Publications by authors named "Si Wang"

249 Publications

Responsible genes in children with primary vesicoureteral reflux: findings from the Chinese Children Genetic Kidney Disease Database.

World J Pediatr 2021 May 31. Epub 2021 May 31.

Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wan Yuan Road, Shanghai, 201102, People's Republic of China.

Background: Primary vesicoureteral reflux (VUR) is a common congenital anomaly of the kidney and urinary tract (CAKUT) in childhood. The present study identified the possible genetic contributions to primary VUR in children.

Methods: Patients with primary VUR were enrolled and analysed based on a national multi-center registration network (Chinese Children Genetic Kidney Disease Database, CCGKDD) that covered 23 different provinces/regions in China from 2014 to 2019. Genetic causes were sought using whole-exome sequencing (WES) or targeted-exome sequencing.

Results: A total of 379 unrelated patients (male: female 219:160) with primary VUR were recruited. Sixty-four (16.9%) children had extrarenal manifestations, and 165 (43.5%) patients showed the coexistence of other CAKUT phenotypes. Eighty-eight patient (23.2%) exhibited impaired renal function at their last visit, and 18 of them (20.5%) developed ESRD at the median age of 7.0 (IQR 0.9-11.4) years. A monogenic cause was identified in 28 patients (7.39%). These genes included PAX2 (n = 4), TNXB (n = 3), GATA3 (n = 3), SLIT2 (n = 3), ROBO2 (n = 2), TBX18 (n = 2), and the other 11 genes (one gene for each patient). There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications (14.1% vs. 6%, P = 0.035). The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT (9.6% vs. 5.6%, P = 0.139, Chi-square test) and the grade of reflux (9.4% vs. 6.7%, P = 0.429). Kaplan-Meier survival curve showed that the presence of genetic mutations did affect renal survival (Log-rank test, P = 0.01). PAX2 mutation carriers (HR 5.1, 95% CI 1.3-20.0; P = 0.02) and TNXB mutation carriers (HR 20.3, 95% CI 2.4-168.7; P = 0.01) were associated with increased risk of progression to ESRD.

Conclusions: PAX2, TNXB, GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4% of monogenic VUR. Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR. Like other types of CAKUT, several genes may be responsible for isolated VUR.
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http://dx.doi.org/10.1007/s12519-021-00428-xDOI Listing
May 2021

Single-nucleus transcriptomic landscape of primate hippocampal aging.

Protein Cell 2021 May 30. Epub 2021 May 30.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.
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http://dx.doi.org/10.1007/s13238-021-00852-9DOI Listing
May 2021

Combined management can decrease blood pressure: an investigation of health-seeking behaviors among hypertensive patients in urban communities in China.

BMC Cardiovasc Disord 2021 May 25;21(1):256. Epub 2021 May 25.

Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background: Hypertensive patients can freely choose informal medical facilities, such as pharmacies, community health service centres, and cardiology clinics in secondary or tertiary hospitals, as routine places for medical treatment in China currently. The proportions, influencing factors and effects of different health-seeking behaviours on blood pressure (BP) among hypertensive patients in urban communities are not clear. The aim of the study was to investigate health-seeking behaviours and the effects of different health-seeking behaviours on BP among hypertensive patients in urban communities in China.

Methods: A cross-sectional survey of hypertension was conducted in urban communities in Chengdu. A total of 437 hypertensive patients seeking medical help regularly were sequentially enrolled to complete a the questionnaire on health-seeking behaviours.

Results: The average age was 67.1 ± 7.5 years old. The control rate of BP was 41.0%, and the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 144.2 ± 17.9 mm Hg and 75.4 ± 10.4 mm Hg, respectively. Among the hypertensive patients investigated, 62.8% chose community health service centre, 5.2% chose informal medical facilities, 21.5% chose cardiology clinics in secondary or tertiary hospitals, and 10.5% chose both community health service centre and cardiology clinics as the usual places for medical treatment. There were significant differences in education levels, proportions of home BP monitoring, establishment of chronic disease archives in the community, medication adherence and side effects of drugs among the four groups. The control rates of BP were 39.4%, 23.8%, 43.0% and 54.8% (P = 0.100), respectively. The SBPs were 145.1 ± 18.0, 150.9 ± 19.8, 143.8 ± 17.5 and 136.3 ± 15.1 mm Hg (P = 0.007), respectively, and it was significantly lower in the combined management group than in the other three groups. Compared with patients choosing community health service centre, patients in the combined management group had a significantly lower BP level (β = -0.119, P = 0.038) adjusting for age, sex, education level, establishment of chronic disease archives, medication adherence and number of antihypertensive drugs.

Conclusions: Combined management with both community health service centre and higher-level hospitals can decrease BP.
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http://dx.doi.org/10.1186/s12872-021-02073-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152143PMC
May 2021

Valproic Acid Induces Autism-Like Synaptic and Behavioral Deficits by Disrupting Histone Acetylation of Prefrontal Cortex ALDH1A1 in Rats.

Front Neurosci 2021 28;15:641284. Epub 2021 Apr 28.

Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing, China.

Objectives: This study aimed to investigate the impact of valproic acid (VPA) on the histone acetylation of acetaldehyde dehydrogenase 1A1 (ALDH1A1) and the mechanism underlying VPA-induced autism-like behavior.

Methods: Female Sprague-Dawley rats were intraperitoneally injected with VPA during gestation to establish an autism model in their offspring. Some offspring prenatally exposed to VPA were randomly treated with MS-275, one histone deacetylase (HDAC) inhibitor, or retinoic acid (RA) after birth. Behavioral tests were conducted on the offspring 6 weeks after birth. Electrophysiological experiments were performed to investigate long-term potentiation (LTP) in the prefrontal cortex (PFC). The expression levels of AMPA receptors (GluA1 and 2), NMDA receptors (GluN1 and 2), synapsin 1 (SYN1), HDAC, acetylated histone 3 (AcH3), RA receptor alpha (RARα), and ALDH1A1 in the PFC were measured by Western blotting and quantitative polymerase chain reaction. ALDH enzyme activity in PFC tissue was detected using a Micro ALDH Assay Kit. The RA level in the PFC was measured using ultrahigh-performance liquid chromatography/tandem mass spectrometry. A chromatin immunoprecipitation (ChIP) experiment explored the interaction between the ALDH1A1 gene and AcH3.

