

Nat Plants 2021 Jun 14;7(6):748-756. Epub 2021 Jun 14.

The Southern Modern Forestry Collaborative Innovation Center, the Key Lab of Tree Genetics and Biotechnology of Educational Department of China and the Key Lab of Tree Genetics and Silvicultural Sciences of Jiangsu Province, Nanjing Forestry University, Nanjing, China.

Gymnosperms are a unique lineage of plants that currently lack a high-quality reference genome due to their large genome size and high repetitive sequence content. Here, we report a nearly complete genome assembly for Ginkgo biloba with a genome size of 9.87 Gb, an N50 contig size of 1.58 Mb and an N50 scaffold size of 775 Mb. We were able to accurately annotate 27,832 protein-coding genes in total, superseding the inaccurate annotation of 41,840 genes in a previous draft genome assembly. We found that expansion of the G. biloba genome, accompanied by the notable extension of introns, was mainly caused by the insertion of long terminal repeats rather than the recent occurrence of whole-genome duplication events, in contrast to the findings of a previous report. We also identified candidate genes in the central pair, intraflagellar transport and dynein protein families that are associated with the formation of the spermatophore flagellum, which has been lost in all seed plants except ginkgo and cycads. The newly obtained Ginkgo genome provides new insights into the evolution of the gymnosperm genome.
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http://dx.doi.org/10.1038/s41477-021-00933-xDOI Listing
June 2021

8-Formylophiopogonanone B antagonizes doxorubicin-induced cardiotoxicity by suppressing heme oxygenase-1-dependent myocardial inflammation and fibrosis.

Biomed Pharmacother 2021 Aug 29;140:111779. Epub 2021 May 29.

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, No. 63, Wenhua Road, Shunqing District, Nanchong, Sichuan 637000, China; Academician Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China. Electronic address:

Doxorubicin (DOX) is a widely used antitumor drug that causes severe cardiotoxicity in patients; no effective strategy yet exists to address this problem. We previously reported that 8-formylophiopogonanone B (8-FOB), a natural isoflavone in Ophiopogon japonicas, antagonizes paraquat-induced hepatotoxicity. Here, we explored the mechanisms underlying DOX-induced cardiotoxicity as well as whether 8-FOB can alleviate DOX-induced cardiotoxicity. Acute cardiotoxicity was established by injecting C57BL/6J mice with a single dose of DOX (20 mg/kg, intraperitoneal). To elucidate the mechanisms underlying DOX-induced cardiotoxicity, differentially expressed genes between hearts from DOX-treated and control mice were identified from the Gene Expression Omnibus (GEO) database via GEO2R. Using the Cytoscape software plugin cytoHubba, five hub genes associated with DOX-induced cardiotoxicity were identified: CD68, PTEN, SERPINE1, AIF1, and HMOX1. However, of these, only HMOX1 protein expression levels were significantly increased after DOX treatment. We also confirmed that HMOX1-dependent myocardial inflammation and fibrosis were closely associated with DOX-induced cardiotoxicity. More importantly, 8-FOB protected against DOX-cardiotoxicity by ameliorating cardiac injury and dysfunction, reducing cardiac fibrosis and inflammatory cytokine release, and inhibiting HMOX1 expression. In conclusion, our results suggest that inhibition of HMOX1-dependent myocardial inflammatory insults and fibrosis is essential for 8-FOB to ameliorate DOX-caused cardiotoxicity.
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http://dx.doi.org/10.1016/j.biopha.2021.111779DOI Listing
August 2021

Ectopic expression of VRT-A2 underlies the origin of Triticum polonicum and Triticum petropavlovskyi with long outer glumes and grains.

Mol Plant 2021 May 25. Epub 2021 May 25.

State Key Laboratory for Agrobiotechnology and Key Laboratory of Crop Heterosis and Utilization (MOE) and Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing 100193, P. R. China. Electronic address:

Polish wheat (Triticum polonicum) is a unique tetraploid wheat species characterized by an elongated outer glume. The genetic control of the long-glume trait by a single semi-dominant locus, P1 (from Polish wheat), was established more than 100 years ago, but the underlying causal gene and molecular nature remain elusive. Here, we report the isolation of VRT-A2, encoding an SVP-clade MADS-box transcription factor, as the P1 candidate gene. Genetic evidence suggests that in T. polonicum, a naturally occurring sequence rearrangement in the intron-1 region of VRT-A2 leads to ectopic expression of VRT-A2 in floral organs where the long-glume phenotype appears. Interestingly, we found that the intron-1 region is a key ON/OFF molecular switch for VRT-A2 expression, not only because it recruits transcriptional repressors, but also because it confers intron-mediated transcriptional enhancement. Genotypic analyses using wheat accessions indicated that the P1 locus is likely derived from a single natural mutation in tetraploid wheat, which was subsequently inherited by hexaploid T. petropavlovskyi. Taken together, our findings highlight the promoter-proximal intron variation as a molecular basis for phenotypic differentiation, and thus species formation in Triticum plants.
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http://dx.doi.org/10.1016/j.molp.2021.05.021DOI Listing
May 2021

Tibetan Medicine Duoxuekang Capsule Ameliorates High-Altitude Polycythemia Accompanied by Brain Injury.

