Publications by authors named "Zhihua Wang"

355 Publications

Potential correlation between depression-like behavior and the MAPK pathway in the rat hippocampus following spinal cord injury.

World Neurosurg 2021 Jul 13. Epub 2021 Jul 13.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi,People's Republic of China. Electronic address:

Depression induced by spinal cord injury (SCI) has been demonstrated in clinical and experimental studies; it significantly impacts patients' lives and may be associated with changes in the hippocampus. However, the biological mechanisms underlying depression after SCI are unknown. The mitogen-activated protein kinase (MAPK) signaling pathway participates in the potential mechanisms of depression; however, it is unknown whether the pathway plays a role in SCI-induced depression. We applied an animal model of depression induced by SCI, established using an aneurysm clip, to determine whether MAPK activation in the hippocampus is associated with depression-like behavior. The results showed that SCI led to depression-like behavior such as anhedonia in the sucrose preference test, decreased number of crossings in the open field test, decreased body weight, and decreased immobility time in the forced swim test. Western blot analysis further showed that SCI significantly increased the levels of phosphorylated p38MPAK (p-p38MPAK) and cleaved caspase-3 in the hippocampus and inhibited the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2). In addition, there were significant negative correlations between depression-like behavior and p-ERK1/2, and positive correlations between depression-like behavior and p-p38MPAK and cleaved caspase-3. These findings suggest that the MAPK pathway in the rat hippocampus may be involved in the pathophysiology of depression induced by SCI.
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http://dx.doi.org/10.1016/j.wneu.2021.06.093DOI Listing
July 2021

Sex-based clinical and immunological differences in COVID-19.

BMC Infect Dis 2021 Jul 5;21(1):647. Epub 2021 Jul 5.

Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Background: Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.

Methods: We performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.

Results: We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.

Conclusions: Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
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http://dx.doi.org/10.1186/s12879-021-06313-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256650PMC
July 2021

Aberrant MCM10 SUMOylation induces genomic instability mediated by a genetic variant associated with survival of esophageal squamous cell carcinoma.

Clin Transl Med 2021 Jun;11(6):e485

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the common gastrointestinal malignancy with an inferior prognosis outcome. DNA replication licensing aberration induced by dysregulation of minichromosome maintenance proteins (MCMs) causes genomic instability and cancer metastasis. SUMOylation modification plays a pivotal role in regulation of genomic integrity, while its dysregulation fueled by preexisting germline variants in cancers remains poorly understood.

Methods: Firstly, we conducted two-stage survival analysis consisting of an exome-wide association study in 904 ESCC samples and another independent 503 ESCC samples. Then, multipronged functional experiments were performed to illuminate the potential biological mechanisms underlying the promising variants, and MCM10 influences the ESCC progression. Finally, we tested the effects of MCM10 inhibitors on ESCC cells.

Results: A germline variant rs2274110 located at the exon 15 of MCM10 was identified to be significantly associated with the prognosis of ESCC patients. Individuals carrying rs2274110-AA genotypes confer a poor survival (hazard ratio = 1.61, 95% confidence interval = 1.35-1.93, p = 1.35 × 10 ), compared with subjects carrying rs2274110-AG/GG genotypes. Furthermore, we interestingly found that the variant can increase SUMOylation levels at K669 site (Lys[K]699Arg[R]) of MCM10 protein mediated by SUMO2/3 enzymes, which resulted in an aberrant overexpression of MCM10. Mechanistically, aberrant overexpression of MCM10 facilitated the proliferation and metastasis abilities of ESCC cells in vitro and in vivo by inducing DNA over-replication and genomic instability, providing functional evidence to support our population finding that high expression of MCM10 is extensively presented in tumor tissues of ESCC and correlated with inferior survival outcomes of multiple cancer types, including ESCC. Finally, MCM10 inhibitors Suramin and its analogues were revealed to effectively block the metastasis of ESCC cells.

Conclusions: These findings not only demonstrate a potential biological mechanism between aberrant SUMOylation, genomic instability and cancer metastasis, but also provide a promising biomarker aiding in stratifying ESCC individuals with different prognosis, as well as a potential therapeutic target MCM10.
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http://dx.doi.org/10.1002/ctm2.485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236122PMC
June 2021

LncRNA LINC00963 promotes osteogenic differentiation of hBMSCs and alleviates osteoporosis progression by targeting miRNA-760/ETS1 axis.

Autoimmunity 2021 Jun 29:1-13. Epub 2021 Jun 29.

Department of Spine Surgery, The First Affiliated Hospital of Dali University, Dali City, PR China.

Although long non-coding RNA LINC00963 has been reported to play a crucial regulatory role in osteoporosis (OP), its specific mechanism has not been well studied. Cell viability of human bone marrow mesenchymal stem cells (hBMSCs) transfected with short hairpin RNA targeting LINC00963 (sh-LINC00963) and negative control (sh-NC) was analysed by cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity in hBMSCs transfected with sh-LINC00963 and sh-NC after induction by osteogenic medium (OM) on day 7 was detected. The protein expression levels of osteocalcin (OCN) and osteopontin (OPN) in hBMSCs transfected with sh-LINC00963 and sh-NC during OM induction on day 3 were detected by western blot. The relationship among LINC00963, miR-760, and E26 transformation specific-1 (ETS1) was determined by bioinformatics analysis, luciferase reporter assay, and RNA-binding protein immunoprecipitation (RIP) assay. A rat model with OP was established to confirm the role of LINC00963 . The expression level of LINC00963 was much lower in hBMSCs isolated from the discarded femoral head tissues of OP patients compared with that in health patients. Meanwhile, the expression level of LINC00963 was significantly increased and the expression level of miR-760 was decreased in hBMSCs during osteogenic induction. LINC00963 could bind to the 3'-untranslated region (3'-UTR) of miR-760 and negatively regulate the expression of miR-760, then promote the osteogenic differentiation in hBMSCs. ETS1 was identified as a target of miR-760. Moreover, overexpression of LINC00963 obviously reduced bone mineral density (BMD) of the left femur in OP rats and alleviated OP progression Our results demonstrated that LINC00963 positively regulated the expression of ETS1 by directly targeting miR-760, and then promoted osteogenic differentiation of hBMSCs , and also attenuated OP progression , suggesting that LINC00963 might be a potential therapeutic target for OP.
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http://dx.doi.org/10.1080/08916934.2021.1922890DOI Listing
June 2021

Function of histone methylation and acetylation modifiers in cardiac hypertrophy.