Results: Offspring prenatally exposed to VPA showed autism-like behavior, upregulated the levels of LTP and GluN2A, GluA1, and SYN1 proteins relevant to synaptic plasticity in the PFC. The expression levels of HDAC3 mRNA and protein were increased. On the other hand, there was a significant reduction in the levels of AcH3, RARα, RA, ALDH1A1 mRNA and protein, the level of ALDH activity and AcH3 enrichment in the ALDH1A1 promoter region in VPA-induced offspring. Administration of MS-275 in VPA offspring significantly elevated the levels of AcH3, ALDH1A1 mRNA and protein, ALDH activity, RA, the level of RARα protein and the binding of AcH3 to the ALDH1A1 promoter. In addition, the GluA1 protein level and LTP were reduced, and most behavioral deficits were reversed. After RA supplementation in the VPA-treated offspring, the RA and RARα protein levels were significantly upregulated, GluA1 protein and LTP were downregulated, and most autism-like behavioral deficits were effectively reversed.

Conclusion: These findings suggest that VPA impairs histoneacetylation of ALDH1A1 and downregulates the RA-RARα pathway. Such epigenetic modification of ALDH1A1 by VPA leads to autism-like synaptic and behavioral deficits.
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http://dx.doi.org/10.3389/fnins.2021.641284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113628PMC
April 2021

Vitamin A supplementation ameliorates motor incoordination via modulating RORα in the cerebellum in a valproic acid-treated rat autism model with vitamin A deficiency.

Neurotoxicology 2021 May 12;85:90-98. Epub 2021 May 12.

Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Chongqing Key Laboratory of Child Nutrition and Health, Chongqing, China. Electronic address:

Motor dysfunctions are common comorbidities among autism spectrum disorder (ASD) patients. Abnormal cerebellar development throughout critical periods may have an effect on motor functions and result in motor impairments. Vitamin A (VA) plays a crucial role in the developing process of the nervous system. The correlation of VA deficiency (VAD) and ASD with motor dysfunctions, however, is not clear. Therefore, we built rat models with different VA levels based on the valproic acid (VPA)-treated autism model. ASD rats with VAD showed aggravated motor coordination abnormalities, Purkinje cell loss and impaired dendritic arborization of Purkinje cells compared to ASD rats with normal VA levels (VA normal, VAN). Additionally, the expression levels of retinoid-related orphan receptor α (RORα) and retinoic acid receptor α (RARα) were lower in the cerebellum of ASD rats with VAD than in those of ASD rats with VAN. VA supplementation (VAS) effectively improved motor coordination and cerebellar Purkinje cell abnormalities in ASD rats with VAD. Furthermore, the results of chromatin immunoprecipitation (ChIP) assays confirmed that the enrichment of RARα was detected on the RORα promoter in the cerebellum and that VAS could upregulate the binding capacity of RARα for RORα promoters. These results showed that VAD in autism might result in cerebellar impairments and be a factor aggravating a subtype of ASD with motor comorbidities. The therapeutic effect of VAS on motor deficits and Purkinje neuron impairments in autism might be due to the regulation of RORα by RARα.
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http://dx.doi.org/10.1016/j.neuro.2021.05.004DOI Listing
May 2021

The short-term efficacy of electrical pudendal nerve stimulation versus intravesical instillation for the urethral pain syndrome: a randomized clinical trial.

World J Urol 2021 May 2. Epub 2021 May 2.

The Clinical Research Section, Shanghai Research Institute of Acupuncture and Meridian, 650 South Wanping Road, Shanghai, China.

Purpose: Urethral pain syndrome is a chronic condition characterized by disturbing feeling or server pain sensed at the urethra without specific treatment. This double-center, two-arm controlled trial aimed to explore the efficacy of electrical pudendal nerve stimulation (EPNS) versus intravesical instillation (II) of heparin and alkalinized lidocaine for urethral pain syndrome (UPS).

Methods: Eighty eligible patients took three sessions of EPNS, or 1 session of II per week, for 6 consecutive weeks. The primary end point was the change of pelvic pain and urgency/frequency symptom (PUF) score from baseline to week 6. Secondary outcome measures included changes of visual analogue scale (VAS) score and three sub-score extracted from PUF score.

Results: The enrolled participants were all included in the intention-to-treat analyses, and baseline characteristics between the two groups were well balanced. The post-treatment PUF score decreased by 10.0 (7.00, 16.50) in the EPNS group, and by 7.0 (3.00, 10.00) in the II group. At the closure of treatment, the medians of changes in symptom score, bother score, pain-related score and VAS score were 6.50 (4.25, 10.00), 4.00 (2.00, 6.00), 6.00 (5.00, 8.00),4.50 (2.25, 6.00), respectively, in the EPNS group, and 4.00 (2.00, 7.00), 3.00 (1.00, 3.00), 3.00 (2.00, 6.00), 2.00 (1.00, 4.00), respectively, in the II group. All the between-group differences were statistically significant.

Conclusion: Compared with the II, the EPNS results in superior pain control and better relief of lower urinary tract symptoms, and deserves further attention.

Trial Registration: ClinicalTrials.gov (NCT03671993).
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http://dx.doi.org/10.1007/s00345-021-03698-2DOI Listing
May 2021

Loss of microRNA-147 function alleviates synovial inflammation through ZNF148 in rheumatoid and experimental arthritis.

Eur J Immunol 2021 Apr 17. Epub 2021 Apr 17.

Department of Biochemistry and Molecular Biology, Institute of Molecular and Translational Medicine (IMTM), School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P. R. China.