Front Pharmacol 2021 11;12:680636. Epub 2021 May 11.

State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Duoxuekang (DXK) capsule is an empirical prescription for Tibetan medicine in the treatment of hypobaric hypoxia (HH)-induced brain injury in the plateau. This study aimed to investigate the protective effects and underlying molecular mechanisms of DXK on HH-induced brain injury. UPLC-Q-TOF/MS was performed for chemical composition analysis of DXK. The anti-hypoxia and anti-fatigue effects of DXK were evaluated by the normobaric hypoxia test, sodium nitrite toxicosis test, and weight-loaded swimming test in mice. Simultaneously, SD rats were used for the chronic hypobaric hypoxia (CHH) test. RBC, HGB, HCT, and the whole blood viscosity were evaluated. The activities of SOD and MDA in the brain, and EPO and LDH levels in the kidney were detected using ELISA. H&E staining was employed to observe the pathological morphology in the hippocampus and cortex of rats. Furthermore, immunofluorescence and Western blot were carried out to detect the protein expressions of Mapk10, RASGRF1, RASA3, Ras, and IGF-IR in the brain of rats. Besides, BALB/c mice were used for acute hypobaric hypoxia (AHH) test, and Western blot was employed to detect the protein expression of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 in the cerebral cortex of mice. 23 different chemical compositions of DXK were identified by UPLC-Q-TOF/MS. The anti-hypoxia test verified that DXK can prolong the survival time of mice. The anti-fatigue test confirmed that DXK can prolong the swimming time of mice, decrease the level of LDH, and increase the hepatic glycogen level. Synchronously, DXK can decrease the levels of RBC, HGB, HCT, and the whole blood viscosity under the CHH condition. Besides, DXK can ameliorate CHH-induced brain injury, decrease the levels of EPO and LDH in the kidney, reduce MDA, and increase SOD in the hippocampus. Furthermore, DXK can converse HH-induced marked increase of Mapk10, RASGRF1, and RASA3, and decrease of Ras and IGF-IR. In addition, DXK can suppress the ratio of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 under the HH condition. Together, the cerebral protection elicited by DXK was due to the decrease of hematological index, suppressing EPO, by affecting the MAPK signaling pathway in oxidative damage, and regulating the RAS signaling pathway.
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http://dx.doi.org/10.3389/fphar.2021.680636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144525PMC
May 2021

A prognostic nomogram for long-term major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

BMC Cardiovasc Disord 2021 May 22;21(1):253. Epub 2021 May 22.

Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

Background: Accurate prediction of major adverse cardiovascular events (MACEs) is very important for the management of acute coronary syndrome (ACS) patients. We aimed to construct an effective prognostic nomogram for individualized risk estimates of MACEs for patients with ACS after percutaneous coronary intervention (PCI).

Methods: This was a prospective study of patients with ACS after PCI from January 2013 to July 2019 (n = 2465). After removing patients with incomplete clinical information, a total of 1986 patients were randomly divided into evaluation (n = 1324) and validation (n = 662) groups. Predictors included in the nomogram were determined by a multivariate Cox proportional hazards regression model based on the training set. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the discrimination and predictive accuracy of the nomogram, which were then compared with those of the classic models. The clinical utility of the nomogram was assessed by X-tile analysis and Kaplan-Meier curve analysis.

Results: Independent prognostic factors, including lactate level, age, left anterior descending branch stenosis, right coronary artery stenosis, brain natriuretic peptide level, and left ventricular ejection fraction, were determined and contained in the nomogram. The nomogram achieved good areas under the ROC curve of 0.712-0.762 in the training set and 0.724-0.818 in the validation set and well-fitted calibration curves. In addition, participants could be divided into two risk groups (low and high) according to this model.

Conclusions: A simple-to-use nomogram incorporating lactate level effectively predicted 6-month, 1-year, and 4-year MACE incidence among patients with ACS after PCI.
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http://dx.doi.org/10.1186/s12872-021-02051-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141252PMC
May 2021

Mutant TMEM230 induced neurodegeneration and impaired axonal mitochondrial transport.

