Publications by authors named "Fan Hu"

236 Publications

Genome and transcriptome sequencing of a newly isolated 2,4-dinitrophenol-degrading strain Rhodococcus imtechensis XM24D.

Genes Genomics 2021 May 1. Epub 2021 May 1.

College of Medicine, Xi'an International University, Xi'an, 710077, Shanxi, China.

Background: 2,4-Dinitrophenol (2,4-DNP) is an important organic environmental pollutant that is highly toxic to all forms of living organisms. A gram-positive strain (designated XM24D) was isolated from 2,4-DNP-contaminated soil by an enrichment technique.

Objective: The study was designed to analyze the ability of XM24D to degrade 2,4-DNP and its analogs and to reveal the degradation pathways of these aromatic compounds.

Methods: The degradation ability of XM24D was tested by a growth experiment. 2,4-DNP and its analog degradation pathways were predicted by genome and comparative transcriptome sequencing.

Results: Growth profiles showed that XM24D was able to utilize 2,4-DNP as the sole source of carbon, nitrogen and energy. Analogs of 2,4-DNP, including 4-nitrophenol (PNP) and 2-chloro-4-nitrophenol (2C4NP), can also be degraded by XM24D. Genome analysis showed that the XM24D genome contains two chromosomes with a combined size of 9.08 Mb and an average GC content of 67.07 %. Average nucleotide identity analysis indicated that Rhodococcus imtechensis RKJ300 is the most closely related strain to XM24D. Comparative transcriptome analysis revealed that the 2,4-DNP/PNP/2C4NP degradation pathway in XM24D is highly similar in sequence and organization to the 2,4-DNP degradation pathway in Rhodococcus opacus HL PM-1, the PNP degradation pathway in Rhodococcus opacus SAO101 and the 2C4NP degradation pathway in Rhodococcus imtechensis RKJ300. These results suggested that 2,4-DNP/PNP/2C4NP was degraded via the 2,4-dinitrocyclohexanone/4-nitrocatechol/hydroxyquinol pathway in XM24D.

Conclusions: Genomic and transcriptomic information on XM24D provides a valuable reference for further investigating the evolutionary characteristics of nitrophenol degradation pathways in microorganisms.
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http://dx.doi.org/10.1007/s13258-021-01101-3DOI Listing
May 2021

MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT.

Heliyon 2021 Apr 12;7(4):e06695. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China.

Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition. In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065298PMC
April 2021

Nemaline myopathy with dilated cardiomyopathy and severe heart failure: A case report.

Authors:
Qian Wang Fan Hu

World J Clin Cases 2021 Apr;9(11):2569-2575

Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

Background: Nemaline myopathy (NM) is a rare type of congenital myopathy, with an incidence of 1:50000. Patients with NM often exhibit hypomyotonia and varying degrees of muscle weakness. Skeletal muscles are always affected by this disease, while myocardial involvement is uncommon. However, with improvements in genetic testing technology, it has been found that NM with a mutation in the myopalladin () gene not only causes slow, progressive muscle weakness but also results in dilated or hypertrophic cardiomyopathy.

Case Summary: A 3-year-old pre-school boy was admitted to our hospital with cough, edema, tachypnea, and an increased heart rate. The patient was clinically diagnosed with severe dilated cardiomyopathy and heart failure, and subsequent gene examination confirmed the diagnosis of NM with a mutation in . Captopril, diuretics, low-dose digoxin, and dobutamine were administered. After 22 d of hospitalization, the patient was discharged due to the improvement of clinical symptoms. During the follow-up period, the patient died of refractory heart failure.

Conclusion: Decreased muscular tone and dilated cardiomyopathy are common features of -mutated NM. Heart transplantation may be a solution to this type of cardiomyopathy.
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http://dx.doi.org/10.12998/wjcc.v9.i11.2569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040187PMC
April 2021

Ga-DOTA-FAPI-04 PET/MR in the evaluation of gastric carcinomas: comparison with F-FDG PET/CT.

J Nucl Med 2021 Apr 16. Epub 2021 Apr 16.

Union Hospital, Tongji Medical College, Huazhong University of Science & Technology.