MicroRNA-147 (miR-147) had been previously found induced in synoviocytes by inflammatory stimuli derived from T cells in experimental arthritis. This study was designed to verify whether loss of its function might alleviate inflammatory events in joints of experimental and rheumatoid arthritis (RA). Dark Agouti (DA) rats were injected intradermally with pristane to induce arthritis, and rno-miR-147 antagomir was locally administrated into individual ankle compared with negative control or rno-miR-155-5p antagomir (potential positive control). Arthritis onset, macroscopic severity, and pathological changes were monitored. While in vitro, gain or loss function of hsa-miR-147b-3p/hsa-miR-155-5p and ZNF148 was achieved in human synovial fibroblast cell line SW982 and RA synovial fibroblasts (RASF). The expression of miRNAs and mRNAs was detected by using RT-quantitative PCR, and protein expression was detected by using Western blotting. Anti-miR-147 therapy could alleviate the severity, especially for the synovitis and joint destruction in experimental arthritis. Gain of hsa-miR-147b-3p/hsa-miR-155-5p function in TNF-α stimulated SW982 and RASF cells could upregulate, in contrast, loss of hsa-miR-147b-3p/hsa-miR-155-5p function could downregulate the gene expression of TNF-α, IL-6, MMP3, and MMP13. Hence, such alteration could participate in synovial inflammation and joint destruction. RNAi of ZNF148, a miR-147's target, increased gene expression of TNF-α, IL-6, MMP3, and MMP13 in SW982 and RASF cells. Also, mRNA sequencing data showed that hsa-miR-147b-3p mimic and ZNF148 siRNA commonly regulated the gene expression of CCL3 and DEPTOR as well as some arthritis and inflammation-related pathways. Taken together, miR-147b-3p contributes to synovial inflammation through repressing ZNF148 in RA and experimental arthritis.
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http://dx.doi.org/10.1002/eji.202048850DOI Listing
April 2021

MicroRNA-497 Reduction and Increase of Its Family Member MicroRNA-424 Lead to Dysregulation of Multiple Inflammation Related Genes in Synovial Fibroblasts With Rheumatoid Arthritis.

Front Immunol 2021 26;12:619392. Epub 2021 Mar 26.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institute of Molecular and Translational Medicine (IMTM), Xi'an Jiaotong University Health Science Center, Xi'an, China.

Objectives: Mounting evidence has demonstrated that microRNAs (miRNAs) participate in rheumatoid arthritis (RA). The role of highly conserved miR-15/107 family in RA has not been clarified yet, and hence investigated in this study.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the expression of miRNAs and genes. Cell counting kit 8 (CCK-8) and FACS were used to detect proliferation and apoptosis. Protein expression was detected by using Western blotting. mRNA deep sequencing and cytokine antibody array were used to analyze differentially expressed genes, signaling pathways and cytokines.

Results: The expression of miR-15a, miR-103, miR-497, and miR-646 was found decreased, while miR-424 increased in RA patients. MiR-424 and miR-497 were further investigated and the results showed that they could regulate the expression of multiple genes in rheumatoid arthritis synovial fibroblast (RASF) and affect signaling pathways. At the protein level, miR-497 mimic altered all the selected inflammation-related genes while miR-424 inhibitor only affected part of genes. MiR-497 mimic, rather than miR-424 inhibitor, had significant effects on proliferation and apoptosis of RASF. DICER1 was found to positively regulate the expression of miR-424 and miR-497, while DICER1 was also negatively regulated by miR-424. The increase of miR-424 could reduce miR-497 expression, thus forming a loop, which facilitated explaining the dysregulated miR-424 and miR-497 in RA.

Conclusion: The miR-424 and miR-497 of miR-15/107 family affect cell proliferation and apoptosis in RA, and the proposed miR-424-DICER1-miR-497 feedback loop provides a novel insight into regulating miRNA expression and a candidate target for controlling RA.
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http://dx.doi.org/10.3389/fimmu.2021.619392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034293PMC
March 2021

Quantitative risk assessment of storm surge using GIS techniques and open data: A case study of Daya Bay Zone, China.

J Environ Manage 2021 Jul 8;289:112514. Epub 2021 Apr 8.

Hubei Key Laboratory of Marine Geological Resources/College of Marine Science and Technology, China University of Geosciences, Wuhan, 430074, China. Electronic address:

Storm surge is a natural disaster, often causing economic damage and loss of human life in the coastal communities. In recent decades, with more people attracted to coastal areas, the potential economic losses resulted from storm surges are increasing. Therefore, it is important to make risk assessments to identify areas at risk and design risk reduction strategies. However, the quantitative risk assessment of storm surge for coastal cities in China is often difficult due to the lack of adequate data regarding the building footprint and vulnerability curves. This paper aims to provide a methodology for conducting the quantitative risk assessment of storm surge, estimating direct tangible damage, by using Geographical Information System (GIS) techniques and open data. The proposed methodology was applied to a coastal area with a high concentration of petroleum industries in the Daya Bay zone. At first, five individual typhoon scenarios with different return periods (1000, 100, 50, 20, and 10 years) were defined. Then, the Advanced Circulation model and the Simulating Waves Nearshore model were utilized to simulate storm surge. The model outputs were imported into GIS software, transformed into inundation area and inundation depth. Subsequently, the building footprint data were extracted by the use of GIS techniques, including spatial analysis and image analysis. The layer containing building footprints was superimposed on the inundation area layer to identify and quantify the exposed elements to storm surge hazard. Combining the exposed elements with their related depth-damage functions, the quantitative risk assessment translates the spatial extent and depth of storm surge into the estimation of economic losses. The quantitative risk assessment and zonation maps for sub-zones in the study area can help local decision-makers to prioritize the sub-zones that are more likely to be affected by storm surge, make risk mitigation strategies, and develop long-term urban plans.
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http://dx.doi.org/10.1016/j.jenvman.2021.112514DOI Listing
July 2021

Three new sesquiterpenoid alkaloids from the roots of and its cytotoxicity.

Nat Prod Res 2021 Mar 26:1-9. Epub 2021 Mar 26.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, People's Republic of China.

