Publications by authors named "Yuanyuan Wang"

1,470 Publications

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Comprehensive analyses reveal TKI-induced remodeling of the tumor immune microenvironment in EGFR/ALK-positive non-small-cell lung cancer.

Oncoimmunology 2021 16;10(1):1951019. Epub 2021 Jul 16.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Tyrosine kinase inhibitors (TKI) play a pivotal role in the treatment of non-small-cell lung cancer (NSCLC) with mutations in epidermal growth factor receptor (EGFR) and rearrangements in anaplastic lymphoma kinase (ALK). However, the influences of TKIs on the tumor immune microenvironment (TIM), especially dynamic changes of responders, have not yet been fully elucidated. Therefore, RNA sequencing and whole-exome sequencing were performed on EGFR/ALK-positive NSCLC samples before and after TKI treatment. In combination with neoantigen and mutational-load estimations, xCell and single-sample gene set enrichment analysis (ssGSEA) were used to assess tumor immune-cell infiltration and activity. Furthermore, weighted-gene correlation network analysis and the bottleneck method were used to identify the hub genes that affected treatment-related immune responses. We found that TKI treatment remodeled the TIM in treatment-responsive samples. Profound increases in the rate of anti-tumor cell infiltration and cytotoxicity was observed following TKI treatment, while antigen presentation was limited in ALK-rearranged samples. However, no significant change in anti-tumor cell infiltration or cytotoxicity was found between pre-treatment and post-progression samples. Subsequently, we found that neurofilament heavy (NEFH) mutations were enriched in samples after TKI treatment and were associated with reduced neutrophil infiltration. The cytotoxicity of EGFR-mutant NSCLCs with co-driver TP53 mutation and ALK-rearranged samples with wild-type TP53 seems to be more easily induced by TKI. Finally, the immune-associated score generated by hub genes was positively correlated with immune infiltration, immune activation, and a favorable prognosis. In conclusion, the dynamic changes in the TIM provide clues to drug selection and timing for TKI-immunotherapy combinations.
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http://dx.doi.org/10.1080/2162402X.2021.1951019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288040PMC
July 2021

YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis.

Pathobiology 2021 Aug 3:1-12. Epub 2021 Aug 3.

Department of Pathophysiology, Guizhou Medical University, Guiyang, China.

Objective: The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis.

Methods: C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson's trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman's analysis.

Results: Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury.

Conclusion: YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.
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http://dx.doi.org/10.1159/000517575DOI Listing
August 2021

Aucuboside Inhibits the Generation of Th17 Cells in Mice Colitis.

Front Pharmacol 2021 16;12:696599. Epub 2021 Jul 16.

Department of Anesthesiology, The Fourth Affiliated Hospital, China Medical University, Shenyang, China.

Aucuboside is an iridoid glycoside extracted from traditional Chinese medicine such as , possessing a wide range of biological activities, including antioxidant, anti-aging, anti-inflammatory, and anti-fibrotic effects. The effects of aucuboside on inflammatory bowel disease (IBD) have not been studied. Therefore, the effects of aucuboside on the generation of Foxp3+ regulatory T (Treg) cells and IL-17-producing T helper (Th17) cells in colitis were studied. A mouse colitis model was established by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to mimic human IBD. The generation of Treg and Th17 cells was evaluated by flow cytometry. Aucuboside significantly alleviated colitis symptoms, including weight loss, high disease activity index, and inflammatory responses. The generation of Th17 cells in colitis was significantly inhibited by aucuboside and accompanied by the suppression of IL-17 expression. In Raw264.7 cells, the LPS-induced increase in IL-17 expression was also suppressed by aucuboside, which was significantly blocked by the RORγt inhibitor sr2211. In addition, the decrease in the proportion of Treg cells was also partially reversed by aucuboside, which may reflect the aucuboside-induced inhibition of Th17 cells. This previously unrecognized immunoregulatory function of aucuboside may have clinical applications in IBD.
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http://dx.doi.org/10.3389/fphar.2021.696599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322701PMC
July 2021

CD30L classical monocytes play a pro-inflammatory role in the development of ulcerative colitis in patients.

Mol Immunol 2021 Jul 28;138:10-19. Epub 2021 Jul 28.

Department of Immunology, China Medical University, 110122, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. Electronic address:

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease that affects the large intestine and exhibits a relapsing and remitting course. It is a complex immune-mediated disease of the gastrointestinal tract that increases morbidity and negatively influences the quality of life. Although our previous studies have indicated that CD30L is involved in the adaptive immune response in UC, it remains unclear whether it participates in the innate immune response. Our results revealed that the CD30L level significantly increased in the circulating classical monocytes of patients with UC and showed a positive correlation with the severity of UC. CD30L may participate in monocyte-mediated inflammation in patients with UC through the activation of circulating classical monocytes. The present study provides insights into a marker of severity and a potential target for the development of immunological therapy of UC.
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http://dx.doi.org/10.1016/j.molimm.2021.06.016DOI Listing
July 2021

Differences in Retinal and Choroidal Vasculature and Perfusion Related to Axial Length in Pediatric Anisomyopes.

Invest Ophthalmol Vis Sci 2021 Jul;62(9):40

Eye Hospital and School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: The purpose of this study was to evaluate the interocular differences in choroidal vasculature, choriocapillaris perfusion, and retinal microvascular network, and to explore their associations with interocular asymmetry in axial lengths (ALs) in children with anisomyopia.

Methods: Refractive error, AL, and other biometric parameters were measured in 70 children with anisomyopia. Using optical coherence tomography (OCT) and OCT-angiography, we measured the submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow deficit (CcFD), retinal vessel density (VD), and foveal avascular zone (FAZ) area.

Results: The mean interocular differences in spherical equivalent refraction and AL were -2.26 ± 0.94 diopters and 0.95 ± 0.46 mm, respectively. Submacular ChT, TCA, LA, SA, and CVI were all significantly lower in the more myopic (longer AL) eyes than in the less myopic (shorter AL) fellow eyes. In eyes with longer ALs, both the CcFD and FAZ areas were significantly greater, whereas the superficial and deep retinal VDs were significantly less. After adjusting for corneal power and intraocular pressure, interocular differences in LA (β = -0.774), SA (β = -0.991), and CcFD (β = 0.040) were significantly associated with interocular asymmetry in AL (all P < 0.05).