We sought to evaluate the performance of Ga-DOTA-FAPI-04 (Ga-FAPI) PET/MR for the diagnosis of primary tumor and metastatic lesions in patients with gastric carcinomas and to compare the results with those of F-FDG PET/CT. Twenty patients with histologically proven gastric carcinomas were recruited, and each patient underwent both F-FDG PET/CT and Ga-FAPI PET/MR. A visual scoring system was established to compare the detectability of primary tumors and metastases in different organs/regions (the peritoneum, abdominal lymph nodes, supradiaphragmatic lymph nodes, liver, ovary, bone, and other tissues). The original maximum standardized uptake value (SUV) and normalized SUV (calculated by dividing a lesion's original SUV with the mean SUV of the descending aorta) of selected lesions on both F-FDG PET/CT and Ga-FAPI PET/MR were measured. Original/normalized SUV-FAPI and SUV-FDG were compared for patient-based (including a single lesion with the highest activity uptake in each organ/region) and lesion-based (including all lesions [≤ 5] or the 5 lesions with highest activity [> 5]) analyses, respectively. The 20 recruited patients (median age: 56.0 y; range: 29-70 y) included 9 men and 11 women, 14 patients for initial staging and 6 for recurrence detection. Ga-FAPI PET was superior to F-FDG PET for primary tumor detection (100.00% [14/14] vs 71.43% [10/14], = 0.034), and the former had higher tracer uptake levels ( < 0.05). Ga-FAPI PET was superior to F-FDG PET in both patient-based and lesion-based evaluation except for the metastatic lesions in supradiaphragmatic lymph nodes and ovaries. Additionally, multiple sequences of MR images were beneficial for the interpretation of hepatic metastases in 3 patients, uterine and rectal metastases in 1 patient, ovarian lesions in 7 patients, and osseous metastases in 2 patients. Ga-FAPI PET/MR outperformed F-FDG PET/CT in visualizing the primary and most metastatic lesions of gastric cancer, and might be a promising method with the potential of replacing F-FDG PET/CT.
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http://dx.doi.org/10.2967/jnumed.120.258467DOI Listing
April 2021

Multi-PLI: interpretable multi-task deep learning model for unifying protein-ligand interaction datasets.

J Cheminform 2021 Apr 15;13(1):30. Epub 2021 Apr 15.

Guangdong-Hong Kong-Macao Joint Laboratory of Human-Machine Intelligence-Synergy Systems, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

The assessment of protein-ligand interactions is critical at early stage of drug discovery. Computational approaches for efficiently predicting such interactions facilitate drug development. Recently, methods based on deep learning, including structure- and sequence-based models, have achieved impressive performance on several different datasets. However, their application still suffers from a generalizability issue because of insufficient data, especially for structure based models, as well as a heterogeneity problem because of different label measurements and varying proteins across datasets. Here, we present an interpretable multi-task model to evaluate protein-ligand interaction (Multi-PLI). The model can run classification (binding or not) and regression (binding affinity) tasks concurrently by unifying different datasets. The model outperforms traditional docking and machine learning on both binary classification and regression tasks and achieves competitive results compared with some structure-based deep learning methods, even with the same training set size. Furthermore, combined with the proposed occlusion algorithm, the model can predict the important amino acids of proteins that are crucial for binding, thus providing a biological interpretation.
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http://dx.doi.org/10.1186/s13321-021-00510-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051026PMC
April 2021

New Silk Road: From Mesoscopic Reconstruction/Functionalization to Flexible Meso-Electronics/Photonics Based on Cocoon Silk Materials.

Adv Mater 2021 Apr 14:e2005910. Epub 2021 Apr 14.

College of Ocean and Earth Sciences, College of Materials, College of Physical Science and Technology, State Key Laboratory of Marine Environmental Science (MEL), Research Institute for Biomimetics and Soft Matter, Xiamen University, 422 Siming Nan Road, Xiamen, 361005, P. R. China.

Two of the key questions to be addressed are whether and how one can turn cocoon silk into fascinating materials with different electronic and optical functions so as to fabricate the flexible devices. In this review, a comprehensive overview of the unique strategy of mesoscopic functionalization starting from silk fibroin (SF) materials to the fabrication of various meso flexible SF devices is presented. Notably, SF materials with novel and enhanced properties can be achieved by mesoscopically reconstructing the hierarchical structures of SF materials. This is based on rerouting the refolding process of SF molecules by meso-nucleation templating. As-acquired functionalized SF materials can be applied to fabricate bio-compatible/degradable flexible/implantable meso-optical/electronic devices of various types. Consequently, functionalized SF can be fabricated into optical elements, that is, nonlinear photonic and fluorescent components, and make it possible to construct silk meso-electronics with high-performance. These advances enable the applications of SF-material based devices in the areas of physical and biochemical sensing, meso-memristors, transistors, brain electrodes, and energy generation/storage, applicable to on-skin long-term monitoring of human physiological conditions, and in-body sensing, information processing, and storage.
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http://dx.doi.org/10.1002/adma.202005910DOI Listing
April 2021

Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.

Aging (Albany NY) 2021 Apr 12;13(7):10749-10769. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen 518060, Guangdong, P.R. China.

Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration . We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic β-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions , suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.
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http://dx.doi.org/10.18632/aging.202895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064165PMC
April 2021

Highly Efficient Preparation of Single-Layer Two-Dimensional Polymer Obtained from Single-Crystal to Single-Crystal Synthesis.

J Am Chem Soc 2021 Apr 13;143(15):5636-5642. Epub 2021 Apr 13.

College of Polymer Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.

