Publications by authors named "Ying Hou"

197 Publications

Integration of clinicopathologic identification and deep transferrable image feature representation improves predictions of lymph node metastasis in prostate cancer.

EBioMedicine 2021 May 24;68:103395. Epub 2021 May 24.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University; Nanjing, Jiangsu Province, PR China. Electronic address:

Background: Accurate identification of pelvic lymph node metastasis (PLNM) in patients with prostate cancer (PCa) is crucial for determining appropriate treatment options. Here, we built a PLNM-Risk calculator to obtain a precisely informed decision about whether to perform extended pelvic lymph node dissection (ePLND).

Methods: The PLNM-Risk calculator was developed in 280 patients and verified internally in 71 patients and externally in 50 patients by integrating a set of radiologists' interpretations, clinicopathological factors and newly refined imaging indicators from MR images with radiomics machine learning and deep transfer learning algorithms. Its clinical applicability was compared with Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms.

Findings: The PLNM-Risk achieved good diagnostic discrimination with areas under the receiver operating characteristic curve (AUCs) of 0.93 (95% CI, 0.90-0.96), 0.92 (95% CI, 0.84-0.97) and 0.76 (95% CI, 0.62-0.87) in the training/validation, internal test and external test cohorts, respectively. If the number of ePLNDs missed was controlled at < 2%, PLNM-Risk provided both a higher number of ePLNDs spared (PLNM-Risk 59.6% vs MSKCC 44.9% vs Briganti 38.9%) and a lower number of false positives (PLNM-Risk 59.3% vs MSKCC 70.1% and Briganti 72.7%). In follow-up, patients stratified by the PLNM-Risk calculator showed significantly different biochemical recurrence rates after surgery.

Interpretation: The PLNM-Risk calculator offers a noninvasive clinical biomarker to predict PLNM for patients with PCa. It shows improved accuracy of diagnosis support and reduced overtreatment burdens for patients with findings suggestive of PCa.

Funding: This work was supported by the Key Research and Development Program of Jiangsu Province (BE2017756) and the Suzhou Science and Technology Bureau-Science and Technology Demonstration Project (SS201808).
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http://dx.doi.org/10.1016/j.ebiom.2021.103395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167242PMC
May 2021

Anti-HMGCR myopathy overlaps with dermatomyositis-like rash: a distinct subtype of idiopathic inflammatory myopathy.

J Neurol 2021 May 21. Epub 2021 May 21.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, China.

Objective: To characterize the clinical and pathological features of anti-HMGCR myopathy.

Methods: The presence of anti-HMGCR antibody in the serum of 227 patients with idiopathic inflammatory myopathy (IIM) and 100 healthy control individuals was assessed by ELISA. All ELISA positive samples were retested by indirect immunofluorescence assay (IIFA) on HEK293 cells. The clinical findings, muscle pathological features, and treatment outcomes of patients with anti-HMGCR myopathy, along with comparisons between anti-HMGCR myopathy with and without dermatomyositis (DM)-like skin rashes, and among MSA-based subgroups were analyzed.

Results: We established an optimized ELISA cutoff for anti-HMGCR antibody positivity as ≥ 5.28 U. The overall concordance between ELISA and IIFA was 96.83%. Twenty-one out of 227 IIM patients were anti-HMGCR-positive by both assays. Of these 21 patients, 9 had DM-like skin rashes, and 16 showed remarkable muscle inflammation; 5 patients were juvenile-onset, and 2 received statin treatment. The muscle biopsies from these patients demonstrated variable muscle necrosis and T cell infiltration. Most anti-HMGCR-positive patients achieved favorable outcomes following prednisone and additional immunotherapies. The anti-HMGCR myopathy patients with DM-like rashes, compared to those without DM-like rashes, were younger and had a shorter disease duration.

Conclusions: Optimization of cutoff of anti-HMGCR antibody assays with confirmation by alternative assays can result in higher sensitivity and specificity. DM-like skin rashes and lymphocytic infiltrates were not rare in patients with anti-HMGCR myopathy. These findings suggest that while anti-HMGCR myopathy may overlap with DM-like rash, it is pathologically different from classic DM, and should be considered a distinct subgroup of IIM.
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http://dx.doi.org/10.1007/s00415-021-10621-7DOI Listing
May 2021

Artificial intelligence is a promising prospect for the detection of prostate cancer extracapsular extension with mpMRI: a two-center comparative study.

Eur J Nucl Med Mol Imaging 2021 May 21. Epub 2021 May 21.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.

Purpose: A balance between preserving urinary continence as well as sexual potency and achieving negative surgical margins is of clinical relevance while implementary difficulty. Accurate detection of extracapsular extension (ECE) of prostate cancer (PCa) is thus crucial for determining appropriate treatment options. We aimed to develop and validate an artificial intelligence (AI)-based tool for detecting ECE of PCa using multiparametric magnetic resonance imaging (mpMRI).

Methods: Eight hundred and forty nine consecutive PCa patients who underwent mpMRI and prostatectomy without previous radio- or hormonal therapy from two medical centers were retrospectively included. The AI tool was built on a ResNeXt network embedded with a spatial attention map of experts' prior knowledge (PAGNet) from 596 training patients. Model validation was performed in 150 internal and 103 external patients. Performance comparison was made between AI, two experts using a criteria-based ECE grading system, and expert-AI interaction.

Results: An index PAGNet model using a single-slice image yielded the highest areas under the receiver operating characteristic curve (AUC) of 0.857 (95% confidence interval [CI], 0.827-0.884), 0.807 (95% CI, 0.735-0.867), and 0.728 (95% CI, 0.631-0.811) in training, internal, and external validation data, respectively. The performance of two experts (AUC, 0.632 to 0.741 vs 0.715 to 0.857) was lower (paired comparison, all p values < 0.05) than that of AI assessment. When experts' interpretations were adjusted by AI assessments, the performance of two experts was improved.

Conclusion: Our AI tool, showing improved accuracy, offers a promising alternative to human experts for ECE staging using mpMRI.
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http://dx.doi.org/10.1007/s00259-021-05381-5DOI Listing
May 2021

Juvenile idiopathic inflammatory myopathies with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in a Chinese cohort.

CNS Neurosci Ther 2021 May 1. Epub 2021 May 1.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Aims: To characterize the clinical and histopathological characteristics and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIMs) with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies in a Chinese cohort.

Methods: We detected anti-HMGCR antibodies in a series of Chinese JIIM by ELISA and indirect immunofluorescence assay on HEK293 cells, and summarized the clinical findings of these anti-HMGCR antibody-positive patients.