Hum Mol Genet 2021 May 17. Epub 2021 May 17.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Parkinson's disease (PD) is a neurodegenerative disease with movement disorders including resting tremor, rigidity, bradykinesia, and postural instability. Recent studies have identified a new PD associated gene, TMEM230 (transmembrane protein 230). However, the pathological roles of TMEM230 and its variants are not fully understood. TMEM230 gene encodes two protein isoforms. Isoform2 is the major protein form (~95%) in human. In this study, we overexpress isoform2 TMEM230 variants (WT or PD-linked *184Wext*5 mutant) or knockdown endogenous protein in cultured SH-5Y5Y cells and mouse primary hippocampus neurons to study their pathological roles. We found that overexpression of WT and mutant TMEM230 or knockdown of endogenous TMEM230 induced neurodegeneration and impaired mitochondria transport at the retrograde direction in axons. Mutant TMEM230 caused more severe neurotoxicity and mitochondrial transport impairment than WT-TMEM230 did. Our results demonstrate that maintaining TMEM230 protein levels is critical for neuron survival and axon transport. These findings suggest that mutant-TMEM230-induced mitochondrial transport impairment could be the early event leading to neurite injury and neurodegeneration in PD development.
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http://dx.doi.org/10.1093/hmg/ddab128DOI Listing
May 2021

Malnutrition is associated with hyperinflammation and immunosuppression in COVID-19 patients: A prospective observational study.

Nutr Clin Pract 2021 May 12. Epub 2021 May 12.

Emergency Department, First Affiliated Hospital of Anhui Medical University, Hefei, PR, China.

Background: Coronavirus disease 2019 (COVID-19) is spreading globally and has caused many deaths. This study investigated, for the first time, COVID-19 patients' nutrition status and its effects on their inflammatory and immune responses.

Methods: Forty-seven COVID-19 patients were recruited for this prospective study. According to the subjective global assessment at admission, patients were divided into the normal nutrition (NN), risk of malnutrition (RMN), or MN group. Serum cytokines and whole blood T-cell subpopulations were measured to assess the inflammatory and immune responses in COVID-19 patients. Analysis of covariance and χ tests were used.

Results: On admission, the incidences of MN and the RMN in COVID-19 patients were 17.0% and 38.3%, respectively. The MN group had a higher proportion with severe/critical COVID-19 and a longer hospitalization duration than the NN group. Serum interleukin (IL) 6 concentrations were elevated in 97.9% of the patients and were the highest in malnourished patients. The IL-4 and IL-10 levels were elevated in 46.8% and 48.9% of the patients, respectively. The proportion of CD8+ T cells was significantly lower in the MN group than in the NN group.

Conclusion: A high proportion of COVID-19 patients are malnourished or at risk of malnuourishment, especially those with severe disease. MN is associated with hyperinflammation and immunosuppression in COVID-19 patients, and it may contribute to disease progression.
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http://dx.doi.org/10.1002/ncp.10679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242896PMC
May 2021

Amelioration of diabetic retinopathy in db/db mice by treatment with different proportional three active ingredients from Tibetan medicine Berberis dictyophylla F.

J Ethnopharmacol 2021 Aug 6;276:114190. Epub 2021 May 6.

Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Ethnopharmacological Relevance: Berberis dictyophylla F., a famous Tibetan medicine, has been used to prevent and treat diabetic retinopathy (DR) for thousands of years in clinic. However, its underlying mechanisms remain unclear.

Aim Of The Study: The present study was designed to probe the synergistic protection and involved mechanisms of berberine, magnoflorine and berbamine from Berberis dictyophylla F. on the spontaneous retinal damage of db/db mice.

Materials And Methods: The 14-week spontaneous model of DR in db/db mice were randomly divided into eight groups: model group, calcium dobesilate (CaDob, 0.23 g/kg) group and groups 1-6 (different proportional three active ingredients from Berberis dictyophylla F.). All mice were intragastrically administrated for a continuous 12 weeks. Body weight and fasting blood glucose (FBG) were recorded and measured. Hematoxylin-eosin and periodic acid-Schiff (PAS) stainings were employed to evaluate the pathological changes and abnormal angiogenesis of the retina. ELISA was performed to assess the levels of IL-6, HIF-1α and VEGF in the serum. Immunofluorescent staining was applied to detect the protein levels of CD31, VEGF, p-p38, p-JNK, p-ERK and NF-κB in retina. In addition, mRNA expression levels of VEGF, Bax and Bcl-2 in the retina were monitored by qRT-PCR analysis.

Results: Treatment with different proportional three active ingredients exerted no significant effect on the weight, but decreased the FBG, increased the number of retinal ganglionic cells and restored internal limiting membrane. The results of PAS staining demonstrated that the drug treatment decreased the ratio of endothelial cells to pericytes while thinned the basal membrane of retinal vessels. Moreover, these different proportional active ingredients can markedly downregulate the protein levels of retinal CD31 and VEGF, and serum HIF-1α and VEGF. The gene expression of retinal VEGF was also suppressed. The levels of retinal p-p38, p-JNK and p-ERK proteins were decreased by drug treatment. Finally, drug treatment reversed the proinflammatory factors of retinal NF-κB and serum IL-6, and proapoptotic Bax gene expression, while increased antiapoptotic Bcl-2 gene expression.