J Mol Cell Cardiol 2021 Jun 24;159:120-129. Epub 2021 Jun 24.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, Shenzhen, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Cardiac hypertrophy is an adaptive response of the heart to increased workload induced by various physiological or pathological stimuli. It is a common pathological process in multiple cardiovascular diseases, and it ultimately leads to heart failure. The development of cardiac hypertrophy is accompanied by gene expression reprogramming, a process that is largely dependent on epigenetic regulation. Histone modifications such as methylation and acetylation are dynamically regulated under cardiac stress. These consequently contribute to the pathogenesis of cardiac hypertrophy via compensatory or maladaptive transcriptome reprogramming. Histone methylation and acetylation modifiers play crucial roles in epigenetic remodeling during the pathogenesis of cardiac hypertrophy. Regulation of histone methylation and acetylation modifiers serves as a bridge between signal transduction and downstream gene reprogramming. Exploring the role of histone modifiers in cardiac hypertrophy provides novel therapeutic strategies to treat cardiac hypertrophy and heart failure. In this review, we summarize the recent advancements in functional histone methylation and acetylation modifiers in cardiac hypertrophy, with an emphasis on the underlying mechanisms and the therapeutic potential.
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http://dx.doi.org/10.1016/j.yjmcc.2021.06.011DOI Listing
June 2021

Characteristics of patients with kidney injury associated with COVID-19.

Int Immunopharmacol 2021 Jul 19;96:107794. Epub 2021 May 19.

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

To explore the characteristics of COVID-19 infection related kidney injury, we retrospectively collected cases of COVID-19 patients with definite clinical outcomes (discharge or death) and relevant laboratory results from Jan 3 to Mar 30, 2020 in Tongji hospital, Wuhan, China. 1509 patients were included, 1393 cases with normal baseline serum creatinine, and 116 cases with elevated baseline serum creatinine (EBSC). On admission, the prevalence of elevated serum creatinine, elevated blood urea nitrogen (BUN) and estimated glomerular filtration (eGFR) under 60 ml/min/1.73 m were 7.7%, 6.6% and 7.2%, respectively. The incidence of in-hospital death in the patients with EBSC was 7.8%, which was significantly higher than those with normal serum creatinine (1.2%). Inflammatory, immunological, and organ damage indices were relatively higher in the EBSC group, in which lymphocytes, albumin, and hemoglobin were significantly lower. Kaplan-Meier analysis revealed age above 65 years, males, comorbidities (especially for cardiovascular disease and tumor patients), lymphocyte count < 1.5 × 10/L, leukocyte count > 10 × 10/L, EBSC, eGFR < 60 ml/min/1.73 m were associated with in-hospital death. Multivariate Cox proportional hazard regression confirmed that EBSC (HR: 2.643, 95% CI: 1.111-6.285, P = 0.028), eGFR < 60 ml/min/1.73 m (HR: 3.889, 95% CI: 1.634-9.257, P = 0.002), were independent risk factors after adjusting for age, sex, any comorbidity, leukocyte and lymphocyte count. Therefore, the prevalence of kidney injury in patients with COVID-19 was high and associated with in-hospital mortality. Early detection and effective intervention of kidney injury may reduce COVID-19 deaths.
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http://dx.doi.org/10.1016/j.intimp.2021.107794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133528PMC
July 2021

De novo design of a pH-triggered self-assembled β-hairpin nanopeptide with the dual biological functions for antibacterial and entrapment.

J Nanobiotechnology 2021 Jun 14;19(1):183. Epub 2021 Jun 14.

Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin, People's Republic of China.

Background: Acid-tolerant enteric pathogens can evade small intestinal acid barriers, colonize and infect the intestinal tract. However, broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function.

Results: A pH-triggered dual biological functional self-assembled peptide (SAP) was designed according to the features of amino-acid building blocks and the diagonal cation-π interaction principle. The results of characterization experiments showed that changes in pH conditions could trigger microstructural transformation of the nanopeptide from nanospheres to nanofibers. The subsequent antibacterial and toxicity experiments determined that SAP had great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus above 15.6 μg/mL under acidic conditions by disrupting bacterial membrane integrity, excellent biocompatibility in vitro even at 250 μg/mL and high tolerance in physical environment. Moreover, at peptide concentrations greater than 62.5 μg/mL, SAP showed the entrapment property, which played an important role in phagocytic clearance in infection forces. Meanwhile, the in vivo results revealed that SAP possessed excellent therapeutic effect and good biosafety.

Conclusions: Our study revealed the antibacterial activity of a short β-hairpin forming self-assembled peptide, and established an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infections.
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http://dx.doi.org/10.1186/s12951-021-00927-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201815PMC
June 2021

CircMYBL2 regulates the resistance of cervical cancer cells to paclitaxel via miR-665-dependent regulation of EGFR.

Drug Dev Res 2021 May 27. Epub 2021 May 27.

Department of Oncology, The First People's Hospital of Jingmen Affiliated to Hubei Minzu University, Jingmen, Hubei, China.