Results: Of 32 JIIM patients, 5 (15.63%) were found to be anti-HMGCR antibody-positive. The disease duration was 1.20 ± 0.45 months. Statin exposure was not found. Four patients had skin lesions, while typical pathological features of dermatomyositis such as perifascicular atrophy or myxovirus resistance protein A expression were not found. The mean creatine kinase level was 16771.60 U/L. Among the four patients who received long-term (10.46 ± 1.42 years) follow-up, three exhibited favorable outcomes with prednisone and additional immunosuppressants.

Conclusions: Our study indicates that anti-HMGCR antibodies may not be rare in Chinese JIIM. These anti-HMGCR-positive JIIMs were characterized by acute onset, substantially elevated creatine kinase level, and skin lesions without perifascicular changes in muscle pathology. The treatment outcome is generally favorable with the combination of steroid and immunosuppressant.
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http://dx.doi.org/10.1111/cns.13658DOI Listing
May 2021

Premature Discontinuation of Dual Antiplatelet Therapy After Coronary Stenting in Veterans: Characteristics and Long-Term Outcomes.

J Am Heart Assoc 2021 May 26;10(9):e018481. Epub 2021 Apr 26.

Veterans Affairs Boston Healthcare System West Roxbury MA.

Background Premature discontinuation of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is related to higher short-term risks of adverse outcomes. Whether these risks persist in the long-term is uncertain. Methods and Results We assessed all patients having percutaneous coronary intervention with coronary second- or first-generation drug-eluting stents in the Veterans Affairs healthcare system between 2006 and 2012 who were free of major ischemic or bleeding events in the first 12 months. The characteristics of patients who stopped DAPT prematurely (1-9 months duration), compared with >9 to 12 months, or extended duration (>12 months) were assessed by odds ratios (ORs) from multivariable logistic models. The risk of adverse clinical outcomes over a mean 5.1 years in patients who stopped DAPT prematurely was assessed by hazard ratios (HRs) and 95% CIs from Cox regression models. A total of 14 239 had second-generation drug-eluting stents, and 8583 had first-generation drug-eluting stents. Premature discontinuation of DAPT was more likely in Black patients (OR, 1.54; 95% CI, 1.40-1.68), patients with greater frailty (OR, 1.04; 95% CI, 1.03-1.05), and patients with higher low-density lipoprotein cholesterol, and less likely in patients on statins (OR, 0.87; 95% CI, 0.80-0.95). Patients who stopped DAPT prematurely had higher long-term risks of death (second-generation drug-eluting stents: HR, 1.35; 95% CI, 1.19-1.56), myocardial infarction (second-generation drug-eluting stents: HR, 1.46; 95% CI, 1.22-1.74), and repeated coronary revascularization (second-generation drug-eluting stents: HR, 1.24; 95% CI, 1.08-1.41). Conclusions Patients who stop DAPT prematurely have features that reflect greater frailty, poorer medication use, and other social factors. They continue to have higher risks of major adverse outcomes over the long-term and may require more intensive surveillance many years after percutaneous coronary intervention.
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http://dx.doi.org/10.1161/JAHA.120.018481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200740PMC
May 2021

Impact of Subthalamic Deep Brain Stimulation on Hyposmia in Patients With Parkinson's Disease Is Influenced by Constipation and Dysbiosis of Microbiota.

Front Neurol 2021 6;12:653833. Epub 2021 Apr 6.

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China.

Non-motor symptoms in PD usually arise at very early stage and vary during the whole disease progression. Deep brain stimulation (DBS) is considered as a highly efficient treatment option for PD's motor function. However, the effect of DBS on NMS, especially hyposmia, has not been fully understood and the deep connection between different NMS such as hyposmia and constipation is still unknown. The objective of this study was to evaluate the therapeutic effect of DBS on hyposmia in PD patients with or without constipation and find potential factors which might influence the efficacy. A retrospective analysis of 65 PD patients accepted STN-DBS operation in Qilu Hospital during 2019-2020 were conducted to evaluate the exact therapeutic effect of DBS on hyposmia in PD. Sub-group analyses about the relationship between hyposmia and constipation were carried out. Analysis of flora in nasal mucosa was also conducted to evaluate the abundance and variety in different PD groups. Our study showed that DBS had clearly improved olfactory function in Parkinson patients ( = 0.012) and subgroup analysis found that PD patients with constipation have lower olfactory function scores (25.27 ± 3.44 vs. 33.90 ± 6.633, = 0.014) and worse improvement after DBS operation (ΔTDI 12.11 ± 3.2 vs. 8.78 ± 2.91, = 0.0072). Analysis of flora indicated the obvious discrepancy on olfactory function scores and degree of improvement might be related to the abundance and dysbiosis of microbiota. In summary, this article presents a study on PD with hyposmia and constipation after DBS operation, explored the relationship between different NMS and offer a potential explanation on why PD patients with constipation usually have worse olfactory function for the less abundance and variety of microbiota.
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http://dx.doi.org/10.3389/fneur.2021.653833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056012PMC
April 2021

Nannocystin Ax, a natural elongation factor 1α inhibitor from Nannocystis sp., suppresses epithelial-mesenchymal transition, adhesion and migration in lung cancer cells.

Toxicol Appl Pharmacol 2021 06 14;420:115535. Epub 2021 Apr 14.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address:

Epithelial-mesenchymal transition (EMT), the epithelial cells transdifferentiation into the mesenchymal cells, has been involved in cancer metastasis. Nannocystin ax (NAN) is a cyclodepsipeptide initially isolated from Myxobacterial genus, Nannocystis sp. with anticancer activities. This study was designed to explore the effect of NAN on TGF-β1-induced EMT in lung cancer cells. The morphological alteration was observed with a microscope. Western blotting and immunofluorescence assays were used to detect the protein expression and the localization. The adhesion and migration were evaluated by adhesion assay and wound healing assay. The mRNA expression of TGF-β receptor type I (TβRI) was determined by real-time PCR. NAN significantly restrained TGF-β1-induced EMT morphological changes, the protein expression of E-cadherin, N-cadherin, and Vimentin, etc. TGF-β1 activated phosphorylation and nuclear translocation of Smad2/3 were inhibited by NAN. Furthermore, NAN suppressed adhesion and migration triggered by TGF-β1. In addition, NAN significantly down-regulated TβRI on the transcriptional level directly. In summary, these results showed that NAN restrained TGF-β1-induced epithelial-mesenchymal transition, migration, and adhesion in human lung cancer cells. The underlying mechanism involved the inhibition of Smad2/3 and the TβRI signaling pathway. This study reveals the new anticancer effect and mechanism of NAN.
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http://dx.doi.org/10.1016/j.taap.2021.115535DOI Listing
June 2021

Geniposide from var. Makino Attenuates Myocardial Injury in Spontaneously Hypertensive Rats via Regulating Apoptotic and Energy Metabolism Signalling Pathway.