Conclusions: These results indicated that DR in db/db mice can be ameliorated by treatment with different proportional three active ingredients from Berberis dictyophylla F. The potential vascular protection mechanisms may be involved in inhibiting the phosphorylation of the MAPK signaling pathway, thus decreasing inflammatory and apoptotic events.
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http://dx.doi.org/10.1016/j.jep.2021.114190DOI Listing
August 2021

GmMs1 encodes a kinesin-like protein essential for male fertility in soybean (Glycine max L.).

J Integr Plant Biol 2021 Jun;63(6):1054-1064

The National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI)/Key Laboratory of Crop Gene Resource and Germplasm Enhancement (MOA), Institute of Crop Sciences, The Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

The application of heterosis is a promising approach for greatly increasing yield in soybean (Glycine max L.). Nuclear male sterility is essential for hybrid seed production and the utilization of heterosis. Here we report the cloning of the gene underlying the soybean male-sterile mutant ms-1, which has been widely used for recurrent selection in soybean breeding programs. We initially delimited the ms1 locus to a 16.15 kb region on chromosome 13, based on SLAF_BSA sequencing followed by genotyping of an F population segregating for the locus. Compared with the same region in fertile plants, the mutant region lacks a sequence of approximately 38.7 kb containing five protein-coding genes, including an ortholog of the kinesin-like protein gene NACK2, named GmMs1. The GmMs1 knockout plants generated via CRISPR/Cas-mediated gene editing displayed a complete male-sterile phenotype. Metabolic profiling showed that fertile anthers accumulated starch and sucrose normally, whereas sterile anthers had higher anthocyanin levels and lower flavonoid levels and lower antioxidant enzyme activities. These results provide insights into the molecular mechanisms governing male sterility and demonstrate that GmMs1 could be used to create male-sterile lines through targeted mutagenesis. These findings pave the way for designing seed production technology and an intelligent male-sterile line system to utilize heterosis in soybean.
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http://dx.doi.org/10.1111/jipb.13110DOI Listing
June 2021

The Underlying Molecular Mechanisms Involved in Traditional Chinese Medicine L. for the Treatment of Pelvic Inflammatory Disease.

Evid Based Complement Alternat Med 2021 8;2021:5552532. Epub 2021 Apr 8.

School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

L. (SCL) is extensively used in the treatment of pelvic inflammatory disease (PID). This study aimed to clarify the potential active ingredients of SCL and mechanisms on PID. SCL was widely distributed in Japan, South Korea, and China, which was traditionally considered heat-clearing, detoxicating, and dampness-eliminating medicine. Systems pharmacology revealed that 32 compounds in SCL may interact with 19 targets for immunoenhancement, antiapoptosis, anti-inflammation, and antioxidant activity of the PID model. Molecular docking revealed that isorhamnetin, moracin M, rutin, and oxyresveratrol may have higher binding potential with prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 1 (MAPK1), siderocalin (LCN2), tumor necrosis factor (TNF), and matrix metalloprotein-9 (MMP9), respectively. Molecular dynamics simulation showed that the binding modes of moracin M-MAPK1, rutin-TNF, and oxyresveratrol-MMP9 complexes were more stable, evidenced by relatively smaller fluctuations in root mean square deviation values. Conclusively, SCL may treat PID by inhibiting inflammatory factors, antitissue fibrosis, and microbial growth.
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http://dx.doi.org/10.1155/2021/5552532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052137PMC
April 2021

Exosome-delivered CD44v6/C1QBP complex drives pancreatic cancer liver metastasis by promoting fibrotic liver microenvironment.

Gut 2021 Apr 7. Epub 2021 Apr 7.

Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, China

Objective: Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Pro-oncogenic secretome delivery and trafficking via exosomes are crucial for pre-metastatic microenvironment formation and metastasis. This study aimed to explore the underlying mechanisms of how PDAC-derived exosomes (Pex) modulate the liver microenvironment and promote metastasis.

Design: C57BL/6 mice were 'educated' by tail vein Pex injection. The intrasplenic injection liver metastasis and PDAC orthotopic transplantation models were used to evaluate liver metastasis. Stable cell lines CD44v6 (CD44 variant isoform 6) or C1QBP (complement C1q binding protein) knockdown or overexpression was established using lentivirus transfection or gateway systems. A total of 142 patients with PDAC in Huashan Hospital were retrospectively enrolled. Prognosis and liver metastasis were predicted using Kaplan-Meier survival curves and logistic regression models.

Results: Pex tail vein injection induced the deposition of liver fibrotic extracellular matrix, which promoted PDAC liver metastasis. Specifically, the exosomal CD44v6/C1QBP complex was delivered to the plasma membrane of hepatic satellite cells (HSCs), leading to phosphorylation of insulin-like growth factor 1 signalling molecules, which resulted in HSC activation and liver fibrosis. Expression of Pex CD44v6 and C1QBP in PDAC patients with liver metastasis was significantly higher than in PDAC patients without liver metastasis, and simultaneous high expression of exosomal CD44v6 and C1QBP correlated with a worse prognosis and a higher risk of postoperative PDAC liver metastasis.

