Publications by authors named "Shun Zhang"

335 Publications

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis.

Int J Mol Sci 2021 Sep 23;22(19). Epub 2021 Sep 23.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of , have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.
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http://dx.doi.org/10.3390/ijms221910229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508562PMC
September 2021

N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties.

Eur J Med Chem 2021 Sep 24;226:113859. Epub 2021 Sep 24.

Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. Electronic address:

Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.
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http://dx.doi.org/10.1016/j.ejmech.2021.113859DOI Listing
September 2021

Oncolytic adenoviruses synergistically enhance anti-PD-L1 and anti-CTLA-4 immunotherapy by modulating the tumour microenvironment in a 4T1 orthotopic mouse model.

Cancer Gene Ther 2021 Sep 24. Epub 2021 Sep 24.

Department of Experimental Haematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.

Effective therapeutic strategies for triple-negative breast cancer (TNBC) are still lacking. Clinical data suggest that a large number of TNBC patients cannot benefit from single immune checkpoint inhibitor (ICI) treatment due to the immunosuppressive tumour microenvironment (TME). Therefore, combination immunotherapy is an alternative approach to overcome this limitation. In this article, we combined two kinds of oncolytic adenoviruses with ICIs to treat TNBC in an orthotopic mouse model. Histopathological analysis and immunohistochemistry as well as multiplex immunofluorescence were used to analyse the TME. The immunophenotype of the peripheral blood and spleen was detected by using flow cytometry. Oncolytic adenovirus-mediated immune activity in a coculture system of lytic supernatant and splenocytes supported the study of the mechanism of combination therapy in vitro. Our results showed that the combination of oncolytic adenoviruses with anti-programmed cell death-ligand 1 (anti-PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (anti-CTLA-4) (aPC) can significantly inhibit tumour growth and prolong survival in a TNBC model. The combination therapy synergistically enhanced the antitumour effect by recruiting CD8 T and T memory cells, reducing the number of regulatory T cells and tumour-associated macrophages, and promoting the polarization of macrophages from the M2 to the M1 phenotype to regulate the TME. The rAd.GM regimen performed better than the rAd.Null treatment. Furthermore, aPC efficiently blocked oncolytic virus-induced upregulation of PD-L1 and CTLA-4. These findings indicate that oncolytic adenoviruses can reprogramme the immunosuppressive TME, while ICIs can prevent immune escape after oncolytic virus therapy by reducing the expression of immune checkpoint molecules. Our results provide a mutually reinforcing strategy for clinical combination immunotherapy.
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http://dx.doi.org/10.1038/s41417-021-00389-3DOI Listing
September 2021

Brain oxygen extraction fraction mapping in patients with multiple sclerosis.

J Cereb Blood Flow Metab 2021 Sep 24:271678X211048031. Epub 2021 Sep 24.

Department of Radiology, Weill Cornell Medicine, New York, NY, USA.

We aimed to demonstrate the feasibility of whole brain oxygen extraction fraction (OEF) mapping for measuring lesion specific and regional OEF abnormalities in multiple sclerosis (MS) patients. In 22 MS patients and 11 healthy controls (HC), OEF and neural tissue susceptibility () maps were computed from MRI multi-echo gradient echo data. In MS patients, 80 chronic active lesions with hyperintense rim on quantitative susceptibility mapping were identified, and the mean OEF and within the rim and core were compared using linear mixed-effect model analysis. The rim showed higher OEF and than the core: relative to their adjacent normal appearing white matter, OEF contrast = -6.6 ± 7.0% vs. -9.8 ± 7.8% (p < 0.001) and contrast = 33.9 ± 20.3 ppb vs. 25.7 ± 20.5 ppb (p = 0.017). Between MS and HC, OEF and were compared using a linear regression model in subject-based regions of interest. In the whole brain, compared to HC, MS had lower OEF, 30.4 ± 3.3% vs. 21.4 ± 4.4% (p < 0.001), and higher , -23.7 ± 7.0 ppb vs. -11.3 ± 7.7 ppb (p = 0.018). Our feasibility study suggests that OEF may serve as a useful quantitative marker of tissue oxygen utilization in MS.
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http://dx.doi.org/10.1177/0271678X211048031DOI Listing
September 2021

Abnormalities of Cortical Morphology and Structural Covariance Network in Patients with Subacute Basal Ganglia Stroke.