A two-dimensional polymer (2DP) single crystal () with submillimeter size was synthesized by single-crystal to single-crystal transformation based on photochemical [2 + 2]-cycloaddition. A successful conversion from monomer to polymer was achieved in the single-crystal state. The structure information with an atomic resolution of both the monomer and 2DP was given through single-crystal X-ray diffraction. By simply treated with trifluoroacetic acid (TFA) under mild conditions, an unprecedented efficiency of exfoliation was achieved. The triazine core in could be protonated by TFA, which resulted in a solution-like sample with >60% of monolayers. The size of the exfoliated monolayer reaches to several hundreds of μm. This is another precious example of 2DP single crystal with nearly perfect structure and large enough size. The successful preparation of the highly desirable 2DP "solution" for a long time containing large sized and large amount of 2DP monolayers may open up new prospects for the basic properties study and the applications of 2DPs.
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http://dx.doi.org/10.1021/jacs.1c00907DOI Listing
April 2021

Multivariate radiomics models based on F-FDG hybrid PET/MRI for distinguishing between Parkinson's disease and multiple system atrophy.

Eur J Nucl Med Mol Imaging 2021 Apr 7. Epub 2021 Apr 7.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China.

Purpose: To construct multivariate radiomics models using hybrid F-FDG PET/MRI for distinguishing between Parkinson's disease (PD) and multiple system atrophy (MSA).

Methods: Ninety patients (60 with PD and 30 with MSA) were randomized to training and test sets in a 7:3 ratio. All patients underwent F-fluorodeoxyglucose (F-FDG) PET/MRI to simultaneously obtain metabolic images (F-FDG), structural MRI images (T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and T2-weighted fluid-attenuated inversion recovery (T2/FLAIR)) and functional MRI images (susceptibility-weighted imaging (SWI) and apparent diffusion coefficient). Using PET and five MRI sequences, we extracted 1172 radiomics features from the putamina and caudate nuclei. The radiomics signatures were constructed with the least absolute shrinkage and selection operator algorithm in the training set, with progressive optimization through single-sequence and double-sequence radiomics models. Multivariable logistic regression analysis was used to develop a clinical-radiomics model, combining the optimal multi-sequence radiomics signature with clinical characteristics and SUV values. The diagnostic performance of the models was assessed by receiver operating characteristic and decision curve analysis (DCA).

Results: The radiomics signatures showed favourable diagnostic efficacy. The optimal model comprised structural (T1WI), functional (SWI) and metabolic (F-FDG) sequences (Radscore) with the area under curves (AUCs) of the training and test sets of 0.971 and 0.957, respectively. The integrated model, incorporating Radscore, three clinical symptoms (disease duration, dysarthria and autonomic failure) and SUV, demonstrated satisfactory calibration and discrimination in the training and test sets (0.993 and 0.994, respectively). DCA indicated the highest clinical benefit of the clinical-radiomics integrated model.

Conclusions: The radiomics signature with metabolic, structural and functional information provided by hybrid F-FDG PET/MRI may achieve promising diagnostic efficacy for distinguishing between PD and MSA. The clinical-radiomics integrated model performed best.
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http://dx.doi.org/10.1007/s00259-021-05325-zDOI Listing
April 2021

miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer's disease.

Nat Commun 2021 03 26;12(1):1903. Epub 2021 Mar 26.

Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.

Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer's disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD.
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http://dx.doi.org/10.1038/s41467-021-22196-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998005PMC
March 2021

Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression.

Front Immunol 2021 9;12:625957. Epub 2021 Mar 9.

Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured . The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.
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http://dx.doi.org/10.3389/fimmu.2021.625957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985449PMC
March 2021

SOX-17 is involved in invasion and apoptosis of colorectal cancer cells through regulating miR-302b-3p expression.

Cell Biol Int 2021 Mar 19. Epub 2021 Mar 19.

Department One of Anorectal Surgery, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.

The prognosis of advanced colorectal cancer (CRC) is currently still very poor, which suggests that the biological mechanisms of CRC oncogenesis are not fully understood. This study was conducted to explore the regulatory effect of SOX-17 on the expression of microRNA (miR)-302b-3p, and the involvement of SOX-17 in the invasion and apoptosis of CRC cells. The expression of SOX-17 and miR-302a,b,c,d-3p in colorectal cancer and normal colon epithelial cell lines was measured by real-time polymerase chain reaction and/or western blot. The regulatory effects of SOX-17 on miR-302b-3p gene in HT29 and LoVo cells were tested using the ChiP assay. The biological activities of SOX-17 and miR-302b-3p were evaluated by invasion and apoptosis assay. Results showed that transfection of SOX-17 small interfering RNA (siSOX-17) significantly increased, whereas transfection of SOX-17 overexpression vector (oeSOX-17) significantly decreased, miR-302b expression in HT29 and LoVo cells. Cotransfection of oeSOX-17 and miR-302b-3p inhibitor (INmiR-302b) significantly blocked the effects of SOX-17 in HT29 and LoVo cells. ChIP experiments showed that SOX-17 bonded to the miR-302b-3p promoter in HT29 and LoVo cells. Transfection of oeSOX-17 and miR-302b-3p mimics (MImiR-302b) significantly decreased, whereas transfection of siSOX-17 and INmiR-302b significantly increased, the invasion of HT29 and LoVo cells. In contrast, transfection of oeSOX-17 and MImiR-302b significantly increased, while transfection of siSOX-17 and INmiR-302b significantly decreased, apoptosis in HT29 and LoVo cells. Cotransfection of oeSOX-17 and INmiR-302b significantly blocked the effects of oeSOX-17 on cell invasion and apoptosis in HT29 and LoVo cells. These results suggested that SOX-17 can bind to the promoter of miR-302b-3p gene to regulate its expression, while both SOX-17 and miR-302b regulate the invasion and apoptosis in colorectal cancer cells.
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http://dx.doi.org/10.1002/cbin.11594DOI Listing
March 2021

Author Correction: A novel pathway regulates social hierarchy via lncRNA AtLAS and postsynaptic synapsin IIb.