Conclusions: In pediatric anisomyopes, eyes with longer ALs tended to have lower choroidal vascularity and choriocapillaris perfusion than the contralateral eyes with shorter ALs. Longitudinal investigations would be useful follow-ups to test for a causal role of choroidal circulation in human myopia.
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http://dx.doi.org/10.1167/iovs.62.9.40DOI Listing
July 2021

Genetic characterisation for Yan'an Han population in Northern Shaanxi Province, China, via 38Y-STRs using Yfiler™ Platinum.

Ann Hum Biol 2021 Jul 26:1-8. Epub 2021 Jul 26.

Key Laboratory of Cell Engineering in Guizhou Province, Affiliated Hospital of Zunyi Medical University, Guizhou, China.

Background: Haplotype/allele frequency data of Y-chromosomal STR loci in ethnically diverse populations are essential for forensics, anthropology and genealogy. However, genetic structure and forensic characterisation of the Chinese Han population residing in Yan'an, in the Northern Shaanxi Province, remain unclear.

Aim: To assess forensic efficiency for 38 Y-Chromosomal STR loci in Yan'an Han population and reveal the population genetic relationships between Yan'an Han and other populations at a nationwide and worldwide level.

Subjects And Methods: 719 healthy unrelated males were genotyped using the Yfiler™ Platinum system. Haplotype/allele frequencies and forensic parameters were calculated. Multi-dimensional scaling plots (MDS) and neighbor-joining (N-J) tree were used to explore the population structure based on the pairwise gene distances (Rst).

Results: A total of 707 haplotypes were identified, among which 697 unique haplotypes were observed (98.59%). The overall haplotype diversity (HD) and discrimination capacity (DC) were 0.9999 and 0.9833, respectively. Comprehensive population comparisons showed Yan'an Han is genetically closer to linguistically similar populations in China, and more related to East Asian populations around the world.

Conclusion: The present results give a unique insight into the Yan'an Han population via the set of 38 Y-STRs, which can be used for forensic practice and human genetics research.
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http://dx.doi.org/10.1080/03014460.2021.1951350DOI Listing
July 2021

The effects of CPET-guided cardiac rehabilitation on the cardiopulmonary function, the exercise endurance, and the NT-proBNP and hscTnT levels in CHF patients.

Am J Transl Res 2021 15;13(6):7104-7114. Epub 2021 Jun 15.

Cardiac Rehabilitation Center, Rizhao International Heart Hospital Rizhao, Shandong Province, China.

Objective: To explore the effects of cardiopulmonary exercise testing (CPET) on the cardiopulmonary function, the exercise endurance, and the NT-proBNP and hscTnT levels in chronic heart failure (CHF) patients.

Methods: Altogether 98 patients with CHF were randomly divided into a control group and a CPET group, with 49 cases in each group. The control group was administered routine treatment, and the CPET group was administered CPET cardiac rehabilitation training in addition to the routine treatment. Heart and lung function, exercise endurance, and the peripheral blood NTproBNP, hscTnT, and CRP levels were observed. The patients' quality of life, anxiety, and depression were observed using the scale.

Results: After the treatment, the left ventricular end systolic diameters (LVESD) and the left ventricular end diastolic diameters (LVEDD) were significantly decreased, the left ventricular ejection fractions (LVEF), the stroke volumes (SV), and the CI levels were significantly increased, and there were significant differences in these indexes between the CPET group and the control group (all P<0.05). After the treatment, the carbon dioxide ventilation equivalent slope (VE/VCOslop) decreased significantly, the peak oxygen consumption (peakVO) and anaerobic threshold oxygen consumption (VOAT) levels increased significantly, and there were significant differences in these indicators between the CPET group and the control group (all P<0.05). Compared with the control group, the exercise endurance, the maximum oxygen uptake capacity (VOmax), the maximum power, the exhaustion times, and the six-minute walking test (6MWT) levels in the CPET group increased significantly (all P<0.05). After the treatment, the N-terminal precursor brain natriuretic peptide (NTproBNP), the high sensitivity cardiac troponin (hscTnT), and the C-reactive protein (CRP) levels in the two groups were decreased compared with their pre-treatment levels, and there were significant differences in these indexes between the CPET group and the control group (all P<0.05). After the treatment, the Minnesota living with heart failure questionnaire (MLHFQ), the self-rating anxiety scale (SAS), and the self-rating depression scale (SDS) scores in the two groups were significantly lower than they were before the treatment, and there were significant differences in the two scores between the CPET group and the control group (all P<0.05).

Conclusion: CPET for patients with CHF helps increase heart and lung function, improves exercise endurance, reduces the NT-proBNP and hscTnT levels, and improves patients' quality of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290646PMC
June 2021

The Association Between Different Trajectories of Low Back Pain and Degenerative Imaging Findings in Young Adult Participants within The Raine Study.

Spine (Phila Pa 1976) 2021 Jul 16. Epub 2021 Jul 16.

School of Physiotherapy and Exercise Science, Curtin University, Perth, Australia Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia Envision Medical Imaging, Perth, Australia Fiona Stanley Hospital, Perth, Australia School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia Envision Medical Imaging, Perth, Australia Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Rehabilitation Services of South Karelia Social and Health Care District, Lappeenranta, Finland Department of Orthopaedic Surgery, RUSH University, USA Amsterdam UMC, Vrije Universiteit, Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands Center for Muscle and Joint Health, University of Southern Denmark, Odense, Denmark.

Study Design: case-control study.

Objective: Investigate the association between lumbar spine MRI findings and 5-year trajectories of low back pain (LBP) in young Australian adults.

Summary Of Background Data: The association between lumbar spine imaging findings and LBP remains unclear due to important limitations of previous research, such as a lack of clearly defined LBP phenotypes and inadequate controlling for age, which may substantially affect the association.