Acad Radiol 2021 Sep 20. Epub 2021 Sep 20.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China. Electronic address:

Rationale And Objectives: The direct damage caused by ischemic stroke is relatively localized, but structural reorganization of cortical regions could occur across the brain. Changes of large-scale, cortical structural brain networks after basal ganglia stroke are less well reported. We, therefore, aim to explore the abnormalities of cortical morphology and structural network topology in patients with unilateral basal ganglia stroke during the subacute period.

Materials And Methods: Thirty patients with first-ever basal ganglia stroke and thirty age- and sex-matched healthy controls were recruited for our analysis. Patients underwent structural magnetic resonance imaging examinations and clinical assessment from seven days to three months post-stroke. Alterations in cortical morphology and topological properties of the cortical structural network were measured respectively using the surface-based morphology and graph-theoretical methods.

Results: We observed focal cortical atrophy, specifically in areas of frontal and temporal cortices. Moreover, the cortical thickness in the contralesional transverse temporal gyrus and superior temporal gyrus was positively correlated with cognitive function scores. Network analysis revealed that patients with basal ganglia stroke showed increased clustering coefficient, increased mean local efficiency as well as a reorganization of degree-based hubs. In addition, these patients also showed reduced robustness under a random attack compared to healthy controls.

Conclusion: These findings indicated a unique pattern of cortical reorganization and the abnormal topological organization of cortical thickness-based structural covariance networks in patients with basal ganglia stroke, which is beneficial to understand the pathophysiological mechanisms of functional disorders at the cortical structural network level and find potential targets for induced neuromodulation.
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http://dx.doi.org/10.1016/j.acra.2021.08.011DOI Listing
September 2021

T2-FLAIR, DWI and DKI radiomics satisfactorily predicts histological grade and Ki-67 proliferation index in gliomas.

Am J Transl Res 2021 15;13(8):9182-9194. Epub 2021 Aug 15.

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

Objective: To build highly predictive performance models for glioma stratification with radiomics features from non-invasive MRI.

Methods: T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) imaging, diffusion-weighted MRI and diffusion kurtosis imaging were retrospectively collected for 139 glioma cases (2 with grade I, 67 with grade II, 36 with grade III and 34 with grade IV disease). Multi-parameter maps, including the apparent diffusion coefficient (ADC), mean diffusion coefficient (Dmean), fractional anisotropy (FA), and mean kurtosis (MK), were co-registered to T2-FLAIR, and 431 radiomics features for each were extracted within manually segmented tumour regions. Partial correlation analysis revealed correlations between radiomics features and glioma stratification factors (tumour grades and Ki-67 LI). Predictive models were built with adjusted-imbalanced logistic regression.

Results: MK radiomics features were more closely correlated with glioma stratification than other modalities analysed. The maximum R in MK was 0.52 for tumour grade and 0.56 for Ki-67 index (compared with 0.36 and 0.34 in FA, and 0.43 and 0.37 in ADC, and 0.48 and 0.42 in T2-FLAIR). The best predictive models for grade II vs. III, grade II vs. IV, low-grade vs. high-grade gliomas and positive vs. highly positive Ki-67 LI were obtained by combining multi-parameter MR radiomics features with AUCs of 0.858, 0.966, 0.853 and 0.870, respectively. However, for grade III vs. IV gliomas, the model obtained from MK radiomics features achieved the highest AUC (0.947), with excellent sensitivity and specificity.

Conclusion: Compared with the other modalities, MK showed closer correlations with tumour grade and Ki-67 LI. Combined radiomics models integrating multi-parameter MRI allow for the generation of highly predictive models for glioma stratification.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430185PMC
August 2021

Gadolinium chloride pre-treatment reduces the inflammatory response and preserves intestinal barrier function in a rat model of sepsis.

Exp Ther Med 2021 Oct 9;22(4):1143. Epub 2021 Aug 9.

Department of Pathophysiology, Shihezi University School of Medicine, The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi, Xinjiang 832002, P.R. China.