Three new sesquiterpenoid alkaloids, cangorin K (), dimacroregelines C () and D (), as well as two known sesquiterpenoids (-), were isolated from the roots of The structures of new compounds were characterised by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data, and the known compounds were established by 1 D NMR spectra referring to the literatures. Cytotoxicity evaluation of these compounds against two human tumour lines (SMMC7721, LN229) was investigated by CCK-8 assay and displayed that compounds - showed potent cytotoxicity against SMMC7721 cell with IC value in the range of 0.26-9.67 μΜ and compounds - showed potent cytotoxicity against LN-229 cell with IC values in the range of 0.50-7.38 μΜ.
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http://dx.doi.org/10.1080/14786419.2021.1903460DOI Listing
March 2021

Stable and Efficient Nanofilm Pure Evaporation on Nanopillar Surfaces.

Langmuir 2021 Mar 17;37(12):3731-3739. Epub 2021 Mar 17.

School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, United Kingdom.

Molecular dynamics simulations were conducted to systematically investigate how to maintain and enhance nanofilm pure evaporation on nanopillar surfaces. First, the dynamics of the evaporation meniscus and the onset and evolution of nanobubbles on nanopillar surfaces were characterized. The meniscus can be pinned at the top surface of the nanopillars during evaporation for perfectly wetting fluid. The curvature of the meniscus close to nanopillars varies dramatically. Nanobubbles do not originate from the solid surface, where there is an ultrathin nonevaporation film due to strong solid-fluid interaction, but originate and evolve from the corner of nanopillars, where there is a quick increase in potential energy of the fluid. Second, according to a parametric study, the smaller pitch between nanopillars () and larger diameter of nanopillars () are found to enhance evaporation but also raise the possibility of boiling, whereas the smaller height of nanopillars () is found to enhance evaporation and suppress boiling. Finally, it is revealed that the nanofilm thickness should be maintained beyond a threshold, which is 20 Å in this work, to avoid the suppression effect of disjoining pressure on evaporation. Moreover, it is revealed that whether the evaporative heat transfer is enhanced on the nanopillar surface compared with the smooth surface is also affected by the nanofilm thickness. The value of nanofilm thickness should be determined by the competition between the suppression effect on evaporation due to the decrease in the volume of supplied fluid and the existence of capillary pressure and the enhancement effect on evaporation due to the increase in the heating area. Our work serves as the guidelines to achieve stable and efficient nanofilm pure evaporative heat transfer on nanopillar surfaces.
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http://dx.doi.org/10.1021/acs.langmuir.1c00236DOI Listing
March 2021

Development of a rat model for type 2 diabetes mellitus peri-implantitis: A preliminary study.

Oral Dis 2021 Mar 14. Epub 2021 Mar 14.

Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.

Objective: To develop an in vivo model to simulate the complex internal environment of diabetic peri-implantitis (T2DM-PI) model for a better understanding of peri-implantitis in type 2 diabetic patients.

Materials And Methods: Maxillary first molars were extracted in Sprague-Dawley (SD) rats, and customized cone-shaped titanium implants were installed in the extraction sites. Thereafter, implants were uncovered and customized abutments were screwed into implants. A high-fat diet and a low-dose injection of streptozotocin were utilized to induce T2DM. Finally, LPS was locally injected in implant sulcus to induce peri-implantitis.

Results: In the present study, T2DM-PI model has been successfully established. Imaging analysis revealed that abundant inflammatory cells infiltrated in the soft tissue in T2DM-PI group with concomitant excessive secretion of inflammatory cytokines. Moreover, higher expression of MMP and increased number of osteoclasts led to collagen disintegration and bone resorption in T2DM-PI group.

Conclusions: These results describe a novel rat model which stimulate T2DM-PI in vivo, characterized by overwhelming inflammatory response and bone resorption. This model has a potential to be used for investigation of initiation, progression and interventional therapy of T2DM-PI.
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http://dx.doi.org/10.1111/odi.13845DOI Listing
March 2021

SIRT3 consolidates heterochromatin and counteracts senescence.

Nucleic Acids Res 2021 05;49(8):4203-4219

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase linked to a broad range of physiological and pathological processes, including aging and aging-related diseases. However, the role of SIRT3 in regulating human stem cell homeostasis remains unclear. Here we found that SIRT3 expression was downregulated in senescent human mesenchymal stem cells (hMSCs). CRISPR/Cas9-mediated depletion of SIRT3 led to compromised nuclear integrity, loss of heterochromatin and accelerated senescence in hMSCs. Further analysis indicated that SIRT3 interacted with nuclear envelope proteins and heterochromatin-associated proteins. SIRT3 deficiency resulted in the detachment of genomic lamina-associated domains (LADs) from the nuclear lamina, increased chromatin accessibility and aberrant repetitive sequence transcription. The re-introduction of SIRT3 rescued the disorganized heterochromatin and the senescence phenotypes. Taken together, our study reveals a novel role for SIRT3 in stabilizing heterochromatin and counteracting hMSC senescence, providing new potential therapeutic targets to ameliorate aging-related diseases.
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http://dx.doi.org/10.1093/nar/gkab161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096253PMC
May 2021

Ultrasound-assisted closed reduction and percutaneous pinning for displaced and rotated lateral condylar humeral fractures in children.

J Shoulder Elbow Surg 2021 Feb 24. Epub 2021 Feb 24.

Department of Orthopedics Surgery, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

Background: It is difficult for surgeons to successfully perform closed reduction and percutaneous pinning on displaced and rotated lateral condylar humeral fractures in children. This study aimed to introduce an ultrasound-assisted closed reduction and percutaneous pinning technique and determine its usefulness in the treatment of displaced and rotated lateral condylar humeral fractures in children.