Methods: Seventy-eight 'case' participants with a previously identified 'consistent high disabling LBP' trajectory from age 17 to 22 years and 78 'control' participants from a trajectory with consistently low LBP over the same time period, matched for sex, body mass index, physical activity levels and work physical demands, were identified from Gen2 Raine Study participants. At age 27, participants underwent a standardised lumbar MRI scan, from which specific MRI phenotypes were identified. Primary analyses used unconditional logistic regression, adjusting for covariates used in the matching process, to investigate the relationship between presence of each imaging finding and being a case or control. Secondary analyses explored those relationships based on the number of spinal levels with each MRI finding.

Results: The odds for being a case compared to a control were higher in those with disc degeneration (Pfirrmann grade ≥ 3; OR = 3.21, 95%CI:1.60-6.44; p = 0.001) or those with a herniation (OR = 1.90, 95%CI:0.96-3.74; p = .065). We also found that the association became substantially stronger when either disc degeneration or herniation was present at 2 or more spinal levels (OR = 5.56, 95%CI:1.97-15.70; p = 0.001, and OR = 5.85, 95%CI:1.54-22.25; p = .009, respectively). The other investigated MRI findings were not associated with greater odds of being a case.

Conclusion: Lumbar disc degeneration and herniation may be important contributors to disabling LBP in young adults. Further investigation of their potential prognostic and causal roles is indicated.Level of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000004171DOI Listing
July 2021

Binding sites, vibrations and spin-lattice relaxation times in europium(II)-based metallofullerene spin qubits.

Chemistry 2021 Jul 15. Epub 2021 Jul 15.

University of Valencia: Universitat de Valencia, Instituto de Ciencia Molecular, SPAIN.

To design molecular spin qubits with enhanced quantum coherence, a control of the coupling between the local vibrations and the spin states is crucial, which could be realized in principle by engineering molecular structures via coordination chemistry. To this end, understanding the underlying structural factors that govern the spin relaxation is a central topic. Here, we report the investigation of the spin dynamics in a series of chemically-designed europium(II)-based endohedral metallofullerenes (EMFs). By introducing a unique structural difference, i.e. metal-cage binding site, while keeping other molecular parameters constant between different complexes, these manifest the key role of the three low energy metal-based vibrations in mediating the spin-lattice relaxation times ( T 1 ). The temperature dependence of T 1 can thus be normalized by the frequencies of these low energy vibrations to show an unprecedentedly universal behavior for EMFs in frozen CS 2 solution. Our theoretical analysis indicates that this structural difference determines not only the vibrational rigidity but also spin-vibration coupling in these EMF-based qubit candidates.
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http://dx.doi.org/10.1002/chem.202101922DOI Listing
July 2021

Radiogenomic Analysis of Papillary Thyroid Carcinoma for Prediction of Cervical Lymph Node Metastasis: A Preliminary Study.

Front Oncol 2021 29;11:682998. Epub 2021 Jun 29.

Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Papillary thyroid carcinoma (PTC) is characterized by frequent metastases to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound, and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumors.

Methods: In total, 270 patients were enrolled in this prospective study, and radiomic features were extracted according to multiple guidelines. A radiomic signature was built with selected features in the training cohort and validated in the validation cohort. The total protein extracted from tumor samples was analyzed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Genes in modules related to metastasis were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was built to identify the hub genes in the modules. Finally, the screened hub genes were validated by immunohistochemistry analysis.

Results: The radiomic signature showed good performance for predicting CLN status in training and validation cohorts, with area under curve of 0.873 and 0.831 respectively. A radiogenomic map was created with nine significant correlations between radiomic features and gene modules, and two of them had higher correlation coefficient. Among these, MEmeganta representing the upregulation of telomere maintenance telomerase and cell-cell adhesion was correlated with 'Rectlike' and 'deviation ratio of tumor tissue and normal thyroid gland' which reflect the margin and the internal echogenicity of the tumor, respectively. MEblue capturing cell-cell adhesion and glycolysis was associated with feature 'minimum calcification area' which measures the punctate calcification. The hub genes of the two modules were identified by protein-protein interaction network. Immunohistochemistry validated that LAMC1 and THBS1 were differently expressed in metastatic and non-metastatic tissues (p=0.003; p=0.002). And LAMC1 was associated with feature 'Rectlike' and 'deviation ratio of tumor and normal thyroid gland' (p<0.001; p<0.001); THBS1 was correlated with 'minimum calcification area' (p<0.001).

Conclusions: The radiomic signature proposed here has the potential to noninvasively predict the CLN status in PTC patients. Merging imaging phenotypes with genomic data could allow noninvasive identification of the molecular properties of PTC tumors, which might support clinical decision making and personalized management.
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http://dx.doi.org/10.3389/fonc.2021.682998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276635PMC
June 2021

Identification of evodiamine and rutecarpine as novel TMEM16A inhibitors and their inhibitory effects on peristalsis in isolated Guinea-pig ileum.

Eur J Pharmacol 2021 Jul 12;908:174340. Epub 2021 Jul 12.

Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, China; Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Hebei University of Chinese Medicine, Shijiazhuang, China. Electronic address:

The transmembrane member 16A (TMEM16A)-encoded Ca-activated Cl channel (CaCC) is expressed in interstitial cells of Cajal (ICCs) and involved in the generation of the slow-wave currents of gastrointestinal (GI) smooth muscles. TMEM16A modulators have been shown to positively or negatively regulate the contraction of gastrointestinal smooth muscle. Therefore, targeting the pharmacological modulation of TMEM16A may represent a novel treatment approach for gastrointestinal dysfunctions such as constipation and diarrhoea. In this study, evodiamine and rutecarpine were extracted from the traditional Chinese medicine Evodia rutaecarpa and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on intestinal peristalsis were examined. Whole-cell patch clamp results show that evodiamine and rutecarpine inhibited TMEM16A Cl currents in CHO cells. The half-maximal inhibition values (IC) of evodiamine and rutecarpine on TMEM16A Cl currents were 11.8 ± 1.3 μΜ and 9.2 ± 0.4 μM, and the maximal effect values (E) were 95.8 ± 5.1% and 99.1 ± 1.6%, respectively. The Lys, Thr, and Met in TMEM16A are critical for evodiamine and rutecarpine's inhibitory effects. Further functional studies show that both evodiamine and rutecarpine can significantly suppress the peristalsis in isolated guinea-pig ileum. These findings demonstrate that evodiamine and rutecarpine are new TMEM16A inhibitors and support the regulation effect of TMEM16A modulators on gastrointestinal motility.
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http://dx.doi.org/10.1016/j.ejphar.2021.174340DOI Listing
July 2021

Author Correction: Deep learning radiomics can predict axillary lymph node status in early-stage breast cancer.