The inflammatory response is closely associated with sepsis occurrence and progression. Damage to the function of the intestinal mucosal barrier is considered to be the ῾initiation factor᾿ for the development of multiple organ dysfunction syndrome, which is the most severe progression of sepsis. The aim of the present study was to investigate whether gadolinium chloride (GdCl) could alleviate the systemic inflammatory response and protect the function of the intestinal mucosal barrier in a rat model of sepsis. The mechanism underlying this protective effect was also explored. Sprague-Dawley rats were divided into four groups: Sham, sham + GdCl, cecal ligation and puncture (CLP; a model of sepsis) and CLP + GdCl. In each group, blood was collected from the abdominal aorta, and intestinal tissue was collected after 6, 12 and 24 h of successful modeling. Levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were determined using ELISA. Western blot analysis was used to determine levels of occludin, tight junction protein ZO-1 (ZO-1), myosin light chain kinase 3 (MLCK), NF-κB and caspase-3 in intestinal tissues. Hematoxylin-eosin staining was used to observe the degree of damage to intestinal tissue. The results indicated that in CLP sepsis model rats treated with GdCl, the release of systemic and intestinal pro-inflammatory factors was reduced and tissue damage was alleviated when compared with untreated CLP rats. Additionally, the expression of occludin and ZO-1 was increased, while that of NF-κB, MLCK, and caspase-3 was reduced in the CLP + GdCl rats compared with the CLP rats. GdCl may alleviate systemic and intestinal inflammatory responses and reduce the expression of MLCK through inhibition of the activation of NF-kB. The results of the present study also indicated that GdCl promoted the expression of occludin and ZO-1. GdCl was also demonstrated to reduce cell apoptosis through the inhibition of caspase-3 expression.
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http://dx.doi.org/10.3892/etm.2021.10577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393272PMC
October 2021

TRIM22 inhibits the proliferation of gastric cancer cells through the Smad2 protein.

Cell Death Discov 2021 Sep 7;7(1):234. Epub 2021 Sep 7.

Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.

TRIM22 is involved in tumorigenesis and development, but its mechanism is not clear. In this study, we investigated the expression and biological role of TRIM22 in gastric cancer. We found that TRIM22 mRNA and protein expression was abnormally low in gastric cancer tissues and cells and correlated with tumor size and depth of invasion. Overexpression of TRIM22 significantly inhibited the proliferation, colony formation, and migration of gastric cancer cells and downregulated the expression of HSPA6. However, the HSPA6-siRNA complementation test showed that TRIM22 did not regulate cell proliferation through HSPA6. Furthermore, overexpression of TRIM22 downregulated the phosphorylation of Smad2 and Smad3. In addition, TRIM22 directly binds to Smad2, and overexpression of Smad2 can reverse the inhibition of cell proliferation and migration induced by TRIM22. In vivo, overexpression of TRIM22 significantly inhibited the growth of subcutaneous xenografts in nude mice. Our study indicates that TRIM22 has an important role in the development of gastric cancer and may inhibit the proliferation of gastric cancer cells through Smad2.
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http://dx.doi.org/10.1038/s41420-021-00627-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421354PMC
September 2021

Tractometry-Based Estimation of Corticospinal Tract Injury to Assess Initial Impairment and Predict Functional Outcomes in Ischemic Stroke Patients.

J Magn Reson Imaging 2021 Sep 6. Epub 2021 Sep 6.

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

Background: Corticospinal tract (CST) injury has been shown to exert a major influence on functional recovery after ischemic stroke.

Purpose: To evaluate the prognostic value of CST injury estimated using a recent developed tractometry-based method.

Study Type: Prospective.

Population: Forty-eight patients with CST damage induced by stroke lesion who underwent brain magnetic resonance imaging within 7 days from onset.

Sequence: Diffusion-weighted imaging (b = 1000 seconds/mm ) and diffusion kurtosis imaging (DKI) spin-echo echo-planar sequence with three b-values (0, 1250, and 2500 seconds/mm ) at 3.0 T.

Assessment: A recently developed approach that combines tract segmentation and orientation mapping was used for CST-specific tractography and tractometry. CST injury was estimated using the proposed method with diffusion metrics extracted from DKI sequence and with the first principal component (PC1) of the metrics. We also calculated the weighted lesion load (wLL) for comparison. Clinical evaluation included the National Institutes of Health Stroke Score in the acute phase and the modified Rankin scale at 3 months post-stroke. The correlations between CST injury and initial motor impairment, as well as the prognostic values of CST injury for functional outcomes were evaluated.

Statistical Tests: Pearson correlation and logistic regression. Area under the receiver operating characteristic curve. P < 0.05 was considered statistically significant.

Results: CST injury calculated with diffusion metrics except fractional anisotropy all showed significant correlations with initial motor impairment. PC1 achieved the largest correlation coefficient (R = 0.65) compared with wLL and other diffusion metrics. In addition to wLL, DKI_AK, AFD_total, and PC1 maximum all showed predictive values for functional outcomes.

Data Conclusion: Structural injury to CST is important for the assessment of the extent of injury and the prediction of functional outcome. The method proposed in our study could provide an imaging indicator to quantify the CST injury after ischemic stroke.

Level Of Evidence: 2 TECHNICAL EFFICACY: Stage 1.
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http://dx.doi.org/10.1002/jmri.27911DOI Listing
September 2021

The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke.