Circular RNAs are considered to be associated with cancer resistance. This study aims to investigate the function and mechanism of circMYBL2 in paclitaxel (PTX) resistance of cervical cancer (CC). The expression of circMYBL2, miR-665 and epidermal growth factor receptor (EGFR) was investigated using quantitative real-time polymerase chain reaction assay. Cell viability, cell colony number, cell proliferation, apoptosis and lactate dehydrogenase (LDH) were detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, flow cytometry and LDH release assays, respectively. The interaction between miR-665 and circMYBL2 or EGFR was confirmed by dual-luciferase reporter assay. The protein expression levels were quantified by western blot or immunohistochemistry assay. Mice xenograft models were constructed to investigate the effect of circMYBL2 on CC tumor growth. CircMYBL2 was upregulated in CC tissues and cells, especially in PTX-resistant CC tissues and cells, and it was a stable circRNA mainly distributed in the cytoplasm. CircMYBL2 could enhance the PTX resistance of CC cells in vitro and promote CC tumor growth in vivo. Mechanistically, circMYBL2 could inhibit the PTX sensitivity and promote cell malignant behaviors in PTX-sensitive and PTX-resistant CC cells via upregulating EGFR mediated by miR-665. CircMYBL2 played a positive role in the PTX resistance and malignant activities of PTX-sensitive and PTX-resistant CC cells by regulating the miR-665/EGFR network, providing a novel therapeutic strategy for the treatment of CC patients resistant to PTX.
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http://dx.doi.org/10.1002/ddr.21834DOI Listing
May 2021

A 4-W Analog Front End Achieving 2.4 NEF for Long-Term ECG Monitoring.

IEEE Trans Biomed Circuits Syst 2021 May 27;PP. Epub 2021 May 27.

An ultra-low power low noise analog front end (AFE) is presented in this work, aiming for long-term ECG with clear P-waves for clinical diagnose. The proposed AFE achieves a noise-efficient-factor (NEF) of 2.4 and an input-referred noise of 0.39 Vrms in the best case, which shows 3.7X noise improvements among the state-of-the-art designs. The chopper amplifier applies embedded passive high-pass filters to reduce the influence of the offset and noise. With the digital offset cancellation by the pulse-width modulation wave, the AFE achieves a low input-referred dc offset of 0.4 V among 9 tested chips. A 25 dB programmable gain controlled by nano-ampere current bias and the ADC buffer copes with the amplitude variation among patients within small current cost. A closed-loop dynamic scale ADC with low-power comparator logic prevents the instability and signal loss problem, achieving an SFDR of 71.6 dB. The presented AFE consumes 4 W. And the fabricated chip is demonstrated in a miniature prototype for long-term ECG monitoring application and recorded a clear ECG waveform with visible P-wave. The simultaneously ECG recording with a medical grade 12-lead ECG Holter shows the effective acquisition of the prototype, proofing the better noise performance.
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http://dx.doi.org/10.1109/TBCAS.2021.3084152DOI Listing
May 2021

Learning Semantic Segmentation of Large-Scale Point Clouds with Random Sampling.

IEEE Trans Pattern Anal Mach Intell 2021 May 25;PP. Epub 2021 May 25.

We study the problem of efficient semantic segmentation for large-scale 3D point clouds. By relying on expensive sampling techniques or computationally heavy pre/post-processing steps, most existing approaches are only able to be trained and operate over small-scale point clouds. In this paper, we introduce RandLA-Net, an efficient and lightweight neural architecture to directly infer per-point semantics for large-scale point clouds. The key to our approach is to use random point sampling instead of more complex point selection approaches. Although remarkably computation and memory efficient, random sampling can discard key features by chance. To overcome this, we introduce a novel local feature aggregation module to progressively increase the receptive field for each 3D point, thereby effectively preserving geometric details. Comparative experiments show that our RandLA-Net can process 1 million points in a single pass with up to 200X faster than existing approaches. Moreover, extensive experiments on several large-scale point cloud datasets, including Semantic3D, SemanticKITTI, Toronto3D, S3DIS and NPM3D, demonstrate the state-of-the-art semantic segmentation performance of our RandLA-Net.
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http://dx.doi.org/10.1109/TPAMI.2021.3083288DOI Listing
May 2021

Bigu-Style Fasting Affects Metabolic Health by Modulating Taurine, Glucose, and Cholesterol Homeostasis in Healthy Young Adults.

J Nutr 2021 May 12. Epub 2021 May 12.

Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Dynamic orchestration of metabolic pathways during continuous fasting remains unclear.

Objective: We investigated the physiological effects of Bigu-style fasting and underlying metabolic reprogramming in healthy adults.

Methods: We conducted a 5-d Bigu trial in 43 healthy subjects [age 23.2 ± 2.4 y; BMI (in kg/m2) 22.52 ± 1.79]. Physiological indicators and body composition were monitored daily during fasting day 1 (F1D) to F5D and after 10-d refeeding postfasting (R10D) and R30D. Blood samples were collected in the morning. Risk factors associated with inflammation, aging, cardiovascular diseases, malnutrition, and organ dysfunction were evaluated by biochemical measurements. Untargeted plasma metabolomics and gut microbial profiling were performed using plasma and fecal samples. Data were analyzed by repeated measures ANOVA with Greenhouse-Geisser correction. Correlation analyses for metabolite modules and taurine were analyzed by Spearman's rank and Pearson tests, respectively.

Results: Heart rate was accelerated throughout the fasting period. Risk factors associated with inflammation and cardiovascular diseases were significantly lowered during or after Bigu (P < 0.05). Body composition measurement detected an overconsumption of fat starting from F3D till 1 mo after refeeding. Metabolomics unveiled a coupling between gluconeogenesis and cholesterol biosynthesis beyond F3D. Plasma taurine significantly increased at F3D by 31%-46% followed by a reduction to basal level at F5D (P < 0.001), a pattern inversely correlated with changes in glucose and de novo synthesized cholesterol (r = -0.407 and -0.296, respectively; P < 0.001). Gut microbial profiling showed an enrichment of taurine-utilizing bacteria at F5D, which was completely recovered at R10D.