Cell Res 2021 May;31(5):601

Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

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http://dx.doi.org/10.1038/s41422-021-00492-yDOI Listing
May 2021

A head-to-head comparison of Ga-DOTA-FAPI-04 and F-FDG PET/MR in patients with nasopharyngeal carcinoma: a prospective study.

Eur J Nucl Med Mol Imaging 2021 Feb 20. Epub 2021 Feb 20.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China.

Purpose: To conduct a head-to-head comparison of the diagnostic ability of Ga-DOTA-FAPI-04 (Ga-FAPI) and F-FDG PET/MR in nasopharyngeal carcinoma (NPC) patients.

Methods: Patients diagnosed with NPC were prospectively enrolled. All patients underwent head-and-neck Ga-FAPI PET/MR and F-FDG PET/MR within 1 week. Primary tumor, lymph node numbers, and tracer uptake were compared by SUVmax and visual evaluation. The primary tumor volumes derived from Ga-FAPI, F-FDG PET, and MRI were also compared.

Results: Fifteen patients were enrolled from June to August 2020. Both Ga-FAPI and F-FDG PET had 100% detection rate of the primary tumor. The Ga-FAPI SUVmax of primary tumors (13.87 ± 5.13) was lower than that of F-FDG (17.73 ± 6.84), but the difference was not significant (p = 0.078). Compared with F-FDG, Ga-FAPI PET improved the delineation of skull-base invasion in eight out of eight patients and intracranial invasion in four out of four patients. When 25%SUVmax of Ga-FAPI or 20%SUVmax of F-FDG was utilized as a threshold for determining tumor volume, it was highly consistent with MRI. F-FDG PET detected much more positive lymph nodes than Ga-FAPI (100 vs 48). The SUVmax of 48 paired lymph nodes was significantly lower on Ga-FAPI than F-FDG (8.67 ± 3.88 vs 11.79 ± 6.17, p < 0.001). Additionally, Ga-FAPI further detected four highly suspected small, distant metastases in three patients. Compared with F-FDG, Ga-FAPI changed overall staging in six of fifteen patients, with three patients being up-staged, and three down-staged.

Conclusion: Ga-FAPI outperforms F-FDG in delineating the primary tumor and detecting suspected distant metastases, particularly in the evaluation of skull-base and intracranial invasion, suggesting Ga-FAPI hybrid PET/MR has the potential to serve as a single-step staging modality for patients with NPC. However, its value regarding lymph node and distant metastases evaluation needs further study.

Trial Registration: NCT04554719. Registered September 8, 2020 - retrospectively registered, http://clinicaltrails.gov/show/NCT04554719.
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http://dx.doi.org/10.1007/s00259-021-05255-wDOI Listing
February 2021

Association between kidney stones and risk of developing stroke: a meta-analysis.

Neurol Sci 2021 Feb 19. Epub 2021 Feb 19.

Department of Neurology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, No. 152, Aiguo Road, Nanchang, 330006, Jiangxi, China.

Background: Many studies have described the relationship between kidney stones and stroke, but the results are controversial, so we conducted this meta-analysis to estimate the relationship between kidney stones and the risk of developing stroke.

Methods: Studies were marked with a comprehensive search of PubMed, EMBASE, Google, and ISI Web of Science databases through 25 March 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and a random-effects model or fix-effects model was used to compute the pooled combined risk estimate. Heterogeneity was reported as I. We performed subgroup and sensitivity analysis to assess potential sources of heterogeneity.

Results: Eight studies of seven articles involving 3,526,808 participants were included in the meta-analysis. Overall, kidney stones were associated with a moderate risk of stroke incidence (HR, 1.24; 95% CI, 1.11-1.40; I=79.6%; p=0.000). We conducted a sensitivity analysis by removing the studies that had a high risk of bias. Heterogeneity subsequently decreased significantly, while an increased risk of stroke in patient with kidney stones was again demonstrated (HR, 1.16; 95% CI, 1.11-1.23; I=28.7%; p=0.000). Stratifying analysis showed that the results were more pronounced for ischemic stroke (HR, 1.14; 95% CI, 1.08-1.22; I=15.6%; p=0.00) and the follow-up duration ≥10 years (HR, 1.18; 95% CI, 1.10-1.27; I=31.6%; p=0.003).