Drug Des Devel Ther 2021 3;15:949-962. Epub 2021 Mar 3.

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.

Introduction: Hypertension is closely related to myocardial injury. Long-term hypertension can cause myocardial injury. Therefore, it is very important to find drugs to treat myocardial injury caused by hypertension. The aim of present study is to investigate the effects and mechanisms of geniposide on myocardial injuries in spontaneously hypertensive rats (SHR) and H9c2 cells induced by NaCl solution.

Materials And Methods: Male Wistar-Kyoto (WKY) and SHR rats were given different doses of geniposide (25 mg/kg/d or 50 mg/kg/d) or distilled water for three consecutive weeks. Meanwhile, an H9c2 cell line-injury model was established using a solution of 150 µmol/L NaCl for 8 h. The cardiac function and related indexes of rats were detected.

Results: The results showed that geniposide decreased the levels of COI and COIII, which promoted the phosphorylation of AMPK (p-AMPK) and enhanced the energy metabolism pathway. Geniposide improved myocardial apoptosis by regulating apoptotic proteins (p38, BAX and Bcl-2). Finally, heart function was regulated, and the markers of myocardial injury were decreased. Geniposide increased the viability of H9c2 cells treated with the NaCl solution and decreased the rate of apoptosis by regulating the levels of apoptotic proteins. Geniposide could activate energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and reduce H9c2 cell apoptosis.

Conclusion: Our results showed that the mechanisms by which geniposide improves myocardial injury in SHR may be through regulating the energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and improving myocardial apoptosis by regulating apoptotic proteins.
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http://dx.doi.org/10.2147/DDDT.S292107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937395PMC
March 2021

A novel strategy for glioblastoma treatment by induction of noptosis, an NQO1-dependent necrosis.

Free Radic Biol Med 2021 Apr 15;166:104-115. Epub 2021 Feb 15.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China. Electronic address:

Glioblastoma (GBM) is one of the most prevalent malignant primary tumors in the human brain. Temozolomide (TMZ), the chemotherapeutic drug for GBM treatment, induces apoptosis. Unfortunately, apoptosis-resistance to TMZ results in treatment failure. GBM shows enhanced expression of NAD(P)H: quinone oxidoreductase 1 (NQO1). Recently, noptosis, a type of NQO1-dependent necrosis, was proposed. Here, we identified that tanshindiol B (TSB) inhibits GBM growth by induction of noptosis. TSB triggered significant cell death, which did not fit the criteria of apoptosis but oxidative stress-induced necrosis. Molecular docking, cellular thermal shift assay, and NQO1 activity assay revealed that TSB bind to and promptly activated NQO1 enzyme activity. As the substrate of NQO1, TSB induced oxidative stress, which resulted in dramatic DNA damage, poly (ADP-ribose) polymerase 1 (PARP1) hyperactivation, and NAD depletion, leading to necrotic cell death. These effects of TSB were completely abolished by specific NQO1 inhibitor dicoumarol (DIC). Furthermore, the c-Jun N-terminal kinase 1/2 (JNK1/2) plays an essential role in mediating TSB-induced cell death. Besides, TSB significantly suppressed tumor growth in a zebrafish xenograft model mediated by NQO1. In conclusion, these results showed that TSB was an NQO1 substrate and triggered noptosis of GBM. TSB exhibited anti-tumor potentials in GBM both in vitro and in vivo. This study provides a novel strategy for fighting GBM through the induction of noptosis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.014DOI Listing
April 2021

Bioactive Limonoids and Triterpenoids from the Fruits of .

J Nat Prod 2020 12 30;83(12):3502-3510. Epub 2020 Nov 30.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.

Nine new limonoids, meliazedarines A-I (-), seven known analogues (-), and five known triterpenoids (-) were isolated from the fruits of . Their structures were determined by analysis of 1D and 2D NMR, HRESIMS, X-ray diffraction, and electronic circular dichroism (ECD) data. Compound showed significant cytotoxicity against the HCT116 cell line with IC values of 0.3 ± 0.1 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.9b01151DOI Listing
December 2020

Taxifolin improves disorders of glucose metabolism and water-salt metabolism in kidney via PI3K/AKT signaling pathway in metabolic syndrome rats.

Life Sci 2020 Dec 4;263:118713. Epub 2020 Nov 4.

Henan University of Chinese Medicine, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou 450046, China. Electronic address:

Aims: Our study was designed to explore the function and mechanism of taxifolin on glucose metabolism and water-salt metabolism in kidney with metabolic syndrome (MS) rats.

Main Methods: Spontaneous hypertensive rats were induced by fructose to establish MS model. Systolic blood pressure (SBP) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured after 7 weeks of continuous administration with taxifolin. Kidney injury indices and histopathological evaluation were done. The apoptosis rate of primary kidney cells was detected by flow cytometry. Insulin signaling pathway related proteins and renal glucose transport-related proteins were detected by western blotting. We assessed the effects of taxifolin on sodium water retention and renin-angiotensin-aldosterone system (RAAS) in MS rats. We examined not only changes in urine volume, osmotic pressure, urinary sodium and urinary chloride excretion, but also the effects on NA/K-ATPase and RAAS indicators. We also detected changes in inflammatory factors by immunohistochemical staining and immunofluorescence. In vitro experiment, high glucose and salt stimulated NRK-52E cells. By adding the PI3K inhibitor (wortmannin) to inhibit the PI3K, the effects of inhibiting the PI3K/AKT signaling pathway on glucose metabolism, water-sodium retention and inflammatory response were discussed.

Key Findings: Taxifolin effectively reversed SBP, HOMA-IR, the kidney indices and abnormal histopathological changes induced by MS. Besides, taxifolin called back the protein associated with the downstream glucose metabolism pathway of PI3K/AKT. It also inhibited overactivation of RAAS and inflammatory response. In vitro experiments have demonstrated that the PI3K/AKT signaling pathway plays an important role in this process.

Significance: Taxifolin can improve homeostasis of glucose, inhibit overactivation of RAAS and reduce inflammatory response by PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1016/j.lfs.2020.118713DOI Listing
December 2020

Optimized MRI Assessment for Clinically Significant Prostate Cancer: A STARD-Compliant Two-Center Study.

J Magn Reson Imaging 2021 04 19;53(4):1210-1219. Epub 2020 Oct 19.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: There is a requirement for a personalized strategy to make MRI more accessible to men with suspicion of clinically significant prostate cancer (CSPC).