Conclusions: Our data demonstrate that 5-d Bigu is potentially beneficial to health in young adults. A starvation threshold of 3-d fasting is necessary for maintaining glucose and cholesterol homeostasis via a taurine-microbiota regulatory loop. Our findings provide novel insights into the physiological and metabolic responses of the human body to continuous Bigu-style fasting. This trial was registered at http://www.chictr.org.cn as ChiCTR1900022917.
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http://dx.doi.org/10.1093/jn/nxab123DOI Listing
May 2021

Tai Chi exercise improves age-associated decline in cerebrovascular function: a cross-sectional study.

BMC Geriatr 2021 05 6;21(1):293. Epub 2021 May 6.

School of Physical Education, Wuhan Sports University, 430079, Wuhan, China.

Background: Tai Chi exercise has been reported to enhance physical and mental health in the older adults; however, the mechanism remains elusive.

Trial Design: We recruited 289 older adults practicing Tai Chi for over 3 years, together with 277 age-matched older and 102 young adults as controls. 168 Tai Chi practitioners were successfully matched to 168 older controls aged 60-69 based on a propensity score for statistics.

Methods: Cerebrovascular function was evaluated by measuring the hemodynamics of the carotid artery. Spearman correlation was performed to validate the age-associated physiological parameters.

Results: Cerebrovascular function in older adults significantly degenerated compared with the young, and was substantially correlated with age. Compared with the older control group, Tai Chi practitioners showed significant improvements in CVHI (cerebral vascular hemodynamics indices) Score (P = 0.002), mean blood flow velocity (P = 0.014), maximal blood flow velocity (P = 0.04) and minimum blood flow velocity (P < 0.001), whereas the age-related increases in pulse wave velocity (P = 0.022), characteristic impedance (P = 0.021) and peripheral resistance (P = 0.044) were lowered.

Conclusions: These data demonstrate a rejuvenation role of Tai Chi in improving the age-related decline of the cerebrovascular function.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR1900025187).
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http://dx.doi.org/10.1186/s12877-021-02196-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101197PMC
May 2021

A two fluorescent signal indicator-based ratio fluorometric alkaline phosphatase assay based on one signal precursor.

Chem Commun (Camb) 2021 May;57(36):4444-4447

Key Laboratory of Bioelectrochemistry & Environmental Analysis of Gansu Province, College of Chemistry & Chemical Engineering, Northwest Normal University, Lanzhou, 730070, China.

Two fluorescent signal indicators were simply converted from one organic precursor system by using the superior oxidation capability of manganese dioxide (MnO2) nanosheets for the first time, finally resulting in the successful fabrication of a ratio fluorometric bioassay of alkaline phosphatase (ALP).
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http://dx.doi.org/10.1039/d1cc00244aDOI Listing
May 2021

p55PIK deficiency and its NH-terminal derivative inhibit inflammation and emphysema in COPD mouse model.

Am J Physiol Lung Cell Mol Physiol 2021 Jul 5;321(1):L159-L173. Epub 2021 May 5.

Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Chronic obstructive pulmonary disease (COPD) is composed of chronic airway inflammation and emphysema. Recent studies show that Class IA phosphatidylinositol 3-kinases (PI3Ks) play an important role in the regulation of inflammation and emphysema. However, there are few studies on their regulatory subunits. p55PIK is a regulatory subunit of Class IA PI3Ks, and its unique NH-terminal gives it special functions. p55PIK expression in the lungs of nonsmokers, smokers, and patients with COPD was examined. We established a fusion protein TAT-N15 from the NH-terminal effector sequence of p55PIK and TAT (the transduction domain of HIV transactivator protein) and investigated the effects of silencing p55PIK or adding TAT-N15 on cigarette smoke exposure at the cellular and animal level. p55PIK expression was increased in patients with COPD. p55PIK deficiency and TAT-N15 significantly inhibited the cigarette smoke extract-induced IL-6, IL-8, and activation of the Akt and the NF-κB pathway in BEAS-2B. p55PIK deficiency and TAT-N15 intranasal administration prevented emphysema and the lung function decline in mice exposed to smoke for 6 mo. p55PIK deficiency and TAT-N15 significantly inhibited lung inflammatory infiltration, reduced levels of IL-6 and KC in mice lung homogenate, and inhibited activation of the Akt and the NF-κB signaling in COPD mice lungs. Our studies indicate that p55PIK is involved in the pathogenesis of COPD, and its NH-terminal derivative TAT-N15 could be an effective drug in the treatment of COPD by inhibiting the activation of the Akt and the NF-κB pathway.
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http://dx.doi.org/10.1152/ajplung.00560.2020DOI Listing
July 2021

B-cell acute lymphoblastic leukemia-related microRNAs: uncovering their diverse and special roles.

Am J Cancer Res 2021 15;11(4):1104-1120. Epub 2021 Apr 15.

Department of Hematology, The Second Xiangya Hospital, Central South University Changsha, Hunan, China.

B-cell acute lymphoblastic leukemia (B-ALL) is a common type of hematologic malignancy characterized by the uncontrolled growth of immature B lymphocytes. Genomics, transcriptomics, and proteomics at different levels contribute to early diagnosis and can thereby provide better treatment for cancer. MicroRNAs (miRNAs) are conducive to the diagnosis and treatment of patients with B-ALL. Moreover, evidence suggests that runaway miRNAs and exosomes containing miRNA may be involved in the occurrence of B-ALL, which can then be used as potential biomarkers. This review summarizes the role of miRNAs in the pathogenesis, diagnosis, prognosis, and treatment of B-ALL.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085864PMC
April 2021

Crtc1 Deficiency Causes Obesity Potentially via Regulating PPARγ Pathway in White Adipose.