Conclusion: The Pex-derived CD44v6/C1QBP complex is essential for the formation of a fibrotic liver microenvironment and PDAC liver metastasis. Highly expressed exosomal CD44v6 and C1QBP are promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC.
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http://dx.doi.org/10.1136/gutjnl-2020-323014DOI Listing
April 2021

Prediction and analysis of multiple protein lysine modified sites based on conditional wasserstein generative adversarial networks.

BMC Bioinformatics 2021 Mar 31;22(1):171. Epub 2021 Mar 31.

Department of Information and Computer Science, University of Science and Technology Beijing, Beijing, 100083, China.

Background: Protein post-translational modification (PTM) is a key issue to investigate the mechanism of protein's function. With the rapid development of proteomics technology, a large amount of protein sequence data has been generated, which highlights the importance of the in-depth study and analysis of PTMs in proteins.

Method: We proposed a new multi-classification machine learning pipeline MultiLyGAN to identity seven types of lysine modified sites. Using eight different sequential and five structural construction methods, 1497 valid features were remained after the filtering by Pearson correlation coefficient. To solve the data imbalance problem, Conditional Generative Adversarial Network (CGAN) and Conditional Wasserstein Generative Adversarial Network (CWGAN), two influential deep generative methods were leveraged and compared to generate new samples for the types with fewer samples. Finally, random forest algorithm was utilized to predict seven categories.

Results: In the tenfold cross-validation, accuracy (Acc) and Matthews correlation coefficient (MCC) were 0.8589 and 0.8376, respectively. In the independent test, Acc and MCC were 0.8549 and 0.8330, respectively. The results indicated that CWGAN better solved the existing data imbalance and stabilized the training error. Alternatively, an accumulated feature importance analysis reported that CKSAAP, PWM and structural features were the three most important feature-encoding schemes. MultiLyGAN can be found at https://github.com/Lab-Xu/MultiLyGAN .

Conclusions: The CWGAN greatly improved the predictive performance in all experiments. Features derived from CKSAAP, PWM and structure schemes are the most informative and had the greatest contribution to the prediction of PTM.
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http://dx.doi.org/10.1186/s12859-021-04101-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010967PMC
March 2021

Improved receiver of ICI compensation for a spectral efficient frequency division multiplexing IM/DD system.

Opt Express 2021 Feb;29(3):3067-3080

Spectral efficient frequency division multiplexing (SEFDM) can greatly increase the spectral efficiency for intensity modulation/direct detection (IM/DD) optical communication systems. The sphere detection algorithm (SD) is the most efficient way to get the maximum likelihood (ML) solution to solve the inter-carrier interference (ICI) induced by the bandwidth compression of SEFDM system. However, SD algorithm is restricted by the numbers of subcarriers for SEFDM system, especially for larger numbers. Therefore, a sorted Gram-Schmidt (SGS) orthogonal decomposition algorithm, which can be applied to any subcarrier numbers, is proposed to overcome this restriction. To the best of our knowledge, the searched paths of FSD are researched for the first time to balance performance and complexity. Based on the analysis, a soft-tree-width sphere detection algorithm (SSD) is proposed and demonstrated by simulation and experiment. The results show that the proposed algorithm can greatly reduce the computational complexity (at least 40%) with the same system performance. The proposed algorithms are a promising candidate for flexible and efficient SEFDM systems. The SEFDM with the proposed detector is significant for the IM/DD optical systems.
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http://dx.doi.org/10.1364/OE.413161DOI Listing
February 2021

Morphology/Interstitial Fluid Pressure-Tunable Nanopomegranate Designed by Alteration of Membrane Fluidity under Tumor Enzyme and PEGylation.

Mol Pharm 2021 05 26;18(5):2039-2052. Epub 2021 Mar 26.

School of Pharmacy, China Pharmaceutical University, No. 639, Longmian Road, Nanjing 210009, PR China.

Up to now, insufficient drug accumulation in tumor remains a major challenge for nanochemotherapy. However, the spherical nanocarriers with large diameter, which are beneficial for blood circulation and tumor extravasation, cannot travel deep in a tumor. Additionally, high tumor interstitial fluid pressure (IFP) in the tumor microenvironment may promote the efflux of the penetrable nanodrugs. Therefore, the size and shape of nanocarriers as well as the tumoral IFP can be regulated synchronously for improved tumor penetration and combined chemotherapy. Herein, a novel dual-functional polymer-polypeptide (Biotin-PEG-GKGPRQITITK) for both verified tumor targeting and responsiveness was synthesized to construct the "peel" of nanopomegranate-like nanovectors (DI-MPL), in which docetaxel-loaded micelles was encapsulated as "seeds". Interestingly, DI-MPL was endowed multi-abilities of tunable size/shape switch and controlled release of IFP alleviator imatinib (IM), which were developed with one and the same strategy-alteration of membrane fluidity under the cleavage of polymer-polypeptide and PEGylation. As a result, the peel of DI-MPL could turn into small pieces with the seed scattered out in response to matrix metalloproteinase-9 (MMP-9), making nanopomegranate (180 nm) switch into spheres/disks (40 nm), during which IM is released to reduce IFP synchronously. With prominent tumor penetration ability in both multicellular tumor spheroids (MCTS) and tumor tissue, DI-MPL exhibited optimal inhibition of MCTS growth and the enhanced chemotherapy in comparison to other preparations. Meanwhile, the improved penetrability of DI-MPL in tumor tissue was found to be related to the reduced IFP, which is achieved via inhibiting expression of phosphorylated platelet-derived growth factor receptor-β (-PDGFR-β) by IM. Altogether, the bilateral adjusting strategies from nanocarrier size/shape and tumoral IFP with a single enzyme-responsive material could provide a potential combined chemotherapy to improve tumor penetration.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00036DOI Listing
May 2021