Purpose: To evaluate an optimized (Op)-MRI compared with biparametric (Bp)-MRI and multiparametric (Mp)-MRI for the diagnosis of CSPC.

Study Type: Two-center, retrospective.

Subjects: A total of 346 patients from center 1 and 292 patients from center 2.

Field Strength/sequence: 3.0T scanners, T -weighted imaging (T WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging.

Assessment: Four radiologists interpreted the Bp-MRI (T WI and DWI) and Mp-MRI (T WI, DWI, and DCE) independently according to the Prostate Imaging Reporting and Data System (PI-RADS). For Op-MRI, two radiologists used an adjusted decision rule on Bp-MRI-assessed PI-RADS 3 lesions by determining early enhancement of DCE. Pathologies at biopsy and/or prostatectomy specimens were used as standard references.

Statistical Tests: Performance was assessed using receiver operating characteristic (ROC) curves. Kappa statistics were used to assess interobserver variability.

Results: Interreader agreement was excellent for all three MRI assessments (all κ values >0.80). Op-MRI had comparable sensitivity (senior/junior: 90.9% [261/287] / 91.6% [263/287]) and higher specificity (78.1% [274/351] /74.4% [261/351]) compared with Mp-MRI (sensitivity: 92.3% [265/287] / 93.7% [269/287]; specificity: 67.8% [238/351] / 68.1% [239/351]) and Bp-MRI (sensitivity: 91.6% [263/287] / 93.4% [268/287]; specificity: 71.2% [250/351] / 70.1% [246/351]) for the diagnosis of CSPC. Compared to Mp-MRI, Op-MRI spared biopsy in 80.7% (515/638) of DCE scans with similar performance accuracy. Compared to Bp-MRI, Op-MRI downgraded 25.2% (31/123) of lesions at a cost of missing 6.5% (3/46) of malignancies, and upgraded 45.5% (56/123) of lesions with a positive predictive value of 62.5% (35/56) in 123 equivocal findings.

Data Conclusion: The Op-MRI, using an adjusted PI-RADS decision rule, did not compromise diagnostic accuracy with sparing biopsy in 80.7% of DCE scans compared to Mp-MRI, and outperformed Bp-MRI by regrading PI-RADS lesions.

Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27394DOI Listing
April 2021

Hollow Mesoporous Carbon Sphere Loaded Ni-N Single-Atom: Support Structure Study for CO Electrocatalytic Reduction Catalyst.

Small 2020 Oct 6;16(41):e2003943. Epub 2020 Sep 6.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China.

Single-atom catalysts have become a hot spot because of the high atom utilization efficiency and excellent activity. However, the effect of the support structure in the single-atom catalyst is often unnoticed in the catalytic process. Herein, a series of carbon spheres supported Ni-N single-atom catalysts with different support structures are successfully synthesized by the fine adjustment of synthetic conditions. The hollow mesoporous carbon spheres supported Ni-N catalyst (Ni/HMCS-3-800) exhibits superior catalytic activity toward the electrocatalytic CO reduction reaction (CO RR). The Faradaic efficiency toward CO is high to 95% at the potential range from -0.7 to -1.1 V versus reversible hydrogen electrode and the turnover frequency value is high up to 15 608 h . More importantly, the effect of the geometrical structures of carbon support on the CO RR performance is studied intensively. The shell thickness and compactness of carbon spheres regulate the chemical environment of the doped-N species in the carbon skeleton effectively and promote CO molecule activation. Additionally, the optimized mesopore size is beneficial to improve diffusion and overflow of the substance, which enhances the CO adsorption capacity greatly. This work provides a new consideration for promoting the catalytic performance of single-atom catalysts.
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http://dx.doi.org/10.1002/smll.202003943DOI Listing
October 2020

Acacetin improves endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats by estrogen receptors.

Mol Biol Rep 2020 Sep 6;47(9):6899-6918. Epub 2020 Sep 6.

Henan University of Chinese Medicine, Zhengzhou, 450046, China.

The aim of the work was to investigate the effects of acacetin on endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats and explore its mechanism. Seven-week-old male spontaneously hypertensive rats (SHR) were selected to establish a rat model of hypertension with insulin resistance induced by 10% fructose. The nuclear factor kappa B p65 (NF-κB p65) and Collagen I were observed by Immunohistochemistry. Immunofluorescence was used to observe estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30). Western blotting was used to detect interleukin (IL-1β), Arginase 2 (ARG2), Nostrin, endothelial nitric oxide synthase (eNOS), TGF-β, Smad3, ERK pathway proteins such as p-c-Raf, p-MEK1/2, p-ERK, ERK, p-P90RSK and p-MSK1. We found that acacetin did have an improvement on endothelial dysfunction and fibrosis. Meanwhile, it was also found to have a significant effect on the level of estrogen in this model by accident. Then, the experiment of uterine weight gain in mice confirmed that acacetin had a certain estrogen-like effect in vivo and played its role through the estrogen receptors pathway. In vitro experience HUVEC cells were stimulated with 30 mM/L glucose and 100 mM/L NaCl for 24 h to establish the endothelial cell injury model. HUVEC cells were treated with 1 μM/L estrogen receptors antagonist (ICI 182780) for 30 min before administration. Cell experiments showed that acacetin could reduce the apoptosis of HUVEC cells, the levels of inflammatory cytokines and the expression of TGF-β, Collagen I and Smad3 in endothelial cell injury model. After treatment with ICI 182780, the improvement of acacetin was significantly reversed. The results showed that acacetin relieved endothelial dysfunction and reduced the aortic fibrosis in insulin-resistant SHR rats by reducing the release of inflammatory factors and improving vasodilatory function through estrogen signaling pathway.
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http://dx.doi.org/10.1007/s11033-020-05746-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561596PMC
September 2020

HSPB8 overexpression prevents disruption of blood-brain barrier after intracerebral hemorrhage in rats through Akt/GSK3β/β-catenin signaling pathway.

Aging (Albany NY) 2020 Sep 4;12(17):17568-17581. Epub 2020 Sep 4.

Department of Neurology, 2nd Xiangya Hospital, Central South University Changsha, Hunan Province, China.