Nat Commun 2021 Jul 12;12(1):4370. Epub 2021 Jul 12.

Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

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http://dx.doi.org/10.1038/s41467-021-24605-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275735PMC
July 2021

Metabolomic analysis of untargeted bovine uterine secretions in dairy cows with endometritis using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

Res Vet Sci 2021 Jul 7;139:51-58. Epub 2021 Jul 7.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China. Electronic address:

Endometritis is among the most common bovine uterine diseases; as a cause of infertility, it affects the progress of the cattle industry. In this study, we used a novel technique based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for comparative metabolomics of uterine secretions in healthy cows and cows with endometritis, classified based on clinical symptoms. Univariate and multivariate statistical analyses revealed significant differences between the two groups (n = 12). Compared with healthy uterine secretion samples, in the clinical endometritis samples, coumaric acid, benzoic acid, and equol were downregulated. However, l-phenylalanine, glutamine, succinic acid, linoleate, arachidonic acid, and other metabolites were upregulated, revealing variations between healthy cows and cows with endometritis (p < 0.05). This metabolomic approach may provide an in-depth understanding of endometritis pathobiology, along with a theoretical framework for the diagnosis and treatment of this bovine disease.
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http://dx.doi.org/10.1016/j.rvsc.2021.07.006DOI Listing
July 2021

Recognition of lipoproteins by scavenger receptor class A members.

J Biol Chem 2021 Jul 9:100948. Epub 2021 Jul 9.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai; University of Chinese Academy of Sciences, Beijing, China; Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; Shanghai Key Laboratory of Biliary Tract Disease, Shanghai, China. Electronic address:

Scavenger receptor class A (SR-A) proteins are type II transmembrane glycoproteins that form homotrimers on the cell surface. This family has five known members (SCARA1 to 5, or SR-A1 to A5) that recognize a variety of ligands and are involved in multiple biological pathways. Previous reports have shown that some SR-A family members can bind modified low-density lipoproteins (LDL); however, the mechanisms of the interactions between the SR-A members and these lipoproteins are not fully understood. Here we systematically characterize the recognition of SR-A receptors with lipoproteins and report that SCARA1 (SR-A1, CD204), MARCO (SCARA2), and SCARA5 recognize acetylated or oxidized LDL and very low-density lipoproteins (VLDL) in a Ca-dependent manner through their C-terminal scavenger receptor cysteine-rich (SRCR) domains. These interactions occur specifically between the SRCR domains and the modified apoB component of the lipoproteins, suggesting that they might share a similar mechanism for lipoprotein recognition. Meanwhile, SCARA4, a SR-A member with a carbohydrate recognition domain instead of the SRCR domain at the C-terminus, shows low affinity for modified LDL and VLDL, but binds in a Ca-independent manner. SCARA3, which does not have a globular domain at the C-terminus, was found to have no detectable binding with these lipoproteins. Taken together, these results provide mechanistic insights into the interactions between SR-A family members and lipoproteins that may help us to understand the roles of SR-A receptors in lipid transport and related diseases such as atherosclerosis.
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http://dx.doi.org/10.1016/j.jbc.2021.100948DOI Listing
July 2021

Enhanced Electrochemical HO Production via Two-Electron Oxygen Reduction Enabled by Surface-Derived Amorphous Oxygen-Deficient TiO.

ACS Appl Mater Interfaces 2021 Jul 12;13(28):33182-33187. Epub 2021 Jul 12.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China.

The electrochemical oxygen reduction reaction (ORR) is regarded as an attractive alternative to the anthraquinone process for sustainable and on-site hydrogen peroxide (HO) production. It is however hindered by low selectivity due to strong competition from the four-electron ORR and needs efficient catalysts to drive the 2e ORR. Here, an acid oxidation strategy is proposed as an effective strategy to boost the 2e ORR activity of metallic TiC via in-site generation of a surface amorphous oxygen-deficient TiO layer. The resulting a-TiO/TiC exhibits a low overpotential and high HO selectivity (94.1% at 0.5 V vs reversible hydrogen electrode (RHE)), and it also demonstrates robust stability with a remarkable productivity of 7.19 mol g h at 0.30 V vs RHE. The electrocatalytic mechanism of a-TiO/TiC is further revealed by density functional theory calculations.
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http://dx.doi.org/10.1021/acsami.1c09871DOI Listing
July 2021

Enhanced Electrochemical HO Production via Two-Electron Oxygen Reduction Enabled by Surface-Derived Amorphous Oxygen-Deficient TiO.

ACS Appl Mater Interfaces 2021 Jul 12;13(28):33182-33187. Epub 2021 Jul 12.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China.

The electrochemical oxygen reduction reaction (ORR) is regarded as an attractive alternative to the anthraquinone process for sustainable and on-site hydrogen peroxide (HO) production. It is however hindered by low selectivity due to strong competition from the four-electron ORR and needs efficient catalysts to drive the 2e ORR. Here, an acid oxidation strategy is proposed as an effective strategy to boost the 2e ORR activity of metallic TiC via in-site generation of a surface amorphous oxygen-deficient TiO layer. The resulting a-TiO/TiC exhibits a low overpotential and high HO selectivity (94.1% at 0.5 V vs reversible hydrogen electrode (RHE)), and it also demonstrates robust stability with a remarkable productivity of 7.19 mol g h at 0.30 V vs RHE. The electrocatalytic mechanism of a-TiO/TiC is further revealed by density functional theory calculations.
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http://dx.doi.org/10.1021/acsami.1c09871DOI Listing
July 2021

Validation of the Chinese Version of the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults.