Conclusions: Our meta-analysis suggests that patients with kidney stones may have a modestly increased risk of developing stroke, especially in ischemic stroke. More large-scaled and clinical trials should be done to identify the relative impact of kidney stones on stroke outcomes in the future.
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http://dx.doi.org/10.1007/s10072-021-05113-5DOI Listing
February 2021

Identification of Three Significant Genes Associated with Immune Cells Infiltration in Dysfunctional Adipose Tissue-Induced Insulin-Resistance of Obese Patients via Comprehensive Bioinformatics Analysis.

Int J Endocrinol 2021 22;2021:8820089. Epub 2021 Jan 22.

Department of Cardiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.

Background: Low-grade chronic inflammation in dysfunctional adipose tissue links obesity with insulin resistance through the activation of tissue-infiltrating immune cells. Numerous studies have reported on the pathogenesis of insulin-resistance. However, few studies focused on genes from genomic database. In this study, we would like to explore the correlation of genes and immune cells infiltration in adipose tissue via comprehensive bioinformatics analyses and experimental validation in mice and human adipose tissue.

Methods: Gene Expression Omnibus (GEO) datasets (GSE27951, GSE55200, and GSE26637) of insulin-resistant individuals or type 2 diabetes patients and normal controls were downloaded to get differently expressed genes (DEGs), and GO and KEGG pathway analyses were performed. Subsequently, we integrated DEGs from three datasets and constructed commonly expressed DEGs' PPI net-works across datasets. Center regulating module of DEGs and hub genes were screened through MCODE and cytoHubba in Cytoscape. Three most significant hub genes were further analyzed by GSEA analysis. Moreover, we verified the predicted hub genes by performing RT qPCR analysis in animals and human samples. Besides, the relative fraction of 22 immune cell types in adipose tissue was detected by using the deconvolution algorithm of CIBERSORT (Cell Type Identification by Estimating Relative Subsets of RNA Transcripts). Furthermore, based on the significantly changed types of immune cells, we performed correlation analysis between hub genes and immune cells. And, we performed immunohistochemistry and immunofluorescence analysis to verify that the hub genes were associated with adipose tissue macrophages (ATM).

Results: Thirty DEGs were commonly expressed across three datasets, most of which were upregulated. DEGs mainly participated in the process of multiple immune cells' infiltration. In protein-protein interaction network, we identified , , and as hub genes. GSEA analysis suggested high expression of the three hub genes was correlated with immune cells functional pathway's activation. Immune cell infiltration and correlation analysis revealed that there were significant positive correlations between and M0 macrophages, and M0 macrophages, Plasma cells, and CD8 T cells. Finally, hub genes were associated with ATMs infiltration by experimental verification.

Conclusions: This article revealed that , , and were potential hub genes associated with immune cells' infiltration and the function of proinflammation, especially adipose tissue macrophages, in the progression of obesity-induced diabetes or insulin-resistance.
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http://dx.doi.org/10.1155/2021/8820089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850849PMC
January 2021

Contrasting detoxification mechanisms of Chlamydomonas reinhardtii under Cd and Pb stress.

Chemosphere 2021 Jan 25;274:129771. Epub 2021 Jan 25.

College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Chlamydomonas reinhardtii has been frequently investigated for its resistance to metals; however, few studies have systematically compared the intracellular and extracellular processes involved in the detoxification of Cd and Pb by this microalga. We found that C. reinhardtii was more tolerant to Pb (concentration for 50% of the maximal effect; EC50: 29.48 ± 8.83 mg L) than to Cd (EC50: 12.48 ± 1.30 mg L) after 96 h of exposure. Extracellular polymeric substances (EPS), intracellular starch granules, lipid droplets, and glutathione were significantly increased under Cd and Pb treatments. Lead-containing particles were formed outside of the cells exposed to 30 mg L of Pb, whereas no minerals were present when Cd was added. Various EPS functional groups, including -COOH, C-O-C (polysaccharides), and amide I and II (proteins), were involved in the interactions with Cd and Pb. The Pb removal rate (60.46-78.27%) by C. reinhardtii was higher than that of Cd (50.61-59.38%), and the microalgal cells with intact EPS bound more metals than those without EPS. Adsorption accounted for 79.62% of the total Cd accumulation in the low-Cd treatment, whereas absorption dominated the Pb accumulation at low Pb concentrations. The distributions of Cd and Pb in and out of the microalgal cells were reversed when the concentrations of the two metals increased. The detoxification strategies of C. reinhardtii for Cd and Pb were completely different, and these findings may assist in the phycoremediation of metal pollution in aquatic environments.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129771DOI Listing
January 2021

Cerebrospinal fluid changes and clinical features of aseptic meningitis in patients with Kawasaki disease.

J Int Med Res 2021 Feb;49(2):300060520980213

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Objective: To assess the distinguishing features of aseptic meningitis (AM) in patients with Kawasaki disease (KD) compared with bacterial meningitis (BM) patients.

Methods: Thirty-eight patients with KD and 126 patients with BM were retrospectively investigated. The following clinical manifestations and laboratory parameters were compared between the two groups: duration of fever before lumbar puncture, conjunctival injection, oral cavity changes, rash, cervical lymphadenopathy and extremity changes, vomiting, front fontanel bulging, neck stiffness, leukocyte number, hemoglobin level, platelet number, C-reactive protein level, cerebrospinal fluid (CSF) content, liver enzyme level, and urinalysis.