Blood brain barrier (BBB) disruption is a crucial factor contributing to secondary brain injury after intracerebral hemorrhage (ICH). Heat shock protein B8 (HSPB8) has been recently reported to confer neuroprotection against against ischaemic stroke through maintaining BBB integrity. However, the role of HSPB8 in ICH is still elusive. In this study, we found that HSPB8 was upregulated by ICH and extensively expressed in neurovascular structure including endothelial cells and astrocytes. lentivirus intracerebroventricular () injection achieved a widespread and persistent HSPB8 overexpression in brain tissues. HSPB8 overexpression significantly ameliorated neurobehavioral deficits and brain edema at 24 and 72h following ICH. Moreover, HSPB8 overexpression remarkedly inhibited BBB disruption and significantly increase the level of p-Akt, p-GSKβ and intranuclear β-catenin 24h post-ICH. This effect was obviously reversed by Akt specific inhibitor, MK2206. Based on these findings, HSPB8 exerted its protective effect on BBB, at least partly, via Akt/ p-GSKβ/β-catenin pathways.
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http://dx.doi.org/10.18632/aging.103773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521513PMC
September 2020

Geniposide in Gardenia jasminoides var. radicans Makino modulates blood pressure via inhibiting WNK pathway mediated by the estrogen receptors.

J Pharm Pharmacol 2020 Dec 24;72(12):1956-1969. Epub 2020 Aug 24.

Henan University of Chinese Medicine, Zhengzhou, Henan, China.

Objectives: To investigate the effects of geniposide in an iridoid found in Gardenia jasminoides var. radicans Makino (GJRM) in spontaneous hypertensive rat (SHR) and explore the possible mechanisms.

Methods: In this study, we detected the content of geniposide in GJRM by high-performance liquid chromatography (HPLC). Then, we used acute diuretic experiments to determine whether geniposide has diuretic effect. Moreover, we carried out experiments on SHR to further study the mechanism of hypertension, while real-time PCR, Western blot and immunohistochemistry were used for the experiments in vivo test. Hypotonic model was used for in vitro test.

Key Findings: Our data showed that the content of geniposide in the extract of GJRM is 27.54%. Meanwhile, 50 mg/kg geniposide showed the strongest effect on promoting urine volume. Further study indicated that the extract of GJRM and geniposide could significantly reduce blood pressure and promote the excretion of urine and Na in SHR. In addition, geniposide significantly inhibited the activation of the with-no-lysine kinase (WNK) signalling pathway and significantly increases the protein expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ) and G protein-coupled receptor 30 (GPR30) in SHR. In hypotonic model, geniposide significantly inhibits the phosphorylation of NKCC and NCC and could be antagonistic to estrogen receptor antagonists.

Conclusions: Collectively, we would suggest that geniposide may potentially be utilized as an adjunct to existing thiazide and thiazide-like diuretics to control hypertension, mainly through inhibiting the activation of the WNK signalling pathway mediated by the estrogen receptor.
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http://dx.doi.org/10.1111/jphp.13361DOI Listing
December 2020

Ecosystem service potential, flow, demand and their spatial associations: a comparison of the nutrient retention service between a human- and a nature-dominated watershed.

Sci Total Environ 2020 Dec 2;748:141341. Epub 2020 Aug 2.

Institute for Natural Resource Conservation, Department of Ecosystem Management, Kiel University, Kiel, Germany.

Nutrient regulation is an important ecosystem regulating service in watersheds. However, systematic investigations of the spatial associations between the potential, flow, and demand of the nutrient regulation service are still lacking. Therefore, we performed a case study comparing the total phosphorus (TP) retention in the Dianchi Lake (DL) watershed (human-dominated) with that in the Lower Reach of the Zi River (LRZR) watershed (nature-dominated). We used four indicators-TP retention potential, TP retention, TP load, and TP export-to represent the potential, flow, demand, and flow-demand budget of the TP retention service, respectively. We estimated the TP retention and export using the InVEST tool, mapped the four TP indicators and calculated their correlations, and estimated the contributions of different ecosystem types and terrain ranges to TP retention and export. We determined the following: (1) the incongruity between the spatial distribution of the TP retention potential and the other three TP indicators was smaller in the LRZR watershed than in the DL watershed; (2) the TP retention potentials generally increased-while the other three TP indicators decreased-with increases in the elevation gradient in the DL watershed and the slope gradients in both study areas; and (3) paddy fields exhibited the highest TP retention intensity and residential areas exhibited the highest TP export intensity among the major ecosystem types in both study areas. Moreover, the TP retention intensities of dryland crops and residential areas in the DL watershed were much higher than they were in the LRZR watershed. Our findings imply that the flow of the nutrient retention service is influenced more by the service demand than by the service potential and that it is influenced by both landscape composition and pattern. Because of the limitations and uncertainties in the modeling outputs, our results should be carefully used in other studies or in decision-making.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141341DOI Listing
December 2020

FeAture Explorer (FAE): A tool for developing and comparing radiomics models.

PLoS One 2020 17;15(8):e0237587. Epub 2020 Aug 17.

Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, China.

In radiomics studies, researchers usually need to develop a supervised machine learning model to map image features onto the clinical conclusion. A classical machine learning pipeline consists of several steps, including normalization, feature selection, and classification. It is often tedious to find an optimal pipeline with appropriate combinations. We designed an open-source software package named FeAture Explorer (FAE). It was programmed with Python and used NumPy, pandas, and scikit-learning modules. FAE can be used to extract image features, preprocess the feature matrix, develop different models automatically, and evaluate them with common clinical statistics. FAE features a user-friendly graphical user interface that can be used by radiologists and researchers to build many different pipelines, and to compare their results visually. To prove the effectiveness of FAE, we developed a candidate model to classify the clinical-significant prostate cancer (CS PCa) and non-CS PCa using the PROSTATEx dataset. We used FAE to try out different combinations of feature selectors and classifiers, compare the area under the receiver operating characteristic curve of different models on the validation dataset, and evaluate the model using independent test data. The final model with the analysis of variance as the feature selector and linear discriminate analysis as the classifier was selected and evaluated conveniently by FAE. The area under the receiver operating characteristic curve on the training, validation, and test dataset achieved results of 0.838, 0.814, and 0.824, respectively. FAE allows researchers to build radiomics models and evaluate them using an independent testing dataset. It also provides easy model comparison and result visualization. We believe FAE can be a convenient tool for radiomics studies and other medical studies involving supervised machine learning.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237587PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431107PMC
October 2020

Natural alkaloid 8-oxo-epiberberine inhibited TGF-β1-triggred epithelial-mesenchymal transition by interfering Smad3.