J Sex Med 2021 Jul 8. Epub 2021 Jul 8.

Vanke School of Public Health, Tsinghua University, Beijing, China. Electronic address:

Background: The number of individuals with potential gender dysphoria (GD) being referred to specialized gender identity clinics or programs is increasing internationally; these cases are initially screened using the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA).

Aim: The current study aimed to assess the psychometric properties of the GIDYQ-AA in a sample of adolescents and young adults from China.

Methods: A cross-sectional study was conducted in October 2020. Sociodemographic information of the participants was first collected. Participants then completed the GIDYQ-AA, the Generalized Anxiety Disorder-7 scale, the Patient Health Questionnaire-9, and a suicidal ideation assessment. A total of 2,533 participants with a mean age of 19.30 (SD = 1.19) years were recruited. Of the participants, 841 (33.2%) were cis men, 1,589 (62.7%) were cis women, 66 (2.6%) self-identified as transgender, 17 (0.7%) self-identified as non-binary, and 20 (0.8%) self-identified as gender queer.

Results: The GIDYQ-AA had high internal consistency with a Cronbach's alpha = 0.89. Exploratory factor analysis showed that the GIDYQ-AA had a four-factor structure in China. The GIDYQ-AA was significantly correlated with anxiety symptoms (r = -0.32, P < .01), depressive symptoms (r = -0.33, P < .01), and suicidal ideation (r = -0.20, P < .01).

Clinical Translation: The Chinese version of GIDYQ-AA is a useful measurement with high practical value, which could promote the assessment and research of GD across China or among Chinese migrants in other countries.

Strengths And Limitations: This is the first study assessing the psychometric properties of the GIDYQ-AA in Chinese adolescents and young adults. The convergent and divergent validity of the GIDYQ-AA were not examined due to the unavailability of data. Also, the sample did not have an equal distribution of male to males and female to females.

Conclusion: The Chinese version of GIDYQ-AA is a useful measure, which could promote both the assessment and research of GD in the Chinese population. Wang Y, Feng Y, Su D, et al. Validation of the Chinese Version of the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. J Sex Med 2021;XX:XXX-XXX.
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http://dx.doi.org/10.1016/j.jsxm.2021.05.007DOI Listing
July 2021

Callous-unemotional traits in Chinese preschool children with attention-deficit/hyperactivity disorder.

Child Adolesc Psychiatry Ment Health 2021 Jul 10;15(1):35. Epub 2021 Jul 10.

Department of Psychology, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK.

Background: Children with early onset of Callous-Unemotional (CU) traits are at a higher risk for long-term, persistent psychosocial problems. The current study aimed to explore the characteristics of CU in preschool children with Attention Deficit Hyperactivity Disorder (ADHD) and the diagnostic significance of CU traits in ADHD.

Methods: A total of 176 preschool children (89 with ADHD and 87 Typically Developing Children [TDC]) aged 4-5 years old were recruited to the study. The participants were assessed for CU traits, emotional and behavioral problems, and how their executive functioning was associated with ADHD using multiple assessment scales. Multiple linear regression analysis was performed to assess the incremental validity of the Inventory of Callous-Unemotional Traits (ICU), adjusting for possible covariates by child's sex, conduct problems, and oppositional defiant symptoms.

Results: The results showed that there was a significant difference of ICU scores between the ADHD and TDC groups (F = 30.12, P < 0.001). In terms of callousness, ADHD + Oppositional Defiant Disorder (ODD) group showed a significant high score, and the ADHD only group scored significantly higher than the TDC group (F = 20.42, P < 0.001). The ICU was negatively associated with the prosocial behaviour subscale (γ = - 0.57, P < 0.01) and showed low to moderate positive correlations with emotional and behavioural problems, as well as executive function (γ = 0.24-0.67, P < 0.05). The ICU scores explained 6% of the incremental validity in ADHD symptoms. The diagnostic value of the ICU for ADHD was medium and acceptable.

Conclusions: The current study indicated that early identification of CU traits may help clinicians better understand symptoms and behavioural problems in children with ADHD. CU traits therefore could be considered as a useful assessment tool for ADHD.
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http://dx.doi.org/10.1186/s13034-021-00388-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272896PMC
July 2021

Assessing the post-treatment therapeutic effect of pinaverium in irritable bowel syndrome: a randomized controlled trial.

Sci Rep 2021 Jul 6;11(1):13894. Epub 2021 Jul 6.

The Macrohard Institute of Health, 231 North Ave., Battle Creek, MI, 49017, USA.

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder significantly decreasing patients' lives of quality and placing huge economic burden on our society. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued. It is clinically important to assess these post-treatment therapeutic effects (PTTE), which prevent IBS from relapsing. To assess the PTTE in pinaverium treatment and obtain high-quality evidence to justify the use of PTTE for long-term IBS management, we performed this controlled, double blind study on patients with IBS who were randomized to pinaverium 50 mg (n = 132) or placebo (n = 132), three times daily, for 4 weeks, and were followed up for 57 weeks after the treatments. The primary endpoints were abdominal pain and stool consistency. The secondary endpoints were pain frequency and stool frequency. The tertiary endpoints were global overall symptom and adverse events. Three days after pinaverium was discontinued, endpoints rebounded only 23.2-42.8% (P < 0.015 cf. placebo). The PTTE (P < 0.05 cf. placebo) lasted 9-17 weeks, which is similar to other antispasmodics with a 15-week treatment in striking contrast to ≥ 1 year PTTE in cognitive behavior therapy and < 1 week PTTE in serotonin antagonist treatment indicating that PTTE length markedly depends on the medication class used for the treatment and less depends on treatment length. After 17 weeks, the stage could be considered as an IBS natural history [no significant differences between pinaverium and placebo (all endpoints' P's > 0.05)], during which an average of 51.5-56.4% of patients (pool pinaverium and placebo data together) had IBS symptoms. These results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.Trial registration number: NCT02330029 (16/08/2016).
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http://dx.doi.org/10.1038/s41598-021-92990-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260803PMC
July 2021

Vestibular and oculomotor function in patients with vestibular migraine.