Results: Vomiting and neck stiffness were more prevalent in patients with BM. KD patients with AM showed elevated blood leukocyte numbers and C-reactive protein levels in the early febrile stage. CSF glucose was significantly lower in patients with BM compared with KD patients with AM. Receiver operating characteristic curve analysis showed that the optimal cutoff value of CSF glucose for discrimination of BM and AM/KD was 2.945 mmol/L, with a sensitivity of 84.2% and a specificity of 71.4%.

Conclusions: Detailed investigations of clinical manifestation and laboratory parameters are necessary to distinguish AM and BM in patients with KD. Decreased CSF glucose is a potential indicator of BM.
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http://dx.doi.org/10.1177/0300060520980213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871089PMC
February 2021

Bola3 Regulates Beige Adipocyte Thermogenesis Maintaining Mitochondrial Homeostasis and Lipolysis.

Front Endocrinol (Lausanne) 2020 11;11:592154. Epub 2021 Jan 11.

Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA , we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis.
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http://dx.doi.org/10.3389/fendo.2020.592154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829353PMC
January 2021

A novel carbon-11 radiolabeled maternal embryonic leucine zipper kinase inhibitor for PET imaging of triple-negative breast cancer.

Bioorg Chem 2021 Feb 5;107:104609. Epub 2021 Jan 5.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Molecular Imaging, Wuhan 430022, China. Electronic address:

Maternal embryonic leucine zipper kinase (MELK) plays an important role in the regulation of tumor cell growth. It is abundant in triple-negative breast cancers (TNBC), making it a promising target for molecular imaging and therapy. Based on the structure of a potent MELK inhibitor (OTSSP167) with high affinity, we developed a novel carbon-11 radiolabeled molecular probe C-methoxy-OTSSP167, and evaluated its application in positron emission tomography (PET) imaging of TNBC. C-methoxy-OTSSP167 was successfully synthesized and was identical to its non-radiolabeled compound methoxy-OTSSP167 in high-pressure liquid chromatography (HPLC) chromatogram. The obtained tracer had 10 ± 2% radiolabeling yield with a total synthesis time of 40 min. The radiochemical purity of the tracer was more than 95%. The maximum uptake (9.97 ± 0.70%) of C-methoxy-OTSSP167 in MELK-overexpressing MDA-MB-231 cells was at 60 min in vitro. On PET, MDA-MB-231 tumors were clearly visible at 30, 60, and 90 min after injection of C-methoxy-OTSSP167, while no obvious radioactivity accumulation was found in the low-MELK MCF-7 tumors. In vivo biodistribution data were consistent with the findings of the PET images. However, the radioactive tracer showed high uptake in normal organs such as liver and intestine, which may limit the application of the tracer. In addition, a markedly different MELK expression level in MDA-MBA-231 and MCF-7 tumors was verified via IHC staining. In conclusion, C-methoxy-OTSSP167 was successfully developed and exhibited elevated uptake in MELK overexpressed tumor, indicating its potential for noninvasively imaging of MELK overexpressed TNBC.
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http://dx.doi.org/10.1016/j.bioorg.2020.104609DOI Listing
February 2021

Nonuniform Electric Field-Enhanced In-Source Declustering in High-Pressure Photoionization/Photoionization-Induced Chemical Ionization Mass Spectrometry for Operando Catalytic Reaction Monitoring.

Anal Chem 2021 Feb 7;93(4):2207-2214. Epub 2021 Jan 7.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning 116023, People's Republic of China.

Photoionization mass spectrometry (PI-MS) is a powerful and highly sensitive analytical technique for online monitoring of volatile organic compounds (VOCs). However, due to the large difference of PI cross sections for different compounds and the limitation of photon energy, the ability of lamp-based PI-MS for detection of compounds with low PI cross sections and high ionization energies (IEs) is insufficient. Although the ion production rate can be improved by elevating the ion source pressure, the problem of generating plenty of cluster ions, such as [MH]·(HO) ( = 1 and 2) and [M], needs be solved. In this work, we developed a new nonuniform electric field high-pressure photoionization/photoionization-induced chemical ionization (NEF-HPPI/PICI) source with the abilities of both HPPI and PICI, which was accomplished through ion-molecule reactions with high-intensity HO reactant ions generated by photoelectron ionization (PEI) of water molecules. By establishing a nonuniform electric field in a three-zone ionization region to enhance in-source declustering and using 99.999% helium as the carrier gas, not only the formation of cluster ions was significantly diminished, but the ion transmission efficiency was also improved. Consequently, the main characteristic ion for each analyte both in HPPI and PICI occupied more than 80%, especially [HCOOH·H] with a yield ratio of 99.2% for formic acid. The analytical capacity of this system was demonstrated by operando monitoring the hydrocarbons and oxygenated VOC products during the methanol-to-olefins and methane conversion catalytic reaction processes, exhibiting wide potential applications in process monitoring, reaction mechanism research, and online quality control.
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http://dx.doi.org/10.1021/acs.analchem.0c04081DOI Listing
February 2021

Amino Acid Catabolism During Nitrogen Limitation in .