Toxicol Appl Pharmacol 2020 10 1;404:115179. Epub 2020 Aug 1.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address:

Epithelial-mesenchymal transition (EMT), the transition of epithelial cells into mesenchymal cells, plays important roles in the metastasis of solid tumors. 8-Oxo-epiberberine (OPB) is a natural alkaloid extracted from the roots of Coptis chinensis Franch. In this study, The effect and the underlying mechanism of OPB on EMT in a TGF-β1-induced model and the inhibitory effect of OPB on lung metastasis were investigated. TGF-β1-stimulated lung cancer cells were co-treated with OPB, the morphological changes were examined. The protein expression of EMT biomarkers E-cadherin and N-cadherin was determined by Western blotting and immunofluorescence. The transcription activity of smad2/3 promoter was analyzed by a luciferase reporter assay. The effect of OPB on cell migration, invasion, and adhesion was detected by wound-healing, adhesion, and transwell assays. The in vivo anti-metastatic effect of OPB was evaluated using a 4 T1 cell xenograft mouse model. Results showed that OPB significantly reversed TGF-β1-triggered morphological changes, expression of EMT biomarkers, and migration, adhesion, and invasion. Furthermore, OPB suppressed TGF-β1-induced Smad2/3 activation, Smad3 phosphorylation and nuclear translocation, and interaction of Smad3 with Smad4. Besides, OPB dramatically decreased the metastatic nodules in the lung without affecting the growth of primary tumors. In conclusion, OPB inhibited TGF-β1-induced EMT possibly by interfering with Smad3. OPB might have therapeutic potentials for the treatment of metastatic cancers.
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http://dx.doi.org/10.1016/j.taap.2020.115179DOI Listing
October 2020

A radiomics machine learning-based redefining score robustly identifies clinically significant prostate cancer in equivocal PI-RADS score 3 lesions.

Abdom Radiol (NY) 2020 12 1;45(12):4223-4234. Epub 2020 Aug 1.

Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210009, Jiangsu Province, China.

Purpose: PI-RADS score 3 is recognized as equivocal likelihood of clinically significant prostate cancer (csPCa) occurrence. We aimed to develop a Radiomics machine learning (RML)-based redefining score to screen out csPCa in equivocal PI-RADS score 3 category.

Methods: Total of 263 patients with the dominant index lesion scored PI-RADS 3 who underwent biopsy and/or follow-up formed the primary cohort. One-step RML (RML-i) model integrated radiomic features of T2WI, DWI, and ADC images all together, and two-step RML (RML-ii) model integrated the three independent radiomic signatures from T2WI (T2WI), DWI (DWI), and ADC (ADC) separately into a regression model. The two RML models, as well as T2WI, DWI, and ADC, were compared using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analysis (DCA). Two radiologists were asked to give a subjective binary assessment, and Cohen's kappa statistics were calculated.

Results: A total of 59/263 (22.4%) csPCa were identified. Inter-reader agreement was moderate (Kappa = 0.435). The AUC of RML-i (0.89; 95% CI 0.88-0.90) is higher (p = 0.003) than that of RML-ii (0.87; 95% CI 0.86-0.88). The DCA demonstrated that the RML-i and RML-ii significantly improved risk prediction at threshold probabilities of csPCa at 20% to 80% compared with doing-none or doing-all by PI-RADS score 3 or stratifying by separated DWI, ADC, or T2WI.

Conclusion: Our RML models have the potential to predict csPCa in PI-RADS score 3 lesions, thus can inform the decision making process of biopsy.
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http://dx.doi.org/10.1007/s00261-020-02678-1DOI Listing
December 2020

Elderly patients with hypertension self-perceived of aging status and compliance with medical behaviour.

Psychol Health Med 2020 Jul 31:1-13. Epub 2020 Jul 31.

Nursing Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

At present, it is rare for studies to be performed on the impact of self-perceptions of aging on the compliance behaviour of elderly people.The present study explored the relationship between self-perceived of aging level and compliance behavior among asample of elderly Chinese hypertension patients. Participants (N=1129) were recruited from four community health service centres and two township hospitals in Suzhou. Self-perceptions of aging represent an independent risk factor for compliance behaviour in elderly patients with hypertension. Self-perceptions of aging had acute/chronic timeliness (OR=0.793), periodic timeliness (OR=1.439), emotional representation (OR=0.735), positive results (OR=1.322), and identity latitude (OR=0.995). Gender (OR=1.390), age (OR=1.982), residence (OR=7.037), hypertension grade (OR=0.598), sleep (OR=1.709), number of hospital admissions in a year (OR=2.757), number of daily uses of antihypertensive drugs (OR=0.338), and frequency of blood pressure measurement (OR=0.387) were independent factors affecting the compliance behavior of elderly patients with hypertension. The results suggest that self-perceptions of aging can be used as an indirect index to monitor the compliance behaviour of the elderly. In the future medical staff should combine the characteristics of the elderly patients with hypertension, which would help them to establish a positive self-perception of aging, thus improving their compliance behaviour, and the levels of health and literacy.
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http://dx.doi.org/10.1080/13548506.2020.1800056DOI Listing
July 2020

Effect of phenylacetamide isolated from on myocardial injury in spontaneously hypertensive rats and its possible mechanism.

Pharm Biol 2020 Dec;58(1):597-609

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.

In the antihypertensive study of phenylacetamide (PA) on spontaneously hypertensive rats (SHR), it was occasionally found that PA prevents myocardial injury. Clarify the protective mechanism of PA on myocardial injury in SHR rats., SHR rats were treated with or without PA (15, 30, 45 mg/kg) for 3 weeks (12 per group). , H9c2 cells were treated with PA (1, 5, 10 μM) for 24 h, and then stimulated with HO (300 μM) for 4 h. Molecular mechanisms were explored through cardiac pathology, cardiac function and biochemical markers., PA (15, 30, 45 mg/kg) reduced CVF from 14.8 ± 1.62 to 9.94 ± 1.56, 8.6 ± 1.33, 8.14 ± 1.45%; increased the LVEF relative level from 0.8 ± 0.06 to 0.83 ± 0.04, 0.86 ± 0.05, 0.9 ± 0.04. All three doses can improve the cardiac pathological structure and function (LVEDD, LVESD, LVFS, heart index, NT-proBNP, CKMB, SBP); however, 45 mg/kg works best. But different doses show different molecular mechanisms. PA (15 mg/kg) improves RAAS system (REN, ACE), inflammation (ET-1, IL-1β) and MAPK pathway (p-ERK/ERK, p-JNK/JNK) better. PA (45 mg/kg) improves oxidative stress (SOD, NOX1) and TGF-β pathway (Smad3) better. , PA improved cell viability, oxidative stress (SOD, NOX1) and Smad3 protein expression. PA regulates different mechanisms at different concentrations to improve myocardial injury, and high dose is the best. This experiment provides a theoretical basis for the development of new clinical drugs for cardiovascular disease.
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http://dx.doi.org/10.1080/13880209.2020.1778043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470167PMC
December 2020

Yes-associated protein and transcriptional coactivator with PDZ-binding motif as new targets in cardiovascular diseases.