Front Cell Dev Biol 2021 12;9:602529. Epub 2021 Apr 12.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Obesity is characterized by excessive fat accumulation and associated with glucose and lipid metabolism disorders. Crtc1, a transcription cofactor regulating CREB activity, has been involved in the pathogenesis of metabolic syndrome; however, the underlying mechanism remains under debate. Here we generated a Crtc1 mouse line using the CRISPR/Cas9 system. Under normal feeding conditions, Crtc1 mice exhibited an obese phenotype resultant from the abnormal expansion of the white adipocytes. The development of obesity in Crtc1 mice is independent of alterations in food intake or energy expenditure. Moreover, Crtc1 mice were more prone to insulin resistance and dyslipidemia, as evidenced by higher levels of plasma glucose, insulin and FABP4 than wildtype mice. Transcriptome analysis in liver and epididymal white adipose tissue (eWAT) showed that the fat accumulation caused by Crtc1 deletion was mainly related to lipid metabolism in adipose tissue, but not in liver. GSEA and KEGG analysis identified PPAR pathway to be of the highest impact on lipid metabolism in eWAT. This regulation was independent of a direct interaction between CRTC1 and PPARγ. Our findings demonstrate a crucial role of Crtc1 in regulating lipid metabolism in adipose during development, and provide novel insights into obesity prevention and therapeutics.
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http://dx.doi.org/10.3389/fcell.2021.602529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075410PMC
April 2021

Smart biomimetic metal organic frameworks based on ROS-ferroptosis-glycolysis regulation for enhanced tumor chemo-immunotherapy.

J Control Release 2021 06 17;334:21-33. Epub 2021 Apr 17.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:

Antitumor immunotherapy is limited by low tumor immunogenicity and immunosuppressive microenvironment (TIME), which could be improved by "ROS-ferroptosis-glycolysis regulation" strategy. Herein, a cancer cell membrane coated metal organic framework (MOF) loading with glucose oxidase (GOx) and doxorubicin (DOX) was constructed (denoted as mFe(SS)/DG). Benefiting from the homotypic targeting of cancer cell membrane, the nanoplatform effectively accumulated in tumors. mFe(SS)/DG based on coordination between Fe and disulfide-bearing ligand scavenged GSH and downregulated glutathione peroxide 4 (GPX4) to trigger ferroptosis. GOx catalyzed glucose to generate abundant HO for enhancing Fenton reaction, resulting in excessive ROS in tumors. The ROS burst simultaneously promoted ferroptosis and inhibited glycolysis. Ferroptosis combined with DOX induced immunogenic cell death (ICD) and released tumor antigens to initiate antitumor immunity. Glycolysis repression remodeled TIME by decreasing lactate to solidify and boost the antitumor immunity. The smart biomimetic nanoplatform integrates tumor metabolism and immunity based on ROS-ferroptosis-glycolysis regulation, providing a potential anti-tumor strategy.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.013DOI Listing
June 2021

3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry.

Int J Biol Sci 2021 19;17(5):1217-1233. Epub 2021 Mar 19.

Department of Health Care, Zhenjiang Fourth Peoples Hospital, Zhenjiang, China.

3,3'-Diindolylmethane (DIM), a natural phytochemicals isolated from cruciferous vegetables, has been reported to inhibit human gastric cancer cells proliferation and induce cells apoptosis as well as autophagy, but its mechanisms are still unclear. Store-operated calcium entry (SOCE) is a main Ca influx pathway in various of cancers, which is activated by the depletion of endoplasmic reticulum (ER) Ca store. Stromal interaction molecular 1 (STIM1) is the necessary component of SOCE. In this study, we focus on to examine the regulatory mechanism of SOCE on DIM-induced death in gastric cancer. After treating the human BGC-823 and SGC-7901 gastric cancer cells with DIM, cellular proliferation was determined by MTT, apoptosis and autophagy were detected by flow cytometry or Hoechst 33342 staining. The expression levels of related proteins were evaluated by Western blotting. Free cytosolilc Ca level was assessed by fluorescence monitoring under a laser scanning confocal microscope. The data have shown that DIM could significantly inhibit proliferation and induce apoptosis as well as autophagy in two gastric cancer cell lines. After DIM treatment, the STIM1-mediated SOCE was activated by upregulating STIM1 and decreasing ER Ca level. Knockdown STIM1 with siRNA or pharmacological inhibition of SOCE attenuated DIM induced apoptosis and autophagy by inhibiting p-AMPK mediated ER stress pathway. Our data highlighted that the potential of SOCE as a promising target for treating cancers. Developing effective and selective activators targeting STIM1-mediated SOCE pathway will facilitate better therapeutic sensitivity of phytochemicals acting on SOCE in gastric cancer. Moreover, more research should be performed to validate the efficacy of combination chemotherapy of anti-cancer drugs targeting SOCE for clinical application.
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http://dx.doi.org/10.7150/ijbs.56833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040462PMC
March 2021

Synthesis of novel erdite nanorods for the activation of peroxymonosulfate during p-nitrophenol wastewater treatment.

Environ Sci Pollut Res Int 2021 Apr 13. Epub 2021 Apr 13.

Science and Technology Innovation Center for Municipal Wastewater Treatment and Water Quality Protection, Northeast Normal University, Changchun, 130117, China.