Methods: Between 2013 and 2018, 42 of 44 displaced and rotated pediatric lateral humeral condylar fractures were successfully treated with ultrasound-assisted closed reduction and percutaneous pinning. All surgical procedures were performed by 1 senior surgeon. Demographic and clinical data including age, sex, affected side, time from injury to reduction, operative time, and number of intraoperative radiographs (without fluoroscopy) were analyzed. Postoperative data were evaluated in terms of Kirschner wire in situ duration, follow-up duration, range of motion, carrying angle, cosmetic result, and complications.

Results: The average operative time was 67 minutes from 2013 to 2015 and 51 minutes from 2016 to 2018. All 42 patients who successfully underwent ultrasound-assisted closed reduction were followed up for >3 months, and 31 of 42 patients were followed up for >1 year. Among these 31 patients, the range-of-motion outcomes were excellent in 25 and good in 6. The carrying angle outcomes were excellent in 28 patients and good in 3. Two instances of wire infection, 9 instances of granulation tissue hyperplasia, and 23 instances of lateral spur formation occurred. No nonunion, avascular necrosis, or postoperative nerve issues were identified.

Conclusions: The surgical technique of ultrasound-assisted closed reduction and percutaneous pinning presented in this study can effectively help surgeons reduce displaced and rotated lateral condylar humeral fractures in children to avoid some open reductions and achieve satisfactory outcomes.
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http://dx.doi.org/10.1016/j.jse.2021.01.031DOI Listing
February 2021

Case Report: ST-Segment Elevation in a Man With Acute Pericarditis.

Front Cardiovasc Med 2020 23;7:609691. Epub 2020 Dec 23.

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.

Acute pericarditis is a rapid inflammatory condition of the pericardium with both infectious and non-infectious etiology. Most acute pericarditis is self-limited, with a small portion evolving rapidly. The definitive diagnosis of acute pericarditis often requires detailed physical examination, ECG, echocardiography, blood analysis and chest X-ray. It's usually challenging to distinguish acute pericarditis from ST-elevated myocardial infarction (STEMI) due to the similar ECG characteristics (ST segment change). Here we present a case of purulent pericarditis probably caused by esophageal perforation. A 52 year-old male presented with chest pain and dyspnea for 16 h. ST-segment elevation and positive cardiac markers lead to the initial diagnosis of ST-elevated myocardial infarction. Coronary angiography demonstrated normal coronary artery, while transthoracic echocardiography (TTE) showed massive pericardial effusion. Then, pericardiocentesis was performed with 250 ml of yellowish-green pus-like fluid extracted. A detailed history examination revealed a week history of possible esophageal perforation caused by a fishbone. And a further computed tomography (CT) demonstrated the presence of pneumomediastinum, and effusions in mediastinum, which lead to the diagnosis of purulent pericarditis. However, the patient's family refused further treatment and the patient died soon after discharge. The differential diagnosis of chest pain should include acute pericarditis, which can be equally critical and fatal. And it's important to note the peculiar characteristics of acute pericarditis, which include concave and diffused ST-segment elevation, PR segment depression, and the ratio of ST-segment elevation to T wave >0.24 in lead V6. Moreover, comprehensive medical history and physical examination are crucial to the differential diagnosis of chest pain patients.
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http://dx.doi.org/10.3389/fcvm.2020.609691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793765PMC
December 2020

Determining the stability of minimally displaced lateral humeral condyle fractures in children: ultrasound is better than arthrography.

J Orthop Surg Res 2021 Jan 9;16(1):32. Epub 2021 Jan 9.

Department of Pediatric Orthopedic Surgery, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, 100 Hong-Kong road, Wuhan, 430016, People's Republic of China.

Background: Evaluating of the articular cartilage status of the distal humeral epiphysis is difficult. Ultrasound imaging of the elbow is increasingly being used to confirm the integrity of the articular cartilage of minimally displaced lateral humeral condyle fractures in children with minimally displaced fractures. The aims of this study were to assess the correlations between ultrasound and arthrography findings for predicting the integrity of the cartilage hinge and to describe the utility of ultrasound in determining the need for pre-treatment.

Methods: Thirty-nine patients with minimally displaced lateral humeral condyle fractures who underwent ultrasound and arthrography examinations before surgery from May 2018 to December 2019 were included in this study. Ultrasound and arthrography predictors of the cartilage hinge status were independently measured. The ultrasound and arthrography results were compared.

Results: The mean displacement of the fractures was 3.1 mm (range, 2.0~5.0 mm). Arthrography showed incomplete fractures in 24 patients (61.5%) and complete fractures in 15 patients (38.5%). Ultrasound showed incomplete fractures in 25 patients (64.1%) and complete fractures in 14 patients (35.9%). The ultrasound and arthrography results of the integrity of the articular surface were consistent in 92.3% of the cases, including 23 that were predicted to have an intact articular surface and 13 that were predicted to have an incongruity articular surface. There was no correlation between the displacement and the fracture appearing complete on the ultrasound scan. The Pearson coefficient between ultrasound and arthrography for assessing the integrity of the articular surface was 0.837.

Conclusions: Ultrasound and arthrography assessments of the integrity of the cartilage hinge status appear to be highly consistent. Ultrasound can be used as a complementary tool with arthrography to predict the integrity of the cartilage hinge status in children with minimally displaced lateral humeral condyle fractures.

Level Of Evidence: Prospective study; level II.
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http://dx.doi.org/10.1186/s13018-020-02174-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797123PMC
January 2021

Age-related reductions in the excitability of phasic dorsal root ganglion neurons innervating the urinary bladder in female rats.

Brain Res 2021 Feb 7;1752:147251. Epub 2021 Jan 7.

Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250000, PR China. Electronic address:

Previous studies have revealed an impairment in bladder sensory transduction in aged animals. To examine the contributions of electrical property changes of bladder primary afferents to this impairment, we compared the electrical properties of dorsal root ganglion (DRG) neurons innervating the bladder among young (3 months), middle-aged (12 months), and old (24 months) female rats. The DRG neurons were labeled using axonal tracing techniques. Whole-cell current-clamp recordings of small and medium-sized neurons were performed to assess their passive and active properties. Two patterns of firing were identified based on responses to super-threshold stimuli (1.5, 2.0, 2.5, and 3.0 × rheobase): tonic neurons fired more action potentials (APs), whereas phasic neurons fired only one AP at the onset of stimulus. Tonic neurons were smaller and had a slower rate of AP rise, longer AP duration, more depolarized voltage threshold, and greater rheobase than phasic neurons. In phasic neurons, there was an age-associated increase in voltage threshold and an increase of rheobase (P < 0.05), suggesting an age-related decrease in excitability. In addition, both middle-aged and old rats had longer AP durations and slower rates of AP rise than young rats (P < 0.05). In tonic neurons, old rats had a greater AP overshoot and greater rate of AP rise, but no age-associated changes were identified in any other electrical properties. Our results suggest that the electrical properties of tonic and phasic bladder afferents are differentially altered with aging. A decrease in excitability may contribute to age-related reductions in bladder sensory function.
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http://dx.doi.org/10.1016/j.brainres.2020.147251DOI Listing
February 2021

Surfer Myelopathy in Children: A Case Series Study.

World Neurosurg 2021 Apr 5;148:e227-e241. Epub 2021 Jan 5.

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

Objective: The cause of surfer myelopathy remains enigmatic and long-term follow-up outcomes are not well documented. In the present study, the mechanisms underlying surfer myelopathy in children are analyzed and the long-term follow-up outcomes are reported.

Methods: Clinical data from 3 institutions were retrospectively analyzed. Patients were assessed using the American Spinal Injury Association Impairment Scale (AIS) on admission and at follow-up. The mechanisms were studied by analyzing patients' medical history, magnetic resonance imaging, and magnetic resonance angiography. The prognosis of long-term follow-up was summarized.

Results: Thirty-one children were diagnosed with surfer myelopathy. Intramedullary high-intensity T2 signal from mid to lower thoracic level to conus was found during the acute stage. Follow-up magnetic resonance imaging in the subacute stage showed cranial progression of the T2 hyperintensity up to 1-10 vertebral segments, and no neurologic deterioration was found. Intramedullary lesion length between the complete and incomplete injury was significantly different (P < 0.01) in the subacute phase. Flow voids around nerve roots and in the epidural space were detected in 18 patients and 15 patients, respectively, on axial T2-weighted imaging. Enlarged tortuous veins were found in 3 of 6 patients who underwent spinal magnetic resonance angiography, which were discontinuous around nerve root. During long-term follow-up, no patients with AIS grade A recovered, and atrophic cord was observed in the later stage in 14 patients. Patients with incomplete injury had different recoveries.

Conclusions: Surfer myelopathy in children is caused by spinal venous hypertension. The AIS grade on admission is a predictor of prognosis.
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http://dx.doi.org/10.1016/j.wneu.2020.12.135DOI Listing
April 2021

A genome-wide CRISPR-based screen identifies as a driver of cellular senescence.

Sci Transl Med 2021 Jan;13(575)

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

Understanding the genetic and epigenetic bases of cellular senescence is instrumental in developing interventions to slow aging. We performed genome-wide CRISPR-Cas9-based screens using two types of human mesenchymal precursor cells (hMPCs) exhibiting accelerated senescence. The hMPCs were derived from human embryonic stem cells carrying the pathogenic mutations that cause the accelerated aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome. Genes whose deficiency alleviated cellular senescence were identified, including , a histone acetyltransferase, which ranked as a top hit in both progeroid hMPC models. Inactivation of KAT7 decreased histone H3 lysine 14 acetylation, repressed transcription, and alleviated hMPC senescence. Moreover, lentiviral vectors encoding Cas9/sg-, given intravenously, alleviated hepatocyte senescence and liver aging and extended life span in physiologically aged mice as well as progeroid mice that exhibit a premature aging phenotype. CRISPR-Cas9-based genetic screening is a robust method for systematically uncovering senescence genes such as , which may represent a therapeutic target for developing aging interventions.
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http://dx.doi.org/10.1126/scitranslmed.abd2655DOI Listing
January 2021

A Single-Cell Transcriptomic Atlas of Human Skin Aging.

Dev Cell 2021 Feb 24;56(3):383-397.e8. Epub 2020 Nov 24.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Skin undergoes constant self-renewal, and its functional decline is a visible consequence of aging. Understanding human skin aging requires in-depth knowledge of the molecular and functional properties of various skin cell types. We performed single-cell RNA sequencing of human eyelid skin from healthy individuals across different ages and identified eleven canonical cell types, as well as six subpopulations of basal cells. Further analysis revealed progressive accumulation of photoaging-related changes and increased chronic inflammation with age. Transcriptional factors involved in the developmental process underwent early-onset decline during aging. Furthermore, inhibition of key transcription factors HES1 in fibroblasts and KLF6 in keratinocytes not only compromised cell proliferation, but also increased inflammation and cellular senescence during aging. Lastly, we found that genetic activation of HES1 or pharmacological treatment with quercetin alleviated cellular senescence of dermal fibroblasts. These findings provide a single-cell molecular framework of human skin aging, providing a rich resource for developing therapeutic strategies against aging-related skin disorders.
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http://dx.doi.org/10.1016/j.devcel.2020.11.002DOI Listing
February 2021

The Prognostic Value of F-Fluorodeoxyglucose PET/CT in the Initial Assessment of Primary Tracheal Malignant Tumor: A Retrospective Study.

Korean J Radiol 2021 03 19;22(3):425-434. Epub 2020 Nov 19.

Department of PET Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Objective: To investigate the potential value of F-fluorodeoxyglucose (FDG) PET/CT in predicting the survival of patients with primary tracheal malignant tumors.

Materials And Methods: An analysis of FDG PET/CT findings in 37 primary tracheal malignant tumor patients with a median follow-up period of 43.2 months (range, 10.8-143.2 months) was performed. Cox proportional hazards regression analyses were used to assess the associations between quantitative F-FDG PET/CT parameters, other clinic-pathological factors, and overall survival (OS). A risk prognosis model was established according to the independent prognostic factors identified on multivariate analysis. A survival curve determined by the Kaplan-Meier method was used to assess whether the prognosis prediction model could effectively stratify patients with different risks factors.