Pharmacol Res 2020 09 15;159:105009. Epub 2020 Jun 15.

Institute of Basic and Translational Medicine, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China; School of Basic and Medical Sciences, Xi'an Medical University, Xi'an, Shaanxi 710021, China. Electronic address:

As transcriptional co-activators, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) can regulate cell proliferation, migration, differentiation, and apoptosis by interacting with the transcription factors [e.g., transcriptional enhancer associate domain (TEAD) family members]. Polarity and junctional proteins, mechanical stress, and G protein-coupled receptors (GPCRs) are Hippo pathway-dependent upstream regulatory pathways of YAP and TAZ activity. In addition, posttranslational modifications (such as phosphorylation, O-GlcNAcylation, acetylation, methylation, geranylgeranylation, and palmitoylation) also participate in the regulation of YAP and TAZ activity. YAP and TAZ have recently been implicated in the pathological process of vascular and heart diseases. The activation of YAP and TAZ promotes atherosclerosis, angiogenesis, restenosis, pulmonary hypertension, myocardial hypertrophy, and myocardial fibrosis, whereas the inhibition of YAP and TAZ is involved in aortic aneurysms, aortic dissection, myocardial ischemia-reperfusion injury, and myocardial infarction. Thus, both YAP and TAZ may be potential targets for treating cardiovascular diseases. In this review, we discuss the latest findings regarding YAP and TAZ and the potential drugs that target these compounds to treat cardiovascular diseases. This review lays the foundation for a future direction of cardiovascular disease research.
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http://dx.doi.org/10.1016/j.phrs.2020.105009DOI Listing
September 2020

Induction of programmed necrosis: A novel anti-cancer strategy for natural compounds.

Pharmacol Ther 2020 10 31;214:107593. Epub 2020 May 31.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address:

Cell death plays a critical role in organism development and the pathogenesis of diseases. Necrosis is considered a non-programmed cell death in an extreme environment. Recent advances have provided solid evidence that necrosis could be programmed and quite a few types of programmed necrosis, such as necroptosis, ferroptosis, pyroptosis, paraptosis, mitochondrial permeability transition-driven necrosis, and oncosis, have been identified. The specific biomarkers, detailed signaling, and precise pathophysiological importance of programmed necrosis are yet to be clarified, but these forms of necrosis provide novel strategies for the treatment of various diseases, including cancer. Natural compounds are a unique source of lead compounds for the discovery of anti-cancer drugs. Natural compounds can induce both apoptosis and programmed necrosis. In this review, we summarized the recent progress of programmed necrosis and introduced their natural inducers. Noptosis, which is a novel type of programmed necrosis that is strictly dependent on NAD(P)H: quinone oxidoreductase 1-derived oxidative stress was proposed. Furthermore, the anti-cancer strategies that take advantage of programmed necrosis and the main concerns from the scientific community in this regard were discussed.
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http://dx.doi.org/10.1016/j.pharmthera.2020.107593DOI Listing
October 2020

Adoption of image surface parameters under moving edge computing in the construction of mountain fire warning method.

PLoS One 2020 27;15(5):e0232433. Epub 2020 May 27.

The Second Monitoring and Application Center, CEA, Xi an, China.

In order to cope with the problems of high frequency and multiple causes of mountain fires, it is very important to adopt appropriate technologies to monitor and warn mountain fires through a few surface parameters. At the same time, the existing mobile terminal equipment is insufficient in image processing and storage capacity, and the energy consumption is high in the data transmission process, which requires calculation unloading. For this circumstance, first, a hierarchical discriminant analysis algorithm based on image feature extraction is introduced, and the image acquisition software in the mobile edge computing environment in the android system is designed and installed. Based on the remote sensing data, the land surface parameters of mountain fire are obtained, and the application of image recognition optimization algorithm in the mobile edge computing (MEC) environment is realized to solve the problem of transmission delay caused by traditional mobile cloud computing (MCC). Then, according to the forest fire sensitivity index, a forest fire early warning model based on MEC is designed. Finally, the image recognition response time and bandwidth consumption of the algorithm are studied, and the occurrence probability of mountain fire in Muli county, Liangshan prefecture, Sichuan is predicted. The results show that, compared with the MCC architecture, the algorithm presented in this study has shorter recognition and response time to different images in WiFi network environment; compared with MCC, MEC architecture can identify close users and transmit less data, which can effectively reduce the bandwidth pressure of the network. In most areas of Muli county, Liangshan prefecture, the probability of mountain fire is relatively low, the probability of mountain fire caused by non-surface environment is about 8 times that of the surface environment, and the influence of non-surface environment in the period of high incidence of mountain fire is lower than that in the period of low incidence. In conclusion, the surface parameters of MEC can be used to effectively predict the mountain fire and provide preventive measures in time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232433PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252597PMC
July 2020

Pseudoginsenoside-F11 ameliorates ischemic neuron injury by regulating the polarization of neutrophils and macrophages in vitro.

Int Immunopharmacol 2020 Aug 21;85:106564. Epub 2020 May 21.

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, PR China. Electronic address:

Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has neuroprotective effects on permanent and transient cerebral ischemia in rats by alleviating autophagic/lysosomal defects and repressing calcium overload, respectively. Ischemic stroke triggers peripheral innate immune cells, mainly neutrophils and macrophages, to infiltrate the damaged brain. The polarization of neutrophils and macrophages after cerebral ischemia is essential for post-stroke damage/recovery. However, it remains elusive whether PF11 ameliorates ischemic neuron injury by regulating the polarization of neutrophils and macrophages. The present study demonstrated for the first time that conditioned media from ischemic neurons induced neutrophils and macrophages to polarize into N1 and M1 phenotypes, respectively. Furthermore, PF11 (30, 100 μM) inhibited the induction of N1 neutrophils by conditioned media from oxygen glucosedeprivation/re-oxygenation (OGD/R)-induced ischemic neurons and promoted the polarization of neutrophils to N2 phenotypes. In addition, PF11 (100 μM) attenuated the exacerbation of N1 neutrophils and facilitated the protection of N2 neutrophils on OGD/R-induced neuronal damage. Similarly, PF11 (100 μM) inhibited the induction of M1 macrophages by conditioned media from ischemic neurons and facilitated the polarization of macrophages to M2 phenotypes. What's more, PF11 (100 μM) attenuated the aggravation of M1 macrophages and promoted the protection of M2 macrophages on OGD/R-induced primary neuron injury. In summary, the present study indicates that PF11 ameliorates ischemic neuron damage by regulating neutrophils and macrophages polarization, suggesting that neutrophils and macrophages may be promising targets for the treatment of cerebral ischemia.
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http://dx.doi.org/10.1016/j.intimp.2020.106564DOI Listing
August 2020

Using Ecosystem Service Flows to Inform Ecological Compensation: Theory & Application.