Fe-bearing salt and minerals are common reagents used in activating peroxymonosulfate (PMS) for Fenton-like oxidation in wastewater treatment. Fe-bearing reagents are used in mass production, which generate abundant Fe-bearing waste sludge in the absence of a reductant for Fe/Fe cycling. Herein, a novel Fe/S-bearing mineral, erdite, was synthesized with a one-step hydrothermal route. The material exerted an Fe/S synergetic effect for p-nitrophenol degradation upon PMS activation and showed a one-dimensional structure similar to that of (FeS). It contained short rods with diameters of 100 nm and lengths ranging from 200 to 400 nm. It grew radically to 0.8-2 μm in length upon the addition of MnO. Ps-0.5, prepared by adding MnO in an Mn/Fe molar ratio of 0.5, showed optimal efficiency in removing approximately 99.4% of p-nitrophenol upon PMS activation. Only 3.3% of p-nitrophenol was removed without MnO. The efficiency of p-nitrophenol removal through Ps-0.5 activation was higher than that through FeSO, nanoscale zero-valent iron (nZVI), CuFeS, and MnSO activation. The formed erdite rods were spontaneously hydrolyzed to Fe/S-bearing flocs, in which an electron was used by structural S to reduce Fe to Fe upon PMS activation. The reduction resulted in a high p-nitrophenol removal rate. This study provided new insight into the development of an effective PMS activator in wastewater treatment.
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http://dx.doi.org/10.1007/s11356-021-13892-9DOI Listing
April 2021

LncRNA MEG3 Alleviates Diabetic Cognitive Impairments by Reducing Mitochondrial-Derived Apoptosis through Promotion of FUNDC1-Related Mitophagy via Rac1-ROS Axis.

ACS Chem Neurosci 2021 Jul 12;12(13):2280-2307. Epub 2021 Apr 12.

Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China.

Mitochondrial dysfunction and elevated ROS generation are predominant contributors of neuronal death that is responsible for the diabetes-related cognitive impairments. Emerging evidence has demonstrated that long noncoding RNA-MEG3 can serve as an important regulator in the pathogenesis of diabetes. However, the underlying mechanisms remain to be further clarified. Here, it was observed that MEG3 was significantly down-regulated in STZ (streptozotocin)-induced diabetic rats. MEG3 overexpression noticeably improved diabetes-induced cognitive dysfunctions, accompanied by the abatement of Rac1 activation and ROS production, as well as the inhibition of mitochondria-associated apoptosis. Furthermore, either MEG3 overexpression or Rac1 inhibition promoted FUNDC1 dephosphorylation and suppressed oxidative stress and neuro-inflammation. Similarly, studies confirmed that hyperglycemia also down-regulated MEG3 expression in PC12 cells. MEG3 reintroduction protected PC12 cells against hyperglycemia-triggered neurotoxicity by improving mitochondrial fitness and repressing mitochondria-mediated apoptosis. Moreover, these neuroprotective effects of MEG3 relied on FUNDC1-related mitophagy, since silencing of FUNDC1 abolished these beneficial outcomes. Additionally, MEG3 rescued HG-induced neurotoxicity was involved in inhibiting Rac1 expression via interaction with Rac1 3'UTR. Conversely, knockdown of MEG3 showed opposite effects. NSC23766, a specific inhibitor of Rac1, fully abolished harmful effects of MEG3 depletion. Consistently, knockdown of Rac1 potentiated FUNDC1-associated mitophagy. Meanwhile, colocalization of Rac1 and FUNDC1 was found in mitochondria under hyperglycemia, which was interrupted by MEG3 overexpression. Furthermore, silencing of Rac1 promoted PGAM5 expression, and FUNDC1 strongly interacted with LC3 in Rac1-deleted cells. Altogether, our findings suggested that the Rac1/ROS axis may be a downstream signaling pathway for MEG3-induced neuroprotection, which was involved in FUNDC1-associated mitophagy.
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http://dx.doi.org/10.1021/acschemneuro.0c00682DOI Listing
July 2021

Active Fine-Tuning from gMAD Examples Improves Blind Image Quality Assessment.

Authors:
Zhihua Wang Kede Ma

IEEE Trans Pattern Anal Mach Intell 2021 Apr 8;PP. Epub 2021 Apr 8.

The research in image quality assessment (IQA) has a long history, and significant progress has been made by leveraging recent advances in deep neural networks (DNNs). Despite high correlation numbers on existing IQA datasets, DNN-based models may be easily falsified in the group maximum differentiation (gMAD) competition with strong counterexamples being identified. Here we show that gMAD examples can be used to improve blind IQA (BIQA) methods. Specifically, we first pre-train a DNN-based BIQA model using multiple noisy annotators, and fine-tune it on multiple subject-rated databases of synthetically distorted images, resulting in a top-performing baseline model. We then seek pairs of images by comparing the baseline model with a set of full-reference IQA methods in gMAD. We query ground truth quality annotations for the selected images in a well controlled laboratory environment, and further fine-tune the baseline on the combination of human-rated images from gMAD and existing databases. This process may be iterated, enabling active and progressive fine-tuning from gMAD examples for BIQA. We demonstrate the feasibility of our active learning scheme on a large-scale unlabeled image set, and show that the fine-tuned method achieves improved generalizability in gMAD, without destroying performance on previously trained databases.
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http://dx.doi.org/10.1109/TPAMI.2021.3071759DOI Listing
April 2021

Circadian Rhythm Gene PER3 Negatively Regulates Stemness of Prostate Cancer Stem Cells via WNT/β-Catenin Signaling in Tumor Microenvironment.

Front Cell Dev Biol 2021 18;9:656981. Epub 2021 Mar 18.

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

Prostate cancer (PCa) cells are heterogeneous, containing a variety of cancer cells with phenotypical and functional discrepancies in the tumor microenvironment, where prostate cancer stem cells (PCSCs) play a vital role in PCa development. Our earlier studies have shown that ALDHCD44 (DP) PCa cells and the corresponding ALDHCD44 (DN) PCa cells manifest as PCSCs and non-PCSCs, respectively, but the underlying mechanisms regulating stemness of the PCSCs are not completely understood. To tackle this issue, we have performed RNA-Sequencing and bioinformatic analysis in DP (versus DN) cells in this study. We discovered that, PER3 (period circadian regulator 3), a circadian rhythm gene, is significantly downregulated in DP cells. Overexpression of PER3 in DP cells significantly suppressed their sphere- and colony-forming abilities as well as tumorigenicity in immunodeficient hosts. In contrast, knockdown of PER3 in DN cells dramatically promoted their colony-forming and tumor-initiating capacities. Clinically, PER3 is downregulated in human prostate cancer specimens and PER3 expression levels are highly correlated with the prognosis of the PCa patient. Mechanistically, we observed that low levels of PER3 stimulates the expression of BMAL1, leading to the phosphorylation of β-catenin and the activation of the WNT/β-catenin pathway. Together, our results indicate that PER3 negatively regulates stemness of PCSCs via WNT/β-catenin signaling in the tumor microenvironment, providing a novel strategy to treat PCa patients.
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http://dx.doi.org/10.3389/fcell.2021.656981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012816PMC
March 2021

3D DCT Based Image Compression Method for the Medical Endoscopic Application.