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment.

Purinergic Signal 2021 Jun 22;17(2):229-240. Epub 2021 Mar 22.

Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.
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http://dx.doi.org/10.1007/s11302-021-09774-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155138PMC
June 2021

JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells.

Biol Chem 2021 Jun 22;402(7):815-824. Epub 2020 Mar 22.

Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen518107, China.

Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of multiple tumors including acute myeloid leukemia cells (AML). Our present study found that the expression of histone lysine demethylase Jumonji domain containing-3 (JMJD3) was increased in AML cells as compared with that in human primary bone marrow (HPBM) cells. Knockdown of JMJD3 can decrease the proliferation of AML cells and increase the chemosensitivity of daunorubicin (DNR) and cytarabine (Ara-C). By screening the expression of cytokines involved in AML progression, we found that knockdown of JMJD3 can inhibit the expression of interleukin-6 (IL-6). Recombinant IL-6 (rIL-6) can attenuate si-JMJD3-suppressed proliferation of AML cells. Mechanistically, JMJD3 can positively regulate the promoter activity and transcription of IL-6 mRNA, while had no effect on its mRNA stability. Further, JMJD3 can regulate the expression of p65, which can directly bind with promoter of IL-6 to increase its transcription. Over expression of p65 significantly attenuated si-JMJD3-suppressed expression of IL-6. Collectively, we revealed that JMJD3 can regulate the proliferation and chemosensitivity of AML cells via upregulation of IL-6. It suggested that JMJD3 might be a potential therapy target for AML treatment.
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http://dx.doi.org/10.1515/hsz-2020-0345DOI Listing
June 2021

Cellular and Supracellular Planar Polarity: A Multiscale Cue to Elongate the Egg Chamber.

Front Cell Dev Biol 2021 2;9:645235. Epub 2021 Mar 2.

Molecular, Cellular and Developmental Biology Department (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, CNRS, UPS, Toulouse, France.

Tissue elongation is known to be controlled by oriented cell division, elongation, migration and rearrangement. While these cellular processes have been extensively studied, new emerging supracellular mechanisms driving tissue extension have recently been unveiled. Tissue rotation and actomyosin contractions have been shown to be key processes driving egg chamber elongation. First, egg chamber rotation facilitates the dorsal-ventral alignment of the extracellular matrix and of the cell basal actin fibers. Both fiber-like structures form supracellular networks constraining the egg growth in a polarized fashion thus working as 'molecular corsets'. Second, the supracellular actin fiber network, powered by myosin periodic oscillation, contracts anisotropically driving tissue extension along the egg anterior-posterior axis. During both processes, cellular and supracellular planar polarity provide a critical cue to control egg chamber elongation. Here we review how different planar polarized networks are built, maintained and function at both cellular and supracellular levels in the ovarian epithelium.
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http://dx.doi.org/10.3389/fcell.2021.645235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961075PMC
March 2021

Targeting SIRT1 to inhibit the proliferation of multiple myeloma cells.

Oncol Lett 2021 Apr 21;21(4):306. Epub 2021 Feb 21.

Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518107, P.R. China.

Multiple myeloma (MM) is the second most common hematopoietic malignancy and remains an incurable disease. Thus, novel drugs and therapeutic methods are required for patients with MM. The present study aimed to investigate the effect of sirtuin 1 (SIRT1) inhibitor cambinol on the proliferation and apoptosis of myeloma cell lines, RPMI8226 and U266. Moreover, the present study evaluated the underlying molecular mechanisms of proliferation inhibition and apoptosis induced by cambinol. A Cell Counting Kit-8 assay was used to measure the viability of RPMI8226 and U266 cells treated with cambinol. Apoptosis and the cell cycle were analyzed via flow cytometry. The expression levels of caspase-3, poly(ADP-ribose) polymerase 1 (PARP), p53, acetylated p53 (Ac-p53), Bcl-2, cyclin D1 and p21 were detected in cells treated with cambinol using western blot analysis. The results demonstrated that cambinol inhibited the proliferation of RPMI8226 and U266 cells in a time- and dose-dependent manner. Increased apoptosis and G cell cycle arrest, together with enhanced procaspase-3 degradation and PARP cleavage were identified in cambinol-treated cells compared with controls. Western blotting results also revealed the upregulation of p53 acetylation and p21, as well as the downregulation of Bcl-2 and cyclin D1 in cells treated with cambinol. In conclusion, the present results suggest that cambinol inhibits the proliferation and induces apoptosis in RPMI8226 and U266 cells by regulating acetylation of p53 via the targeting of SIRT1.
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http://dx.doi.org/10.3892/ol.2021.12567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905587PMC
April 2021

NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin.