Front Plant Sci 2020 17;11:589026. Epub 2020 Dec 17.

Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Diatoms can accumulate high levels of triacylglycerols (TAGs) under nitrogen depletion and have attracted increasing attention as a potential system for biofuel production. In , a model diatom, about 40% of lipid is synthesized from the breakdown of cellular components under nitrogen starvation. Our previous studies indicated that carbon skeletons from enhanced branched-chain amino acid (BCAA) degradation under nitrogen deficiency contribute to TAG biosynthesis in . In this review, we outlined the catabolic pathways of all 20 amino acids based on the genome, transcriptome, proteome, and metabolome data. The contribution of these amino acid catabolic pathways to TAG accumulation was also analyzed.
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http://dx.doi.org/10.3389/fpls.2020.589026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780933PMC
December 2020

Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer's disease.

Cell Death Differ 2021 Jan 4. Epub 2021 Jan 4.

Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.

Iron homeostasis disturbance has been implicated in Alzheimer's disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer's mouse model and Alzheimer's patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpn mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpn and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.
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http://dx.doi.org/10.1038/s41418-020-00685-9DOI Listing
January 2021

Subcutaneous Energy/Signal Transmission Based on Silk Fibroin Up-Conversion Photonic Amplification.

ACS Nano 2020 Dec 31. Epub 2020 Dec 31.

Department of Physics, National University of Singapore, 2 Science Drive 3, Singapore 117542, Singapore.

Transmission of energy and signals through human skin is critically important for implantable devices. Because near-infrared (NIR) light can easily penetrate through human skin/tissue, in this study we report on silk fibroin (SF) up-conversion photonic amplifiers (SFUCPAs) integrated into optoelectronic devices, which provide a practical approach for subcutaneous charging and communication NIR lasers. SFUCPAs achieve a 4 times higher fluorescence than the control, which gives rise to a 47.3 time increase in subcutaneous NIR energy conversion efficiency of a single fibrous dye-sensitized solar cell compared with the control. Moreover, the hybrid printed electrodes exhibited reversible switching to NIR exposure with a response time of ∼1.06/1.63 s for a 3 s ON/OFF switch. Owing to the flexible, biocompatible, and cost-efficient design NIR-driven optoelectronic performance, the SFUCPAs are promising for use in applications of subcutaneous medical electronics for charging, storing information, and controlling implanted devices.
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http://dx.doi.org/10.1021/acsnano.0c09575DOI Listing
December 2020

Nomogram Based on Risk Factors for Type 2 Diabetes Mellitus Patients with Coronary Heart Disease.

Diabetes Metab Syndr Obes 2020 18;13:5025-5036. Epub 2020 Dec 18.

School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Introduction: This study aimed to study risk factors for coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) patients and establish a clinical prediction model.

Research Design And Methods: A total of 3402 T2DM patients were diagnosed by clinical doctors and recorded in the electronic medical record system (EMRS) of six Community Health Center Hospitals from 2015 to 2017, including the communities of Huamu, Jinyang, Yinhang, Siping, Sanlin and Daqiao. From September 2018 to September 2019, 3361 patients (41 patients were missing) were investigated using a questionnaire, physical examination, and biochemical index test. After excluding the uncompleted data, 3214 participants were included in the study and randomly divided into a training set (n = 2252) and a validation set (n = 962) at a ratio of 3:1. Through lead absolute shrinkage and selection operator (LASSO) regression analysis and logistic regression analysis of the training set, risk factors were determined and included in a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were used to validate the distinction, calibration and clinical practicality of the model.

Results: Age, T2DM duration, hypertension (HTN), hyperuricaemia (HUA), body mass index (BMI), glycosylated haemoglobin A1c (HbA1c), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were significant factors in this study. The C-index was 0.750 (0.724-0.776) based on the training set and 0.767 (0.726-0.808) based on the validation set. Through ROC analysis, the set area was 0.750 for the training set and 0.755 for the validation set. The calibration test indicated that the S:P of the prediction model was 0.982 in the training set and 0.499 in the validation set. The decision curve analysis showed that the threshold probability of the model was 16-69% in the training set and 16-73% in the validation set.

Conclusion: Based on community surveys and data analysis, a prediction model of CHD in T2DM patients was established.
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http://dx.doi.org/10.2147/DMSO.S273880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756175PMC
December 2020

Rat BAT xenotransplantation recovers the fertility and metabolic health of PCOS mice.

J Endocrinol 2021 Feb;248(2):249-264

State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.

Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5-10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation, fortunately, did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.
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http://dx.doi.org/10.1530/JOE-20-0068DOI Listing
February 2021

Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus.