Sensors (Basel) 2021 Mar 5;21(5). Epub 2021 Mar 5.

Institute of Microelectronics, Tsinghua University, Beijing 100084, China.

This paper proposes a novel 3D discrete cosine transform (DCT) based image compression method for medical endoscopic applications. Due to the high correlation among color components of wireless capsule endoscopy (WCE) images, the original 2D Bayer data pattern is reconstructed into a new 3D data pattern, and 3D DCT is adopted to compress the 3D data for high compression ratio and high quality. For the low computational complexity of 3D-DCT, an optimized 4-point DCT butterfly structure without multiplication operation is proposed. Due to the unique characteristics of the 3D data pattern, the quantization and zigzag scan are ameliorated. To further improve the visual quality of decompressed images, a frequency-domain filter is proposed to eliminate the blocking artifacts adaptively. Experiments show that our method attains an average compression ratio (CR) of 22.94:1 with the peak signal to noise ratio (PSNR) of 40.73 dB, which outperforms state-of-the-art methods.
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http://dx.doi.org/10.3390/s21051817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961525PMC
March 2021

Optic-fiber vibration sensor based on a reflected 81° tilted fiber grating integrated with a symmetrical flexible hinge.

Appl Opt 2021 Apr;60(10):2886-2892

An optic-fiber vibration sensor based on the reflected 81° tilted fiber grating (81° TFG) integrated with a symmetrical flexible hinge is proposed and experimentally demonstrated in this paper. The vibration sensor is composed of a symmetrical flexible hinge and a reflected 81° TFG, the ends of which are simply fixed on the upper surface of the mass. The theoretical model of the proposed vibration sensor is analyzed, by which the important parameters related to the resonant frequency of the sensor are simulated and discussed; then, the vibration sensing experiments are conducted. Experiment results show that TE/TM mode of the 81° TFG can provide the maximal acceleration sensitivity of 338.28 and 299.94 mV/g at 400 Hz in the flat area of the amplitude-frequency response (50-400 Hz), which is increased by 9.95 and 11.5 times as compared with the optical fiber cantilever beam structure, respectively. Further, the signal-to-noise ratio in the flat area (50-400 Hz) is about ∼66.275 under the acceleration of 2 g, which is increased by ∼20. Furthermore, it can be used for detecting mechanical vibration of medium-high frequency ranging from 50 to 3500 Hz. The proposed 81° TFG vibration sensor has the characteristics of small volume, simple package, high acceleration sensitivity, and wide vibration signal response range, which will ensure it has broad application prospects in the field of mechanical vibration.
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http://dx.doi.org/10.1364/AO.420171DOI Listing
April 2021

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy.

Biomark Res 2021 Mar 31;9(1):23. Epub 2021 Mar 31.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
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http://dx.doi.org/10.1186/s40364-021-00276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011087PMC
March 2021

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer.

Urol Int 2021 Mar 30:1-6. Epub 2021 Mar 30.

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

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety.

Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups.

Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315).

Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.
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http://dx.doi.org/10.1159/000514042DOI Listing
March 2021

EZH2 Dynamically Associates With Non-coding RNAs in Mouse Hearts After Acute Angiotensin II Treatment.

Front Cardiovasc Med 2021 25;8:585691. Epub 2021 Feb 25.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Enhancer of zeste 2 (EZH2) governs gene reprogramming during cardiac hypertrophy through epigenetic remodeling, a process regulated by numerous non-coding RNAs (ncRNAs). However, the dynamic interaction between EZH2 and ncRNAs upon hypertrophic stimulation remains elusive. Here we performed an unbiased profiling for EZH2-associated ncRNAs in mouse hearts treated with Angiotensin II (AngII) at different time points (0, 4, and 24 h). The interactions between EZH2 and long ncRNAs (lncRNAs), Chaer, Mirt1, Hotair, and H19, were validated by PCR. RIP-seq analysis identified a total of 126 ncRNAs to be significantly associated with EZH2. These ncRNAs covers all five categories including intergenic, antisense, intron-related, promoter-related and both antisense and promoter-related. According to their changing patterns after AngII treatment, these ncRNAs were clustered into four groups, constantly enhanced, transiently enhanced, constantly suppressed and transiently suppressed. Structural prediction showed that EZH2 bound to hairpin motifs in ncRNAs including snoRNAs. Interaction strength prediction and RNA pull-down assay confirmed the direct interaction between EZH2 and Snora33. Interestingly, two antisense lncRNAs of Malat1, Gm20417, and Gm37376, displayed different binding patterns from their host gene after AngII treatment, suggesting a crucial role of this genomic locus in modulating EZH2 behavior. Our findings reveal the profile of EZH2-associated ncRNAs upon hypertrophic stimulation, and imply a dynamic regulation of EZH2 function in cardiac hypertrophy.
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http://dx.doi.org/10.3389/fcvm.2021.585691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959742PMC
February 2021

Ferroptosis/pyroptosis dual-inductive combinational anti-cancer therapy achieved by transferrin decorated nanoMOF.