Int J Environ Res Public Health 2020 05 11;17(9). Epub 2020 May 11.

State Key Laboratory of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Ecological compensation is a crucial policy instrument that realigns the benefits of stakeholders to the ecosystem service provision. However, the spatial disconnections between locations where ecosystem services produced and used are common. The supply and demand for ecosystem services are calculated to reflect the status of the districts or counties based on ecosystem service flows. The replacement cost methods provide necessary technical supports for the calculation of compensation funds. The realigning of compensation funds between service-benefiting areas and service-providing areas not only identifies the beneficiaries and suppliers but also realizes the connection between them, which may be a feasible methodology. Fuzhou City is the study area, and two ecosystem services of water conservation and soil retention were taken into consideration. The prioritized development zone, Linchuan, and the key agricultural production zones paid ecological compensation funds. Linchuan paid the highest, 5.76 billion yuan. The key ecological function zones and the key agricultural production zones received the ecological compensation funds, of which Yihuang obtained the highest, 1.66 billion yuan. The realigning of compensation funds between the service benefiting and providing areas addresses the trade-offs between ecosystem services, social development, and ecosystem protection. Embedding the ecosystem service flows into the ecological compensation mechanism can most truly realize the value of ecosystem services, achieve the "beneficiary pays" principle, and be conducive to regional sustainable development.
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http://dx.doi.org/10.3390/ijerph17093340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246574PMC
May 2020

Ag(I)-Hived Fullerene Microcube as an Enhanced Catalytic Substrate for the Reduction of 4-Nitrophenol and the Photodegradation of Orange G Dye.

Langmuir 2020 May 11;36(19):5236-5242. Epub 2020 May 11.

Department of Chemistry and Material Science, South-Central University of Nationalities, Wuhan 430074, P. R. China.

We report a facile approach to fabricate an Ag-embedded fullerene (C) catalyst by the chemical reduction of the AgNO complex encapsulated fullerene microcrystal, which showed an enhanced catalytic reduction of 4-nitrophenol because of the strong absorption and propagation of H along the fullerene surface. With the aid of visible-light radiation, photodegradation of orange G dye is achieved through the formation of an electron donor-acceptor dyad between plasmon Ag nanostructures and fullerene molecules, which effectively offsets the "electron-hole" recombination. Neither Ag nanoparticle nor fullerene crystal used in isolation could perform this chemical conversion, implying that the metal-fullerene hybrid structure is imperative for performing the catalytic reaction. The obtained Ag-embedded fullerene crystal is characterized by scanning electron microscopy (SEM), associated energy-dispersive X-ray spectroscopy (EDX) imaging, and X-ray photoelectron spectroscopy (XPS) and demonstrates that the present hybrid materials would add a supplemental member to a family of photocatalysts toward the organic synthesis and wastewater remediation.
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http://dx.doi.org/10.1021/acs.langmuir.0c00580DOI Listing
May 2020

Gasdermine E-Dependent Mitochondrial Pyroptotic Pathway in Dermatomyositis: A Possible Mechanism of Perifascicular Atrophy.

J Neuropathol Exp Neurol 2020 05;79(5):551-561

Department of Neurology, Qilu Hospital (Qingdao), Qingdao, Shandong, China.

Different mechanisms have been proposed to explain the pathological basis of perifascicular atrophy (PFA), a pathognomonic histologic feature of dermatomyositis (DM); however, the detailed mechanisms remain to be elucidated. There is mitochondrial dysfunction in PFA and expression of mitochondrial apoptosis molecules has been reported in DM. Overexpression of gasdermin E (GSDME) can turn mitochondrial apoptosis to mitochondrial pyroptosis, a newly characterized form of programmed cell death. We determined the expression of proteins involved in the caspase-3- and GSDME-dependent mitochondrial pyroptotic pathway, including BAX, BAK, cytochrome C, caspase-9, caspase-3, GSDME, and IL-1α, in biopsied muscles from DM and control patients. Immunohistochemical analysis showed that those markers were expressed in most fibers in PFA in DM. GSDME-positive and IL-1α-positive staining was mainly localized around punched-out vacuoles or sarcolemma. These markers were significantly upregulated at the protein and mRNA levels in DM versus controls. Our results suggest that caspase-3- and GSDME-dependent mitochondrial pyroptosis are involved in the pathogenetic mechanisms of PFA in DM and that targeting GSDME-dependent mitochondrial pyroptosis may be an effective therapeutic approach for this condition.
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http://dx.doi.org/10.1093/jnen/nlaa023DOI Listing
May 2020

2-Methoxy-6-acetyl-7-methyljuglone (MAM) induced programmed necrosis in glioblastoma by targeting NAD(P)H: Quinone oxidoreductase 1 (NQO1).

Free Radic Biol Med 2020 05 28;152:336-347. Epub 2020 Mar 28.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China. Electronic address:

Glioblastoma (GBM) are the most malignant brain tumors in humans and have a very poor prognosis. Temozolomide (TMZ), the only chemotherapeutic drug for GBM treatment, induced apoptosis but frequently developed resistance. Non-apoptotic cell death offers an alternative strategy to fight cancers. Our previous studies showed that 2-methoxy-6-acetyl-7-methyljuglone (MAM), a natural product, induced necroptosis in lung and colon cancer cells. The current study is designed to investigate its therapeutic potentials for GBM with in vitro and in vivo models. The protein expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) in human GBM specimens were detected by immunohistochemistry. Effect of MAM on NQO1 was measured by recombinant protein and cellular thermal shift assay. The roles of NQO1 activation, superoxide (O) generation, calcium (Ca) accumulation, and c-Jun N-terminal kinase (JNK1/2) activation in MAM-induced cell death in U87 and U251 glioma cells were investigated. The effect of MAM on tumor growth was tested with a U251 tumor xenograft zebrafish model. Results showed that the NQO1 expression is positively correlated with the degree of malignancy in GBM tissues. MAM could directly bind and activate NQO1. Furthermore, MAM treatment induced rapid O generation, cytosolic Ca accumulation, and sustained JNK1/2 activation. In addition, MAM significantly suppressed tumor growth in the zebrafish model. In conclusion, MAM induced GBM cell death by triggering an O/Ca/JNK1/2 dependent programmed necrosis. NQO1 might be the potential target for MAM and mediated its anticancer effect. This non-apoptotic necrosis might have therapeutic potentials for GBM treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.03.026DOI Listing
May 2020