Am J Otolaryngol 2021 Jun 29;42(6):103152. Epub 2021 Jun 29.

Department of Geriatrics, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xi'an, Shaanxi 710032, China. Electronic address:

Aim: The purpose of this study was to assess the vestibular and oculomotor function in patients with vestibular migraine (VM). And we also investigate the relationship between testing results and effectiveness of preventive medications in VM.

Material And Method: 41 patients with VM were recruited in this study and examined with cervical and ocular vestibular evoked myogenic potential(cVEMP, oVEMP), video head impulse test(vHIT), caloric test and videonystagmography. All patients were treated with preventive medications. We calculated symptomatic improvement and record episodes frequency in patients with VM. Six months later, the effectiveness of preventive medications were evaluated and the relationship between vestibular testing and effectiveness of preventive medications were analyzed further.

Results: In vestibular function testing, 73% of patients with VM showed abnormal results. Abnormal cVEMP, oVEMP, vHIT, and caloric test were found in 20%, 44%, 32% and 56% respectively. The abnormal rate of oVEMP was significantly higher than that of cVEMP(p < 0.05). And the proportion of abnormal caloric test was obviously higher than that of vHIT (p < 0.05). In oculomotor function testing, 42% of the patients with VM showed pathological results which was significantly lower than that of vestibular function testing(p < 0.05). After 6 months follow-up, the proportion of prophylactic medication effectiveness was significantly higher in normal vestibular function testing group compared with the abnormal group (p < 0.05).

Conclusion: Abnormal vestibular and oculomotor functions are commonly observed in patients with VM. And these patients with abnormal vestibular function possess a weak effectiveness of preventive medications.
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http://dx.doi.org/10.1016/j.amjoto.2021.103152DOI Listing
June 2021

Gut microbiota is involved in the antidepressant-like effect of (S)-norketamine in an inflammation model of depression.

Pharmacol Biochem Behav 2021 Aug 1;207:173226. Epub 2021 Jul 1.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

The non-competitive glutamatergic N-methyl-d-aspartate receptor (NMDAR) antagonist, (R, S)-ketamine (ketamine), is known to exert rapid and long-lasting antidepressant-like effects. However, the widely use of ketamine is restricted owing to severe psychotomimetic side-effects and abuse liability. Very recently, we demonstrated that a major metabolite of ketamine, norketamine, in particular the (S)-enantiomer, had a potent antidepressant-like effect. We here examined the effects of a low-dose of norketamine enantiomers on depression symptoms and detected the changes in the composition of gut microbiota. In the behavioral tests, (S)-norketamine, but not (R)-norketamine, showed antidepressant-like effects in the lipopolysaccharide (LPS)-induced mice. At the genus level, (S)-norketamine, but not (R)-norketamine, significantly attenuated the increase in the levels of Escherichia-Shigella and Adlercreutzia, as well as the reduction in the levels of Harryflintia. At the species level, both (S)-norketamine and (R)-norketamine significantly attenuated the increase in the levels of bacterium ic1379 and Bacteroides sp. Marseille-P3166. Notably, (S)-norketamine was more potent than (R)-norketamine at reducing the levels of bacterium ic1379 and Bacteroides sp. Marseille-P3166. Furthermore, (S)-norketamine, but not (R)-norketamine, significantly attenuated the increased levels of Bacteroides caecigallinarum. In conclusion, this study suggests that the antidepressant-like effects of (S)-norketamine might be associated with the changes in the composition of gut microbiota. Therapeutic strategies improving the gut microbiota might facilitate the benefits for depression treatment.
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http://dx.doi.org/10.1016/j.pbb.2021.173226DOI Listing
August 2021

Synergistic Effects of the Jackfruit Seed Sourced Resistant Starch and subsp. on Suppression of Hyperlipidemia in Mice.

Foods 2021 Jun 21;10(6). Epub 2021 Jun 21.

Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China.

Approximately 17 million people suffer from cardiovascular diseases caused by hyperlipidemia, making it a serious global health concern. Among others, resistant starch (RS) has been widely used as a prebiotic in managing hyperlipidemia conditions. However, some studies have reported limited effects of RS on body weight and blood lipid profile of the host, suggesting further investigation on the synergistic effects of RS in combination with probiotics as gut microbes plays a role in lipid metabolism. This study evaluated the effects of jackfruit seed sourced resistant starch (JSRS) as a novel RS on mice gut microbes and hyperlipidemia by performing 16s rRNA and shotgun metagenomic sequencing. The results showed that 10% JSRS had a limited preventive effect on bodyweight and serum lipid levels. However, the JSRS promoted the growth of , which indicated the ability of for JSRS utilization. In the validation experiment, interacted with JSRS to significantly reduce bodyweight and serum lipid levels and had a therapeutic effect on hepatic steatosis in mice. Collectively, this study revealed the improvements of hyperlipidemia in mice by the synergistic effects of JSRS and , which will help in the development of "synbiotics" for the treatment of hyperlipidemia in the future.
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http://dx.doi.org/10.3390/foods10061431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235523PMC
June 2021

Computer-aided differentiates benign from malignant IPMN and MCN with a novel feature selection algorithm.

Math Biosci Eng 2021 05;18(4):4743-4760

The School of Information Science and Technology of Fudan University, Shanghai 200433, China.

In clinical practice, differentiating benign from malignant intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) preoperatively is crucial for deciding future treating algorithm. However, it remains challenging as benign and malignant lesions usually show similarities in both imaging appearances and clinical indices. Therefore, a robust and accurate computer-aided diagnosis (CAD) system based on radiomics and clinical indices was proposed in this paper to solve this dilemma. In the proposed CAD system, 107 patients were enrolled, where 90 cases were randomly selected for the training set with 5-fold cross validation to build the diagnostic model, while 17 cases were remained for an independent testing set to validate the performance. 436 high-throughput radiomics features while 9 clinical indices were designed and extracted. A novel feature selection algorithm named BLR (Bootstrapping repeated LASSO with Random selections) was proposed to select the most effective features. Then the selected features were sent to Support Vector Machine (SVM) to differentiate the benign or malignant. In the cross-validation cohort and independent testing cohort, the area under receiver operating characteristic curve (AUC) of CAD scheme were 0.83 and 0.92, respectively. The results fully prove the proposed CAD system achieves significant effect in tumors diagnosis.
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http://dx.doi.org/10.3934/mbe.2021241DOI Listing
May 2021

Exosomes from human umbilical cord mesenchymal stem cells inhibit ROS production and cell apoptosis in human articular chondrocytes via the miR-100-5p/NOX4 axis.