CNS Neurosci Ther 2020 12 26;26(12):1230-1240. Epub 2020 Nov 26.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Idiopathic normal pressure hydrocephalus (iNPH), the most common type of adult-onset hydrocephalus, is a potentially reversible neuropsychiatric entity characterized by dilated ventricles, cognitive deficit, gait apraxia, and urinary incontinence. Despite its relatively typical imaging features and clinical symptoms, the pathogenesis and pathophysiology of iNPH remain unclear. In this review, we summarize current pathogenetic conceptions of iNPH and its pathophysiological features that lead to neurological deficits. The common consensus is that ventriculomegaly resulting from cerebrospinal fluid (CSF) dynamics could initiate a vicious cycle of neurological damages in iNPH. Pathophysiological factors including hypoperfusion, glymphatic impairment, disturbance of metabolism, astrogliosis, neuroinflammation, and blood-brain barrier disruption jointly cause white matter and gray matter lesions, and eventually lead to various iNPH symptoms. Also, we review the current treatment options and discuss the prospective treatment strategies for iNPH. CSF diversion with ventriculoperitoneal or lumboperitonealshunts remains as the standard therapy, while its complications prompt attempts to refine shunt insertion and develop new therapeutic procedures. Recent progress on advanced biomaterials and improved understanding of pathogenesis offers new avenues to treat iNPH.
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http://dx.doi.org/10.1111/cns.13526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702234PMC
December 2020

Perilipin 4 Protein: an Impending Target for Amyotrophic Lateral Sclerosis.

Mol Neurobiol 2021 Apr 26;58(4):1723-1737. Epub 2020 Nov 26.

Department of Neurology, Jiangxi Provincial People's Hospital, Affiliated People's Hospital of Nanchang University, Nanchang, China.

The pathogenesis of amyotrophic lateral sclerosis (ALS) might exist some relationships with the abnormal lipidomic metabolisms. Therefore, we observed and analyzed the alteration of perilipin 4 (PLIN 4) distribution in the anterior horns (AH); the central canals (CC) and its surrounding gray matter; the posterior horns (PH); and the anterior, lateral, and posterior funiculus (AF, LF, and PF) of the cervical, thoracic, and lumbar segments, as well as the alteration of PLIN 4 expression in the entire spinal cords at the pre-onset, onset, and progression stages of Tg(SOD1*G93A)1Gur (TG) mice and the same period of wild-type(WT) by fluorescent immunohistochemistry, the Western blot, and the image analysis. Results showed that the PLIN 4 distributions in the spinal AH, CC and its surrounding gray matter, PH, AF, and PF of the cervical, thoracic, and lumbar segments in the TG mice at the pre-onset, onset, and progression stages significantly increased compared with those at the same periods of WT mice; the gray matter was especially significant. No significant changes were detected in the LF. PLIN 4 extensively distributed in the neurons and the proliferation neural cells. The PLIN 4 distributions significantly gradually increased from the pre-onset to onset to progression stages, and significantly correlated with the gradual increase death of neural cells. Total PLIN 4 expression in the spinal cords of TG mice significantly increased from the pre-onset, to onset, and to progression stages compared with that in the WT mice. Our data suggested that the PLIN 4 distribution and expression alterations might participate in the death of neural cells in the pathogenesis of ALS through modulating the lipidomic metabolisms and the neural cell proliferation.
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http://dx.doi.org/10.1007/s12035-020-02217-5DOI Listing
April 2021

Resistant dextrin reduces obesity and attenuates adipose tissue inflammation in high-fat diet-fed mice.

Int J Med Sci 2020 20;17(17):2611-2621. Epub 2020 Sep 20.

Department of Endocrinology, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.

Resistant dextrin (RD), a short chain glucose polymer, has been shown to improve type 2 diabetes mellitus (T2DM) in clinical studies. However, the improvement of adipose tissue inflammation and specific mechanisms of RD supplementation in obesity have not been fully investigated. Therefore, we examined whether RD attenuates obesity and adipose tissue inflammation in high-fat diet (HFD)-fed mice. Male C57BL/6 mice were fed a chow diet, a HFD or a HFD with RD supplementation for 12 weeks. Body weight (BW), fasting blood glucose (FBG), epididymal fat accumulation, serum total triglyceride (TG), free fatty acid (FFA) and inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IL-10) were measured. Inflammation markers and macrophage infiltration in epididymal adipose tissue were observed. After 12 weeks of intervention, the body weight gain of mice in RD supplementation group was less than that in HFD group. FBG, epididymal fat accumulation, serum TG and FFA levels were reduced in RD supplementation group compared with HFD group. Moreover, serum and mRNA levels of IL-6 were significantly reduced in the RD supplementation group. In addition, RD supplementation reduced macrophage infiltration, regulated polarization of macrophage and inhibited NF-κB signaling in epididymal adipose tissue. In conclusion, RD reduces obesity and attenuates adipose tissue inflammation in HFD-fed mice, and the inhibition of NF-κB signaling may be a presumed mechanism for its effects.
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http://dx.doi.org/10.7150/ijms.45723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645326PMC
September 2020

Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells.

Cell Death Dis 2020 10 30;11(10):937. Epub 2020 Oct 30.

Guangdong Key Laboratory for Genome Stability & Disease Prevention and Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, People's Republic of China.

Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.
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http://dx.doi.org/10.1038/s41419-020-03130-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599338PMC
October 2020