Front Neurosci 2021 16;15:716031. Epub 2021 Aug 16.

Department of Radiology, Weill Cornell Medicine, New York, NY, United States.

Purpose: This study aimed to assess the spatiotemporal evolution of oxygen extraction fraction (OEF) in ischemic stroke with a newly developed cluster analysis of time evolution (CAT) for a combined quantitative susceptibility mapping and quantitative blood oxygen level-dependent model (QSM + qBOLD, QQ).

Method: One hundred and fifteen patients in different ischemic stroke phases were retrospectively collected for measurement of OEF of the infarcted area defined on diffusion-weighted imaging (DWI). Clinical severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Of the 115 patients, 11 underwent two longitudinal MRI scans, namely, three-dimensional (3D) multi-echo gradient recalled echo (mGRE) and 3D pseudo-continuous arterial spin labeling (pCASL), to evaluate the reversal region (RR) of the initial diffusion lesion (IDL) that did not overlap with the final infarct (FI). The temporal evolution of OEF and the cerebral blood flow (CBF) in the IDL, the RR, and the FI were assessed.

Results: Compared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases ( < 0.05) and showed a declining tendency from the acute to the chronic phase ( = 0.022). Five of the 11 patients with longitudinal scans showed reversal of the IDL. Relative oxygen extraction fraction (rOEF, compared to the contralateral mirror area) of the RR increased from the first to the second MRI ( = 0.044). CBF was about 1.5-fold higher in the IDL than in the contralateral mirror area in the first MRI. Two patients showed penumbra according to the enlarged FI volume. The rOEF of the penumbra fluctuated around 1.0 at earlier scan times and then decreased, while the CBF decreased continuously.

Conclusion: The spatiotemporal evolution of OEF and perfusion in ischemic lesions is heterogeneous, and the CAT-based QQ method is feasible to capture cerebral oxygen metabolic information.
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http://dx.doi.org/10.3389/fnins.2021.716031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415351PMC
August 2021

Inhibiting Focal Adhesion Kinase Ameliorates Cyst Development in Polycystin-1-Deficient Polycystic Kidney Disease in Animal Model.

J Am Soc Nephrol 2021 Sep;32(9):2159-2174

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous cysts originating from renal tubules and is associated with significant tubular epithelial cell proliferation. Focal adhesion kinase (FAK) promotes tumor growth by regulating multiple proliferative pathways.

Methods: We established the forskolin (FSK)-induced three-dimensional (3D) Madin-Darby Canine Kidney cystogenesis model and 8-bromoadenosine-3`,5`-cyclic monophosphate-stimulated cyst formation in embryonic kidney culture. Cultured human renal cyst-lining cells (OX-161) and normal tubular epithelial cells were treated with FAK inhibitors or transfected with green fluorescent protein-tagged FAK mutant plasmids for proliferation study. Furthermore, we examined the role of FAK in two transgenic ADPKD animal models, the kidney-specific knockout and the collecting duct-specific knockout mouse models.

Results: FAK activity was significantly elevated in OX-161 cells and in two ADPKD mouse models. Inhibiting FAK activity reduced cell proliferation in OX-161 cells and prevented cyst growth in and 3D cyst models. In tissue-specific knockout mouse models, FAK inhibitors retarded cyst development and mitigated renal function decline. Mechanically, FSK stimulated FAK activation in tubular epithelial cells, which was blocked by a protein kinase A (PKA) inhibitor. Inhibition of FAK activation by inhibitors or transfected cells with mutant FAK constructs interrupted FSK-mediated Src activation and upregulation of ERK and mTOR pathways.

Conclusions: Our study demonstrates the critical involvement of FAK in renal cyst development, suggests that FAK is a potential therapeutic target in treating patients with ADPKD, and highlights the role of FAK in cAMP-PKA-regulated proliferation.
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http://dx.doi.org/10.1681/ASN.2020111560DOI Listing
September 2021

Differences in Wall Shear Stress Between High-Risk and Low-Risk Plaques in Patients With Moderate Carotid Artery Stenosis: A 4D Flow MRI Study.

Front Neurosci 2021 11;15:678358. Epub 2021 Aug 11.