Cell Biol Int 2021 Jul 1. Epub 2021 Jul 1.

Department of Joint Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.

Cyclic strain-induced chondrocyte damage is actively involved in the pathogenesis of osteoarthritis and arthritis. MicroRNAs (miRNAs) carried by exosomes have been implicated in various diseases. However, the role of miR-100-5p in cyclic strain-induced chondrocyte damage remains to be elucidated. miR-100-5p and NADPH oxidase 4 (NOX4) were silenced or overexpressed in human primary articular chondrocytes. PKH-67 Dye was used to trace exosome endocytosis. Reactive oxygen species (ROS) production was monitored using DCFH-DA. Cell apoptosis was measured using a flow cytometer. Quantitative RT-PCR and Western blots were used to evaluate gene expression. Cyclic strain promoted ROS production and apoptosis in primary articular chondrocytes in a time-dependent manner. HucMSCs-derived exosomal miR-100-5p inhibited cyclic strain-induced ROS production and apoptosis in primary articular chondrocytes. miR-100-5p directly targeted NOX4. Overexpressing NOX4 attenuated hucMSCs-derived exosomes-mediated protective effects in primary articular chondrocytes. Cyclic strain promotes ROS production and apoptosis in primary articular chondrocytes, which was abolished by hucMSCs-derived exosomal miR-100-5p through its target NOX4. The findings highlight the importance of miR-100-5p/NOX4 axis in primary articular chondrocytes injury and provide new insights into therapeutic strategies for articular chondrocytes injury and osteoarthritis.
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http://dx.doi.org/10.1002/cbin.11657DOI Listing
July 2021

Non-concentrated aqueous electrolytes with organic solvent additives for stable zinc batteries.

Chem Sci 2021 Mar 15;12(16):5843-5852. Epub 2021 Mar 15.

College of Chemistry & Environmental Science, Key Laboratory of Analytical Science and Technology of Hebei Province, Hebei University Baoding 071002 China

Rechargeable aqueous zinc batteries (RAZBs) are promising for large-scale energy storage because of their superiority in addressing cost and safety concerns. However, their practical realization is hampered by issues including dendrite growth, poor reversibility and low coulombic efficiency (CE) of Zn anodes due to parasitic reactions. Here, we report a non-concentrated aqueous electrolyte composed of 2 m zinc trifluoromethanesulfonate (Zn(OTf)) and the organic dimethyl carbonate (DMC) additive to stabilize the Zn electrochemistry. Unlike the case in conventional aqueous electrolytes featuring typical Zn[HO] solvation, a solvation sheath of Zn with the co-participation of the DMC solvent and OTf anion is found in the formulated HO + DMC electrolyte, which contributes to the formation of a robust ZnF and ZnCO-rich interphase on Zn. The resultant Zn anode exhibits a high average CE of Zn plating/stripping (99.8% at an areal capacity of 2.5 mA h cm) and dendrite-free cycling over 1000 cycles. Furthermore, the HO + DMC electrolytes sustain stable operation of RAZBs pairing Zn anodes with diverse cathode materials such as vanadium pentoxide, manganese dioxide, and zinc hexacyanoferrate. Rational electrolyte design with organic solvent additives would promote building better aqueous batteries.
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http://dx.doi.org/10.1039/d0sc06734bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179661PMC
March 2021

The Significance of EEG Alpha Oscillation Spectral Power and Beta Oscillation Phase Synchronization for Diagnosing Probable Alzheimer Disease.

Front Aging Neurosci 2021 7;13:631587. Epub 2021 Jun 7.

Medical School of Chinese People's Liberation Army, Beijing, China.

Alzheimer disease (AD) is the most common cause of dementia in geriatric population. At present, no effective treatments exist to reverse the progress of AD, however, early diagnosis and intervention might delay its progression. The search for biomarkers with good safety, repeatable detection, reliable sensitivity and community application is necessary for AD screening and early diagnosis and timely intervention. Electroencephalogram (EEG) examination is a non-invasive, quantitative, reproducible, and cost-effective technique which is suitable for screening large population for possible AD. The power spectrum, complexity and synchronization characteristics of EEG waveforms in AD patients have distinct deviation from normal elderly, indicating these EEG features can be a promising candidate biomarker of AD. However, current reported deviation results are inconsistent, possibly due to multiple factors such as diagnostic criteria, sample sizes and the use of different computational measures. In this study, we collected two neurological tests scores (MMSE and MoCA) and the resting-state EEG of 30 normal control elderly subjects (NC group) and 30 probable AD patients confirmed by Pittsburgh compound B positron emission tomography (PiB-PET) inspection (AD group). We calculated the power spectrum, spectral entropy and phase synchronization index features of these two groups' EEG at left/right frontal, temporal, central and occipital brain regions in 4 frequency bands: δ oscillation (1-4 Hz), θ oscillation (4-8 Hz), α oscillation (8-13 Hz), and β oscillation (13-30 Hz). In most brain areas, we found that the AD group had significant differences compared to NC group: (1) decreased α oscillation power and increased θ oscillation power; (2) decreased spectral entropy in α oscillation and elevated spectral entropy in β oscillation; and (3) decrease phase synchronization index in δ, θ, and β oscillation. We also found that α oscillation spectral power and β oscillation phase synchronization index correlated well with the MMSE/MoCA test scores in AD groups. Our study suggests that these two EEG features might be useful metrics for population screening of probable AD patients.
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http://dx.doi.org/10.3389/fnagi.2021.631587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215164PMC
June 2021

Dynamics of dark breathers and Raman-Kerr frequency combs influenced by high-order dispersion.