Results: The median survival time of the 37 patients with tracheal tumors was 38.0 months, with a 95% confidence interval of 10.8 to 65.2 months. The 3-year, 5-year and 10-year survival rate were 54.1%, 43.2%, and 16.2%, respectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value, age, pathological type, extension categories, and lymph node stage were included in multivariate analyses. Multivariate analysis showed MTV ( = 0.011), TLG ( = 0.020), pathological type ( = 0.037), and extension categories ( = 0.038) were independent prognostic factors for OS. Additionally, assessment of the survival curve using the Kaplan-Meier method showed that our prognosis prediction model can effectively stratify patients with different risks factors ( < 0.001).

Conclusion: This study shows that F-FDG PET/CT can predict the survival of patients with primary tracheal malignant tumors. Patients with an MTV > 5.19, a TLG > 16.94 on PET/CT scans, squamous cell carcinoma, and non-E1 were more likely to have a reduced OS.
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http://dx.doi.org/10.3348/kjr.2020.0211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909858PMC
March 2021

Internal daughter formation of Toxoplasma gondii tachyzoites is coordinated by transcription factor TgAP2IX-5.

Cell Microbiol 2021 03 8;23(3):e13291. Epub 2020 Dec 8.

Key Laboratory of Animal Epidemiology of Ministry of Agriculture, National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Toxoplasma gondii rapidly propagates through endodyogeny of tachyzoites, a process in which daughter parasites divide within the cell of the mother parasite. Recent studies have revealed that transcription factors with AP2-domain participate in the process of cell division in T. gondii. However, the concise regulation of the division cycles by AP2 proteins is poorly understood. In this study, we evaluated the effect of the transcription factor TgAP2IX-5 on the daughter cell formation in T. gondii. TgAP2IX-5 is a nuclear protein and is highly expressed during the S phase of the cell cycle of tachyzoites. TgAP2IX-5-disrupted strain showed a severe defect in replication and completely blocked lytic parasite growth. Following 3-indoleacetic acid treatment or without treatment of AP2IX-5-AID-3HA tagged strain for 30 min, 1 and 2 hr, the differentially expressed genes were 8, 54 and 202, respectively. Among these genes, the significantly downregulated ones were AP2 proteins, inner membrane complex (IMC) proteins and SAG-related proteins. Interestingly, loss of TgAP2IX-5 leads to a defect in internal daughter IMC formation and abnormalities in the morphology of organelles during cell division. Together, our study suggests that TgAP2IX-5 is crucial in regulating IMC formation of daughter cells in T. gondii.
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http://dx.doi.org/10.1111/cmi.13291DOI Listing
March 2021

Nanocomposites derived from licorice residues cellulose nanofibril and chitosan nanofibril: Effects of chitosan nanofibril dosage on resultant properties.

Int J Biol Macromol 2020 Dec 22;165(Pt B):2404-2411. Epub 2020 Oct 22.

Tianjin Key Laboratory of Pulp & Paper, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address:

Research on nanocomposite film from natural polymers such as cellulose and chitosan is of great importance to promote the development and highly efficient utilization of green and renewable bioresources. In this study, enzymatic pretreatment cellulose nanofibril (ETCNF) derived from licorice residues was prepared, and further processed into nanocomposite film with addition of chitosan nanofibril (CHN). This study focused on the effects of CHN dosage on the main properties of resultant nanocomposite film in terms of crystallinity, thermal stability, light transmittance, hydrophobicity, mechanical properties, and antibacterial activity. The results showed that ETCNF/CHN nanocomposite film exhibited good hydrophobicity especially at higher dosage of CHN, good light transmittance and mechanical properties (tensile strain can reach 39.6 MPa for ETCNF/CHN-10.0%). The as-prepared ETCNF/CHN nanocomposite film also showed good antibacterial activity against Escherichia coli. It was expected that the ETCNF/CHN nanocomposite film would help to realize transformation and high value-added utilization of these biomass residues.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.105DOI Listing
December 2020

Sixty-eight-year-old woman with a huge calcified aortic arch aneurysm.

Heart 2020 Nov;106(22):1739-1782

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China

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http://dx.doi.org/10.1136/heartjnl-2020-317577DOI Listing
November 2020

Internet-based patient- primary care physician-cardiologist integrated management model of hypertension in China: study protocol for a multicentre randomised controlled trial.

BMJ Open 2020 10 16;10(10):e039447. Epub 2020 Oct 16.

Cardiology, West China Hospital of Sichuan University, Chengdu, Sichaun, China

Introduction: The control rate of hypertension is low in China, especially in rural, western and minority areas. This is related to poor medical skills among physicians in primary care institutions and low levels of trust among patients. However, primary healthcare institutions are the main battleground for the prevention and treatment of hypertension. It is worth exploring how to most effectively integrate patients, primary care physicians and cardiologists in tertiary hospitals, to build a long-term mechanism for the prevention and treatment of hypertension. In this study, we aim to evaluate the clinical effectiveness and conduct a health economic evaluation of an internet-based patient-primary care physician-cardiologist integrated management model of hypertension in areas of China with different socioeconomic levels.

Methods And Analysis: This is a 12-month, multicentre, randomised controlled trial involving patients with hypertension in urban communities and rural areas of Sichuan Province, China. Each primary healthcare institution will cooperate with their tertiary hospital through the Red Shine Chronic Disease Management System (RSCDMS). Patients will be randomly assigned 1:1 to two groups: (1) a traditional care group; (2) an intervention group in which primary care physicians and cardiologists can share patient data and manage patients together through the RSCDMS. Patients can upload their blood pressure (BP) values and communicate with physicians using the system. The primary outcome is the change in systolic BP over a 12-month period. Secondary outcomes are changes in diastolic BP, BP control rate, values of 24-hour ambulatory BP monitoring, difference in cost-effectiveness between the groups, patient satisfaction, medication adherence and home BP monitoring compliance. All data will be recorded and stored in the RSCDMS and analysed using IBM SPSS V.26.0.