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

This study aimed to evaluate the difference in wall shear stress (WSS) (axial, circumferential, and 3D) between high-risk and low-risk plaques in patients with moderate carotid artery stenosis and to identify which time points and directions play the dominant roles in determining the risk associated with plaques. Forty carotid arteries in 30 patients were examined in this study. All patients underwent high-resolution vessel wall (HRVW) imaging, diffusion-weighted imaging (DWI), and 4D flow MRI; HRVW imaging and DWI were used to separate low- and high-risk plaque. Twenty-four high-risk plaques and 16 low-risk plaques were enrolled. An independent-sample -test was used to compare WSS between low- and high-risk plaques in the whole cardiac cycle and at 20 different time points in the cardiac cycle. The study found that patients with high-risk plaques had higher WSS than those with low-risk plaques throughout the entire cardiac cycle ( < 0.05), but the changes varied at the 20 different time points. The number of non-significant differences ( > 0.05) was less in diastole than in systole across different time points. The axial WSS values were higher than the circumferential WSS values; the difference in axial WSS values between high- and low-risk plaques was more significant than the difference in circumferential WSS, whereas 3D WSS values best reflected the difference between high-risk and low-risk plaques because they showed significant differences at every time point. In conclusion, increased WSS, especially during the diastolic period and in the axial direction, may be a signal of a high-risk plaque and may cause cerebrovascular events in patients with moderate carotid artery stenosis. Additionally, WSS can provide hemodynamic information and help clinicians make more appropriate decisions for patients with plaques.
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http://dx.doi.org/10.3389/fnins.2021.678358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385133PMC
August 2021

Effect of Mechanical Heterogeneity on Strain and Stress Fields at Crack Tips of SCC in Dissimilar Metal Welded Joints.

Materials (Basel) 2021 Aug 9;14(16). Epub 2021 Aug 9.

School of Mechanical Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.

The crack tip strain and stress condition are one of the main factors affecting stress corrosion cracking (SCC) behaviors in the dissimilar metal welded joint of the primary circuit in the pressurized water reactor. The mechanical property mismatch of base metal and weld metal can significantly affect the stress and strain condition around the crack tip. To understand the effect of different weld metals on strain and stress fields at SCC crack tips, the effects of strength mismatch, work hardening mismatch, and their synergy on the strain and stress field of SCC in the bi-material interface, including plastic zone, stress state, and corresponding -integral, are investigated in small-scale yielding using the finite element method. The results show a significant effect of the strength mismatch and work hardening mismatch on the plastic zone and stress state in the weld metal and a negligible effect in the base metal. -integral decreases with the single increase in either strength mismatch or work hardening mismatch. Either the increase in strength mismatch or work hardening mismatch will inhibit the other's effect on the -integral, and a synthetic mismatch factor can express this synergistic effect.
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http://dx.doi.org/10.3390/ma14164450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399991PMC
August 2021

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection.

J Clin Lab Anal 2021 Sep 13;35(9):e23923. Epub 2021 Aug 13.

Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Background: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19.

Methods: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors.

Results: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding.

Conclusions: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.
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http://dx.doi.org/10.1002/jcla.23923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418473PMC
September 2021

Extract From Leaf Alleviates Lung Infection: Network Pharmacology Analysis and Experimental Evidence.

Front Pharmacol 2021 19;12:587850. Epub 2021 Jul 19.

Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Diels & Gilg () has attracted much attention due to its ability on pneumonia, bronchitis, and immune-related diseases, while its functional components and underlying mechanism of action on pneumonia have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the action mechanism of leaf in the treatment of pneumonia. In this study, the results of network pharmacology demonstrated that there were 34 active components and 80 drug-disease targets in leaf, which were strongly in connection with signal transduction, inflammatory response, and the oxidation-reduction process. Subsequently, a mouse model of pneumonia induced by () was established to validate the predicted results of network pharmacology. In the animal experiments, aqueous extract of leaf (EFT) significantly attenuated the histopathological changes of lung tissue in -induced mice and reduced the number of bacterial colonies in BALFs by 96.84% ( 0.01). Moreover, EFT treatment suppressed the increase of pro-inflammatory cytokines IL-17, IL-6, and TNF-α in lung tissues triggered by , which led to the increase of Th17 cells ( 0.05). High concentration of EFT treatment (2.0 g/kg) obviously increased the anti-inflammatory cytokine levels, accompanied by the enhancement of Treg proportion in a dose-dependent manner and a notable reversal of transcription factor RORγt expression. These findings demonstrated that network pharmacology was a useful tool for TCM research, and the anti-inflammatory effect of EFT was achieved by maintaining Th17/Treg immune homeostasis and thereby suppressing the inflammatory immune response.
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http://dx.doi.org/10.3389/fphar.2021.587850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326761PMC
July 2021

A robust vasculogenic microfluidic model using human immortalized endothelial cells and Thy1 positive fibroblasts.