Cell Death Discov 2021 Mar 15;7(1):50. Epub 2021 Mar 15.

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, 637000, Nanchong, P.R. China.

The exact mechanism of myocardial hypertrophy has not been completely elucidated. NOD-like receptor protein 3 (NLRP3) and the pyroptotic cascade play a critical role in cardiac hypertrophy and inflammation. The myokine irisin can inhibit NLRP3 activation, although its exact mechanism of action is unknown. In this study, we induced cardiac hypertrophy in a mouse model via aortic constriction (TAC) to further explore the pathological role of NLRP3 inflammasome-mediated pyroptosis and the potential therapeutic effects of irisin. Cardiac hypertrophy significantly increased the percentage of apoptotic cells and upregulated IL-1β, cleaved caspase-1, and GSDMD-N that lie downstream of the NLRP3 inflammasome. Subsequently, irisin was co-administered to the TAC mice or angiotensin II (Ang-II)-treated cardiomyocytes to observe whether it could attenuate pyroptosis and cardiac hypertrophy. We established a direct association between pyroptosis and cardiac hypertrophy and found that pharmacological or genetic inhibition of NLRP3 attenuated cardiac hypertrophy. Furthermore, ectopic overexpression of NLRP3 abrogated the cardioprotective effects of irisin. To summarize, pyroptosis is a pathological factor in cardiac hypertrophy, and irisin is a promising therapeutic agent that inhibits NLRP3-mediated pyroptosis of cardiomyocytes.
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http://dx.doi.org/10.1038/s41420-021-00434-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961005PMC
March 2021

Heterogeneous Diels-Alder tandem catalysis for converting cellulose and polyethylene into BTX.

J Hazard Mater 2021 07 19;414:125418. Epub 2021 Feb 19.

Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. Electronic address:

Producing biomass-derived aromatic hydrocarbons via controllable Diels-Alder reactions is a promising approach to recover energy and chemicals from waste streams. A tandem Diels-Alder catalysis consisting of SAPO-34 and Fe/HZSM-5 (stacked catalysis or mixed catalysis) was evaluated for thermochemical conversion of cellulose and polyethylene blends into benzene, toluene, and xylenes (BTX). Aromatization catalyst type significantly affected the activity of tandem catalysis, and the BTX obtained from the HZSM-5 stacked catalysis was ~2.3 times higher than that of the USY stacked one. An introduction of Fe active promoters into HZSM-5 increased the Lewis to Brønsted acid sites molar ratio (L/B) from 0.4 to 4.1. The comparison between Fe/HZSM-5 stacked catalysis and parent HZSM-5 single catalysis indicated that the former was more effective for BTX production, obtaining a nearly two-fold increase in yield with a high selectivity of 82.8%. A close proximity between Fe/HZSM-5 and SAPO-34 in the mixed catalysis increased the BTX enhancement to 1.8. A synergistic effect was provided by the coordination of Lewis and Brønsted acid sites in the Fe/HZSM-5 mixed catalysts for facilitating BTX generation, achieving a maximum of 25.9% at a Fe/HZSM-5 to SAPO-34 mass ratio of 1:1 with a theoretical L/B of 7.2. This work provides a sustainable strategy to produce biomass-derived aromatic hydrocarbons.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125418DOI Listing
July 2021

Hypoxia enhances the cytotoxic effect of AsS on rat ventricular H9c2 cells through activation of ubiquitin-proteasome system.

J Trace Elem Med Biol 2021 Jul 23;66:126720. Epub 2021 Jan 23.

Department of Pharmacy, The 967th hospital of People's Liberation Army, No.80, Shengli Road, Xigang, Dalian, Liaoning, 116021, China. Electronic address:

Background: AsS is widely used in Chinese traditional medicine compound. However, based on some recent studies, we found that the cardiotoxicity risk of using AsS in ischemic heart disease patients may be increased. To study this potential risk, we compared the effects of AsS on rat ventricular H9c2 cell line with or without hypoxic pretreatment, and to elucidate mechanisms of c-Cbl mediated ubiquitination/degradation of integrin β1.

Methods: The present study was conducted on rat ventricular H9c2 cell line in the absence or presence of hypoxic pretreatment for 6 h followed by AsS treatment for 24 h. Following AsS treatment, cell viability assay, flow cytometric quantification of apoptotic cells, caspase-3 activity assay and DAPI staining were conducted. Western blotting was carried out to detect expressions of ubiquitination related proteins. In addition, the ubiquitination/degradation of integrin β1 and the role of c-Cbl in it was evaluated by immunoprecipitation and immunoblot assay.