Opt Express 2021 Jun;29(12):18095-18107

We investigate the dark breathers and Raman-Kerr microcombs generation influenced by stimulated Raman scattering (SRS) and high-order dispersion (HOD) effects in silicon microresonators with an integrated spatiotemporal formalism. The strong and narrow Raman gain constitute a threshold behavior with respect to free spectral range above which stable dark pulses can exist. The breathing dark pulses induced by HOD mainly depend on the amplitude and sign of third-order dispersion coefficient and their properties are also affected by the Raman assisted four wave mixing process. Such dissipative structures formed through perturbed switching waves, mainly exist in a larger red detuning region than that of stable dark pulses. Their breathing characteristics related to driving conditions have been analyzed in detail. Furthermore, the octave spanning mid-infrared (MIR) frequency combs via Cherenkov radiation are demonstrated, which circumvent chaotic and multi-soliton states compared with their anomalous dispersion-based counterpart. Our findings provide a viable way to investigate the physics inside dark pulses and broadband MIR microcombs generation.
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http://dx.doi.org/10.1364/OE.427718DOI Listing
June 2021

Neuropeptide ACP facilitates lipid oxidation and utilization during long-term flight in locusts.

Elife 2021 Jun 21;10. Epub 2021 Jun 21.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Long-term flight depends heavily on intensive energy metabolism in animals; however, the neuroendocrine mechanisms underlying efficient substrate utilization remain elusive. Here, we report that the adipokinetic hormone/corazonin-related peptide (ACP) can facilitate muscle lipid utilization in a famous long-term migratory flighting species, . By peptidomic analysis and RNAi screening, we identified brain-derived ACP as a key flight-related neuropeptide. gene expression increased notably upon sustained flight. CRISPR/Cas9-mediated knockout of gene and ACP receptor gene () significantly abated prolonged flight of locusts. Transcriptomic and metabolomic analyses further revealed that genes and metabolites involved in fatty acid transport and oxidation were notably downregulated in the flight muscle of ACP mutants. Finally, we demonstrated that a fatty-acid-binding protein (FABP) mediated the effects of ACP in regulating muscle lipid metabolism during long-term flight in locusts. Our results elucidated a previously undescribed neuroendocrine mechanism underlying efficient energy utilization associated with long-term flight.
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http://dx.doi.org/10.7554/eLife.65279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324298PMC
June 2021

RepSox effectively promotes the induced differentiation of sheep fibroblasts into adipocytes via the inhibition of the TGF‑β1/Smad pathway.

Int J Mol Med 2021 Aug 16;48(2). Epub 2021 Jun 16.

Department of Laboratory Medicine, School of Life Sciences, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China.

Previous reports have demonstrated that RepSox can function as a replacement for cMyc and Sox2 in the reprogramming of cells into induced pluripotent stem cells (iPSCs), as well as increasing the levels of bone morphogenetic protein (BMP)‑3 and inducing the phosphorylation of Smad1 in mouse embryonic stem cells. In the present study, it was demonstrated that RepSox caused the visible morphological transformation of sheep fibroblasts; however, no significant alterations in cell proliferation, apoptosis or chromosome aberrations were observed. Moreover, RepSox increased the plasticity of long‑term cryopreserved sheep fibroblasts, and further promoted differentiation into adipocytes. RepSox treatment led to a notable decrease in the expression of components of the transforming growth factor (TGF)‑β signaling pathway, particularly Smad2/3 phosphorylation. RepSox also activated the BMP pathway, promoted the reprogramming of cells from fibroblasts into adipocytes and induced mesenchymal‑epithelial transition. It is worth noting that RepSox notably increased the expression of octamer‑binding transcription factor 4 and L‑Myc, whereas Sox2 and Nanog expression were not detected. The results of high‑throughput RNA sequencing revealed that the levels of differentially expressed genes (DEGs) involved in various metabolic processes were markedly upregulated in the RepSox‑treated fibroblasts, while the DEGs in the majority of signaling pathways were markedly downregulated. On the whole, the present study demonstrates that RepSox can promote the plasticity of sheep fibroblasts and facilitates the differentiation of adipocytes via increasing BMP expression and inhibiting the activation of the TGF‑β signaling pathway.
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http://dx.doi.org/10.3892/ijmm.2021.4981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208630PMC
August 2021

Multiple functions of reversine on the biological characteristics of sheep fibroblasts.

Sci Rep 2021 Jun 11;11(1):12365. Epub 2021 Jun 11.

School of Laboratory Medicine, School of Life Sciences, Bengbu Medical College, Bengbu, 233000, China.

Previous reports have demonstrated that Reversine can reverse differentiation of lineage-committed cells to mesenchymal stem cells and suppress tumors growth. However, the molecular mechanisms of antitumor activity and promoting cellular dedifferentiation for reversine have not yet been clearly elucidated. In the present study, it was demonstrated that reversine of 5 μM could induce multinucleated cells through cytokinesis failure rather than just arrested in G2 or M phase. Moreover, reversine reversed the differentiation of sheep fibroblasts into MSC-like style, and notably increased the expression of pluripotent marker genes Oct4 and MSCs-related surface antigens. The fibroblasts treated with reversine could transdifferentiate into all three germ layers cells in vitro. Most importantly, the induced β-like cells and hepatocytes had similar metabolic functions with normal cells in vivo. In addition, reversine promoted fibroblasts autophagy, ROS accumulation, mitochondrial dysfunction and cell apoptosis via the mitochondria mediated intrinsic pathway. The results of high-throughput RNA sequencing showed that most differentially expressed genes (DEGs) involved in Mismatch repair, Nucleotide excision repair and Base excision repair were significantly up-regulated in reversine treated fibroblasts, which means that high concentration of reversine will cause DNA damage and activate the DNA repair mechanism. In summary, reversine can increase the plasticity of sheep fibroblasts and suppress cell growth via the mitochondria mediated intrinsic pathway.
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http://dx.doi.org/10.1038/s41598-021-91468-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196188PMC
June 2021
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