Ethics And Dissemination: This study has been approved by the Biomedical Research Ethics Committee of the West China Hospital of Sichuan University in Sichuan, China (No. 2020-148). Written informed consent will be obtained from all participants. The results of this study will be disseminated to the public through academic conferences and peer-reviewed journals.

Trial Registration Number: ChiCTR2000030677.
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http://dx.doi.org/10.1136/bmjopen-2020-039447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569994PMC
October 2020

Deciphering primate retinal aging at single-cell resolution.

Protein Cell 2020 Oct 14. Epub 2020 Oct 14.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

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http://dx.doi.org/10.1007/s13238-020-00791-xDOI Listing
October 2020

METTL3 counteracts premature aging via m6A-dependent stabilization of MIS12 mRNA.

Nucleic Acids Res 2020 11;48(19):11083-11096

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

N6-Methyladenosine (m6A) messenger RNA methylation is a well-known epitranscriptional regulatory mechanism affecting central biological processes, but its function in human cellular senescence remains uninvestigated. Here, we found that levels of both m6A RNA methylation and the methyltransferase METTL3 were reduced in prematurely senescent human mesenchymal stem cell (hMSC) models of progeroid syndromes. Transcriptional profiling of m6A modifications further identified MIS12, for which m6A modifications were reduced in both prematurely senescent hMSCs and METTL3-deficient hMSCs. Knockout of METTL3 accelerated hMSC senescence whereas overexpression of METTL3 rescued the senescent phenotypes. Mechanistically, loss of m6A modifications accelerated the turnover and decreased the expression of MIS12 mRNA while knockout of MIS12 accelerated cellular senescence. Furthermore, m6A reader IGF2BP2 was identified as a key player in recognizing and stabilizing m6A-modified MIS12 mRNA. Taken together, we discovered that METTL3 alleviates hMSC senescence through m6A modification-dependent stabilization of the MIS12 transcript, representing a novel epitranscriptional mechanism in premature stem cell senescence.
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http://dx.doi.org/10.1093/nar/gkaa816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641765PMC
November 2020

Genomic Study of Chinese Quadruple-negative GISTs Using Next-generation Sequencing Technology.

Appl Immunohistochem Mol Morphol 2021 01;29(1):34-41

Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, People's Republic of China.

Purpose: Approximately 10% of gastrointestinal stromal tumors (GISTs) are devoid of KIT, PDGFRA (platelet-derived growth factor-alpha), BRAF, and SDH alterations. The aim of this study was to characterize molecular drivers in Chinese patients with quadruple-negative GISTs.

Patients And Methods: In 1022 Chinese patients with GIST, mutations of KIT and PDGFRA were analyzed by direct sequencing. Of these mutations, 142 KIT/PDGFRA wild-type (WT) GISTs were detected, and succinate dehydrogenase (SDH) deficiency was determined using immunohistochemistry analysis of succinate dehydrogenase B. In 78 KIT/PDGFRA/SDH cases, we performed targeted 425 cancer-related gene analysis using next-generation sequencing. The correlation between molecular findings and clinicopathologic features was also analyzed.

Results: We defined 72 quadruple-negative GISTs from enrollments. They featured nongastric localization with histologic characteristics of spindle cells and male predilection. An overall 27.78% (20/72) of quadruple-negative tumors carried TP53, and 25.00% (18/72) carried RB1 mutations, which were frequently associated with high mitotic index and large size. TP53 analyses demonstrated coexistence with mutational activation of other oncogenes in 12 of 20 cases. A total of 18 RB1-mutated cases were independent of TP53. Further, no tumors carried NF1 and BRAF mutations.

Conclusions: We report the genomic analysis of Chinese quadruple-negative patients. These databases may help advance our understanding of quadruple-negative GISTs' progression. Next-generation sequencing from GISTs is feasible to provide relevant data for guiding individualized therapy.
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http://dx.doi.org/10.1097/PAI.0000000000000842DOI Listing
January 2021

Preparation of Cu/GO/Ti electrode by electrodeposition and its enhanced electrochemical reduction for aqueous nitrate.

J Environ Manage 2020 Dec 12;276:111357. Epub 2020 Sep 12.

School of Environmental Science and Engineering, Shaanxi University of Science & Technology, Xi'an, 710021, China; Shaanxi Key Laboratory of Green Preparation and Functionalization of Inorganic Materials, Xi'an, 710021, China.

A Cu/GO/Ti electrode was prepared by electrodeposition for removal of nitrate by means of the electrochemical reduction. The structure, morphology and characteristics of the electrode were characterized by scanning electron microscopy (SEM), Raman spectroscopy (RS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and electrochemical workstation, and Cu/GO/Ti was used as the cathode to remove nitrate in water by electrochemical process. Characterization results indicated that GO was successfully deposited on the Ti plate and it was partially reduced to reduced graphene. Dendritic and granular Cu particles are agglomerated on the surface of GO layer by chemical interaction in the form of metallic Cu, CuO and CuO, and the dendrite Cu layer increased the specific surface area of Cu layer. The addition of GO layer increases the electroreduction activity for nitrate. Furthermore, through comparison with Cu/Ti electrode, Cu/GO/Ti electrode improved the percentage of nitrate removal from 78.8% to 91.5%, and energy consumption decreased from 0.82 to 0.47 kW h/g NO-N. The present results showed the promising application of GO-based electrodes with Cu in electrocatalytic nitrate removal.
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http://dx.doi.org/10.1016/j.jenvman.2020.111357DOI Listing
December 2020

A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema.

J Clin Med 2020 Sep 10;9(9). Epub 2020 Sep 10.

Department of Ophthalmology, National University Hospital, Singapore S118177, Singapore.

(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species ( = 315), followed by serum ( = 309), then aqueous humor ( = 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers.
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http://dx.doi.org/10.3390/jcm9092920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564365PMC
September 2020