Nanoscale Horiz 2021 04 9;6(4):348-356. Epub 2021 Mar 9.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Non-apoptotic cell death such as ferroptosis and pyroptosis has shed new light on cancer treatment, whereas combinational therapy using both these mechanisms has not yet been fully explored. Herein, a dual-inductive nano-system to realize ferroptosis/pyroptosis mediated anti-cancer effects is presented. The nanodrug ([email protected]) is constructed with a piperlongumine (PL) loaded metal-organic framework (MOF) coated with transferrin decorated pH sensitive lipid layer. Intracellular iron was enriched with an iron-containing MOF, whose endocytosis can be further facilitated by transferrin decorated on the lipid layer, which provides a prerequisite for the occurrence of ferroptosis and pyroptosis. Piperlongumine as the ferroptosis inducer can strengthen the ferroptotic cell death, and provide HO for the dual induction system to increase ROS generation through Fenton reaction. On the basis of validation of both ferroptosis and pyroptosis, the dual-inductive nanodrug demonstrated ideal anticancer effects in the xenograft mice model, which proved that the ferroptosis/pyroptosis dual-inductive nanoplatform could be an effective and promising anticancer modality.
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http://dx.doi.org/10.1039/d0nh00674bDOI Listing
April 2021

A facile calcination conversion of groundwater treatment sludge (GTS) as magnetic adsorbent for oxytetracycline adsorption.

Sci Rep 2021 Mar 5;11(1):5276. Epub 2021 Mar 5.

Science and Technology Innovation Center for Municipal Wastewater Treatment and Water Quality Protection, Northeast Normal University, Changchun, 130117, China.

In this paper, groundwater treatment sludge (GTS) was recycled as a magnetic adsorbent via a facile calcination process without adding any reductant. The prepared magnetic adsorbents (MAs) were characterized by scanning electron microscopy (SEM), X-ray diffractometer (XRD) and X-ray photoelectron spectroscopy (XPS), vibrating sample magnenometer (VSM) and Mössbauer spectroscopy. The results showed that GTS comprised 33.2% Fe, 1.4% Al and 6.2% Si, and exhibited a weak saturation magnetization of 0.0008 emu/g. Without NaOH, the GTS calcinated at 700 and 500 °C were well magnetized with Ms of 20.1 and 7.1 emu/g, separately, but exhibited a low Ms of 0.43 emu/g at 300 °C. By adding NaOH powder, the Ms of GTS apparently increased to 4.9 emu/g after calcination at 300 °C, and further to 8.5 emu/g at 500 °C. In GTS, about 96.1% Fe was involved in ferrihydrite form. The Ms of calcinated GTS was accompanied with the phase transformation of ferrihydrite to maghemite. Si/Al oxides in GTS coordinated on the surface sites of ferrihydrite and inhibited the conjunction and phase transformation of adjacent ferrihydrite particles, but were effectively desorbed as in the presence of NaOH. Na500, preparing by calcinating GTS at 500 °C with NaOH, showed an optimal total surface sites (H) of 0.65 mmol/g. Oxytetracycline (OTC) was used as a target for studying the adsorption characteristics of synthetic magnetic adsorbents and a high adsorption capacity of oxytetracycline of 862.1 mg/g in comparison with the other calcinated GTS, and the adsorption data was consistent with the Langmuir model. By adding 6 g/L Na-500, approximately 100% of oxytetracycline and tetracycline and nearly 40% total organic carbon were removed from real pharmaceutical wastewater. With the method, GTS can be converted in mass production to magnetic adsorbent that exhibits effective application in pharmaceutical wastewater treatment.
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http://dx.doi.org/10.1038/s41598-021-84231-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935931PMC
March 2021

Risk Factors for Mortality of COVID-19 Patient Based on Clinical Course: A Single Center Retrospective Case-Control Study.

Front Immunol 2021 16;12:581469. Epub 2021 Feb 16.

Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Epidemiological factors, clinical characteristics, and risk factors for the mortality of COVID-19 patients have been studied, but the role of complementary systems, possible inflammatory and immune response mechanisms, and detailed clinical courses are uncertain and require further study. In this single center, retrospective case-control study, we included all COVID-19 inpatients transferred or admitted to Wuhan Tongji Hospital from January 3 to March 30 2020 who had definite clinical outcomes (cured or deceased) with complete laboratory and radiological results. Clinical data were extracted from the electronic medical records, and compared between the cured and deceased patients. ROC curves were used to evaluate the prognostic value of the clinical parameters, and multivariable logistic regression analysis was performed to explore the risk factors for mortality. The correlation between the variables was evaluated by Spearman correlation analysis. 208 patients were included in this study, 182 patients were cured and discharged, 26 patients died from COVID-2019. Most patients had comorbidities, with hypertension as the most common chronic disease (80; 38%). The most common symptoms at onset were fever (149; 72%), cough (137; 66%), and dyspnea (113; 54%). Elevated leucocytes, neutrophils, inflammatory biomarkers (CRP, ferritin, IL6, IL8, procalcitonin), PT, D-dimer, myocardial enzymes, BUN, decreased lymphocyte and subsets (T cells, CD4 T cells, CD8 T cells, NK cells, T cells + B cells + NK cells), and immunological factors (C3, C4) indicated poor outcome. PT, C3, and T cells were confirmed as independent prognostic factors for mortality by logistic regression models. IL6 and CPR were positively correlated with neutrophils, but negatively with lymphocytes and lymphocyte subsets except B cells. IL8 and ferritin were negatively related to T cells and CD4 T cells. Positive associations existed between C3 and T cells, CD4 T cells, and CD8 T cells, whereas there was no significant correlation between C4 and lymphocyte subsets. PT was found positively correlated with IL6, IL8, and CRP. Reverse correlations were explored between C3, C4, and PT, CK-MB, total bilirubin. T cells, C3, and PT were identified as independent prognostic factors for mortality. Decreased C3 and C4, dysregulation of lymphocyte subsets and cytokines may lead to death after SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fimmu.2021.581469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920984PMC
March 2021