Results: The viability of cells with hypoxic pretreatment followed by AsS treatment was decreased significantly, apoptosis rate and the activity of caspase-3 were increased than AsS treatment alone. The ubiquitin-proteasome degradation pathway induced by AsS was further enhanced by hypoxic pretreatment. The results of IP and immunoblot assay showed hypoxic enhanced down-regulation effect of AsS on integrin β1 probably through c-Cbl activation.

Conclusions: This study demonstrated that the hypoxia enhanced cytotoxicity of AsS on H9c2 cells may through increasing the ubiquitin-proteasome degradation of integrin β1 mediated by the E3 ligase c-Cbl. The results provide an important clue that, in patients with ischemic heart disease, use of AsS may be associated with increased cardiotoxicity. We believe that the results worth to be further illuminated by in vivo and clinical research.
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http://dx.doi.org/10.1016/j.jtemb.2021.126720DOI Listing
July 2021

Spatial patterns and ecological drivers of soil nematode β-diversity in natural grasslands vary among vegetation types and trophic position.

J Anim Ecol 2021 05 17;90(5):1367-1378. Epub 2021 Mar 17.

Erguna Forest-Steppe Ecotone Research Station, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China.

Understanding biogeographic patterns of community assemblages is a core objective in ecology, but for soil communities these patterns are poorly understood. To understand the spatial patterns and underlying mechanisms of β-diversity in soil communities, we investigated the β-diversity of soil nematode communities along a 3,200-km transect across semi-arid and arid grasslands. Spatial turnover and nested-resultant are the two fundamental components of β-diversity, which have been attributed to various processes of community assembly. We calculated the spatial turnover and nested-resultant components of soil nematode β-diversity based on the β-partitioning framework. Distance matrices for the dissimilarity of soil nematode communities were computed using the 'Sørensen' method. We fitted negative exponential models to compare the distance decay patterns in nematode community similarity with geographic distance and plant community distance in three vegetation types (desert, desert steppe and typical steppe) and along the whole transect. Variation partitioning was used to distinguish the contribution of geographic distance and environmental variables to β-diversity and the partitioned components. Geographic distance and environmental filtering jointly drove the β-diversity patterns of nematode community, but environmental filtering explained more of the variation in β-diversity in the desert and typical steppe, whereas geographic distance was important in the desert steppe. Nematode community assembly was explained more by the spatial turnover component than by the nested-resultant component. For nematode feeding groups, the β-diversity in different vegetation types increased with geographic distance and plant community distance, but the nested-resultant component of bacterial feeders in the desert ecosystem decreased with geographic distance and plant community distance. Our findings show that spatial variation in soil nematode communities is regulated by environmental processes at the vegetation type scale, while spatial processes mainly work on the regional scale, and emphasize that the spatial patterns and drivers of nematode β-diversity differ among trophic levels. Our study provides insight into the ecological processes that maintain soil biodiversity and biogeographic patterns of soil community assemblage at large spatial scales.
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http://dx.doi.org/10.1111/1365-2656.13461DOI Listing
May 2021

Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis.

J Clin Invest 2021 Apr;131(8)

Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

Efferocytosis, the process through which apoptotic cells (ACs) are cleared through actin-mediated engulfment by macrophages, prevents secondary necrosis, suppresses inflammation, and promotes resolution. Impaired efferocytosis drives the formation of clinically dangerous necrotic atherosclerotic plaques, the underlying etiology of coronary artery disease (CAD). An intron of the gene encoding PHACTR1 contains rs9349379 (A>G), a common variant associated with CAD. As PHACTR1 is an actin-binding protein, we reasoned that if the rs9349379 risk allele G causes lower PHACTR1 expression in macrophages, it might link the risk allele to CAD via impaired efferocytosis. We show here that rs9349379-G/G was associated with lower levels of PHACTR1 and impaired efferocytosis in human monocyte-derived macrophages and human atherosclerotic lesional macrophages compared with rs9349379-A/A. Silencing PHACTR1 in human and mouse macrophages compromised AC engulfment, and Western diet-fed Ldlr-/- mice in which hematopoietic Phactr1 was genetically targeted showed impaired lesional efferocytosis, increased plaque necrosis, and thinner fibrous caps - all signs of vulnerable plaques in humans. Mechanistically, PHACTR1 prevented dephosphorylation of myosin light chain (MLC), which was necessary for AC engulfment. In summary, rs9349379-G lowered PHACTR1, which, by lowering phospho-MLC, compromised efferocytosis. Thus, rs9349379-G may contribute to CAD risk, at least in part, by impairing atherosclerotic lesional macrophage efferocytosis.
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http://dx.doi.org/10.1172/JCI145275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262505PMC
April 2021
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