Biomaterials 2021 09 16;276:121032. Epub 2021 Jul 16.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. Electronic address:

Human umbilical vein endothelial cells (HUVECs) and stromal cells, such as human lung fibroblasts (FBs), have been widely used to generate functional microvascular networks (μVNs) in vitro. However, primary cells derived from different donors have batch-to-batch variations and limited lifespans when cultured in vitro, which hampers the reproducibility of μVN formation. Here, we immortalize HUVECs and FBs by exogenously expressing human telomerase reverse transcriptase (hTERT) to obtain stable endothelial cell and FB sources for μVN formation in vitro. Interestingly, we find that immortalized HUVECs can only form functional μVNs with immortalized FBs from earlier passages but not from later passages. Mechanistically, we show that Thy1 expression decreases in FBs from later passages. Compared to Thy1 negative FBs, Thy1 positive FBs express higher IGFBP2, IGFBP7, and SPARC, which are important for angiogenesis and lumen formation during vasculogenesis in 3D. Moreover, Thy1 negative FBs physically block microvessel openings, reducing the perfusability of μVNs. Finally, by culturing immortalized FBs on gelatin-coated surfaces in serum-free medium, we are able to maintain the majority of Thy1 positive immortalized FBs to support perfusable μVN formation. Overall, we establish stable cell sources for μVN formation and characterize the functions of Thy1 positive and negative FBs in vasculogenesis in vitro.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121032DOI Listing
September 2021

The complete mitochondrial genome of Chinese minnow () and its phylogenetic analyses.

Mitochondrial DNA B Resour 2021 5;6(8):2177-2179. Epub 2021 Jul 5.

School of Marine Science, Ningbo University, Ningbo, China.

The complete mitochondrial genome can provide novel insights into understanding the mechanism underlying mitogenome evolution. In the present study, the whole mitochondrial genome of was determined to 16608 bp (GenBank accession No: MW057563), including 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region. The overall base composition was 28.62% A, 27.23% T, 26.31% C and 17.84% G, with a total A + T content of 55.85%. The Maximum Likelihood tree showed that the phylogenetic relationship is closer between and than the other species. The whole mitogenome of this species will be useful for the future animal evolutionary, phylogenetic relationship, and genomic studies in the genus .
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http://dx.doi.org/10.1080/23802359.2021.1875921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266249PMC
July 2021

Impacts of PBDE-47 exposure before, during and after pregnancy on the maternal gut microbiome and its association with host metabolism.

Ecotoxicol Environ Saf 2021 Oct 17;222:112530. Epub 2021 Jul 17.

Department of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, China. Electronic address:

Maternal gut microbiota play an important role in the modulation of offspring disease susceptibility and gut microbiota dysbiosis has been proposed as a mechanism through which toxic environmental chemicals exert their adverse impacts on health. The brominated flame retardants polybrominated diphenyl ethers (PBDEs) are developmental toxicants and induce dysbiotic gut microbiota in offspring. Yet, whether and how PBDEs impact the maternal gut microbiota remain unclear. Here, we sought to investigate the effect of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) exposure from preconception through lactation cessation on maternal gut microbiota and its link to host serum metabolic consequences. Female Sprague-Dawley rats were daily exposed to 10 mg/kg PBDE-47 via oral gavage from ten days before conception until offspring were weaned on postnatal day 21, then maternal fecal and blood samples were collected for microbiome and metabolome analyses by using 16S ribosomal RNA gene sequencing and gas chromatography-mass spectrometry, respectively. Maternal exposure to PBDE-47 showed a distinct profile in gut microbiota compared to control dams, as evidenced by increased Actinobacteria phylum and genera Blautia, Gemella and Phascolarctobacterium, and decreased genera AF12 and Oscillospira. Additionally, global metabolomics analysis identified 26 differential serum metabolites to distinguish PBDE-47 from controls, which were mainly involved in amino acid, lipid, carbohydrate and energy metabolism, further confirmed by pathway analysis. Importantly, the differential serum metabolites are closely correlated with the disturbed gut microbiota in response to PBDE-47. Collectively, our results suggest that maternal gut microbial dysbiosis may serve as a potential mechanism underlying PBDE-47-elicited health hazards to mothers or even offspring.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112530DOI Listing
October 2021

Rapid immunoassay and clinical evaluation of the SARS-CoV-2 antibody assay on the real express-6 analyzer.

J Med Virol 2021 12 29;93(12):6544-6550. Epub 2021 Jul 29.

Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

We developed a rapid and simple magnetic chemiluminescence enzyme immunoassay on the Real Express-6 analyzer, which could simultaneously detect immunoglobulin G and immunoglobulin M antibodies against SARS-CoV-2 virus in human blood within 18 min, and which could be used to detect clinical studies to verify its clinical efficacy. We selected blood samples from 185 COVID-19 patients confirmed by polymerase chain reaction and 271 negative patients to determine the clinical detection sensitivity, specificity, stability, and precision of this method. Meanwhile, we also surveyed the dynamic variance of viral antibodies during SARS-CoV-2 infection. This rapid immunoassay test has huge potential benefits for rapid screening of SARS-CoV-2 infection and may help clinical drug and vaccine development.
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http://dx.doi.org/10.1002/jmv.27201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426859PMC
December 2021

miRNA-6715-5p Inhibits Cellular Proliferation and Invasion in Colorectal Cancer by Directly Targeting CST4.

J Oncol 2021 29;2021:7615712. Epub 2021 May 29.

Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, China.

Background: Data on the correlation between CST4 and colorectal cancer (CRC) metastasis are scarce. The aim of this study was to analyze CST4 expression and investigate its biological roles and related microRNA- (miRNA-) mediated regulation in CRC.

Methods: The expression of CST4 was examined in cancer tissues and their corresponding adjacent normal tissues from 40 gastric adenocarcinoma patients. The expression level of CST4 in specimens (cancer and normal tissues) was assessed through immunohistochemistry and/or quantitative polymerase chain reaction. miRNAs targeting CST4 in CRC were predicted by bioinformatics software. CST4 was knocked down in HCT116 cells and candidate miRNAs were transfected into HCT116 cells, and the effects of CST4 knockdown and miRNA transfection on cell proliferation and invasion were examined using CCK8, cell colony formation, and Transwell migration assays. Luciferase double-reporter assays were performed to verify the relationship between miRNA and CST4.

Results: The expression of CST4 in CRC tissues was significantly higher than that in normal paracancerous tissues, but the results for miRNA-6715-5p were opposite. Regardless of CST4 knockdown or miRNA-6715-5p overexpression, the proliferation and invasion ability of HCT116 cells decreased significantly. Luciferase double-reporter assays showed that the upregulation of miR-6715-5p significantly reduced the luciferase activities of the CST4 3'-UTR plasmid in HCT116 cells.

Conclusion: CST4 may be involved in CRC proliferation and metastasis. miRNA-6715-5p directly targets CST4 and negatively regulates its expression.
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http://dx.doi.org/10.1155/2021/7615712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181091PMC
May 2021

Increasing Fracture Risk Associates With Plasma Circulating MicroRNAs in Aging People's Sarcopenia.

Front Physiol 2021 7;12:678610. Epub 2021 Jun 7.

Department of Cardiology, HwaMei Hospital (Previously Named Ningbo No. 2 Hospital), University of Chinese Academy of Sciences, Ningbo, China.

Aging generally coincides with a gradual decline in mass and strength of muscles and bone mineral density (BMD). Sarcopenia is closely linked to osteoporosis in the elderly, which can lead to abnormal gait, balance disorders, and dysfunctions, as well as increase in the risks of falls, fractures, weakness, and death. MicroRNAs (miRNAs, miRs) are a kind of short and non-coding RNA molecules but can regulate posttranscriptional protein expression. However, we have known little about their participation in age-associated osteoporosis and sarcopenia. The current study aims to confirm those miRNAs as biomarkers for age-related reduction in muscular atrophy associated with human blood fractures. In our study, 10 fracture-risk-related miRNAs (miR-637, miR-148a-3p, miR-125b-5p, miR-124-3p, miR-122-5p, miR-100-5p, miR-93-5p, miR-21-5p, miR-23a-3p, and miR-24-3p) were analyzed. For the initial screening, we determined the abundance of fracture-risk-associated miRNAs by RT-PCR most frequently detected in enrolled 93 elderly with sarcopenia and non-sarcopenia, respectively. Statistically, the relative expression levels of plasma miR-23a-3p, miR-93-5p, and miR-637 in the sarcopenia group were significantly lower than that in the non-sarcopenia group, while the levels of other miRNAs did not change significantly. Moreover, we showed that the levels of ASM/height, handgrip strength, and 4-m velocity in the sarcopenia group were significantly lower than in the non-sarcopenia group. Whereafter, we expanded the sample for further detection and analysis and revealed that the levels of plasma miR-23a-3p, miR-93-5p, and miR-637 in the sarcopenia group were significantly lower than that in the non-sarcopenia group, which is consistent with the initial screening experiment. From our analysis, changes in levels of plasma miR-93-5p and miR-637 were dramatically related to ASM/height. Furthermore, changes in miR-23a and miR-93-5p were significantly affected by ASM/height in female individuals, with no significant correlations between miRNAs changes and these diagnostic indexes in male individuals after adjusting sex. The study showed that plasma miRNAs changed in an aging-related sarcopenia manner and were associated with increased fracture risk. In aging patients, plasma miR-23a-3p, miR-93-5p, and miR-637 have the potential as biomarkers of sarcopenia, which can affect the development of physiological dysfunction and may be also used in the fracture risk assessment of these patients.
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http://dx.doi.org/10.3389/fphys.2021.678610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215392PMC
June 2021

A general strategy for obtaining BiOX nanoplates derived Bi nanosheets as efficient CO reduction catalysts by enhancing CO adsorption and electron transfer.

J Colloid Interface Sci 2021 Nov 4;602:740-747. Epub 2021 Jun 4.

Tianjin Key Laboratory of Advanced Functional Porous Materials, Institute for New Energy Materials and Low-Carbon Technologies, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China. Electronic address:

Electroreduction of carbon dioxide (CO) into formic acid/formate has been considered as one of the most promising strategies for obtaining value-added fuels and chemical productions. Herein, we present a general method for preparing Bi-based electrocatalysts via in situ reduction of bismuth oxyiodide (BiOI) in CO-saturated electrolyte. The precursors of BiOI nanoplates (P-nanoplates) with thickness of 30-40 nm could be easily obtained and provide a concise model to probe the mechanisms of CO reduction to formate. BiOI nanoplates precursors derived Bi nanosheets (P-nanoplates-Bi) exhibited an excellent performance for CO reduction to formate, achieving Faradaic efficiencies (FEs) over 80% in a wide potential window and a maximum FE approaching of 95% with a current density of 13.3 ± 0.6 mA cm at -0.9 V versus reverse hydrogen electrode (υs. RHE). Such P-nanoplates-Bi nanosheets showed a stable electrocatalytic actitivity during 15 h operation in 0.5 M KHCO aqueous solution. The superior performance is mainly attributed to the two-dimensional (2D) Bi nanosheets, which can increase CO adsorption, enlarge active surface area, show better reaction kinetics and provide lower contact resistance with accelerated electron transfer. For comparison, precursors of BiOI plate-like (P-bulk) with doubled thicknesses and ultrathin BiOI with a few nanometers derived Bi catalysts tend to agglomerate and appear as irregular structured Bi nanoparticles during the reaction. Their peak FEs for formate are much lower than those of P-nanoplates derived Bi nanosheets at -0.9 V.
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http://dx.doi.org/10.1016/j.jcis.2021.06.010DOI Listing
November 2021

A study on the morphology of natural microfractures in marine and continental transitional shale based on scanning electron microscopy image.

Micron 2021 09 8;148:103105. Epub 2021 Jun 8.

School of Gemmology and Materials Science, Hebei GEO University, Shijiazhuang, Heibei, 050031, PR China.

The development of natural microfractures not only directly affects exploitation efficiency of a shale gas reservoir, but also determines the quality and production of the shale gas reservoir. The environment, in which the shale forms, is considered to be the fundamental cause of shale pore formation and deformation. However, the traditional method of observing shale samples using field-emission scanning electron microscopy (FE-SEM) can be interfered by a large number of fractures caused by artificial damage on the shale surface during sample preparation, such as mechanical damage during polishing and shrinkage damage of shale mineral particles. To tackle this issue, we summarized the features of natural fractures by comparing fracture morphology of shale before and after artificial damage. In this study, the powder samples which suffered serious structural damage and the block samples with light structural damage were observed by FE-SEM. In addition, we used the pressure switch to cause slight damage to the surface of gold-plated block samples, and the difference between the gold film tearing edge and the mineral tearing edge was used to identify the artificial cracks generated during this process. We found (1) most of the open structural fractures on the shale surface are not natural, but artificially induced during the sample preparation process; (2) most non-structural natural fractures are mainly related to organic matter, clay and calcite; (3) stress and shrinkage are the main causes of natural microfractures; (4) natural microfractures in shale have a clear pressure support structure, which are categorized into self-supporting fractures.
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http://dx.doi.org/10.1016/j.micron.2021.103105DOI Listing
September 2021

Fluoride exposure and children's intelligence: Gene-environment interaction based on SNP-set, gene and pathway analysis, using a case-control design based on a cross-sectional study.

Environ Int 2021 10 4;155:106681. Epub 2021 Jun 4.

Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Background: Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level.

Objectives: Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level.

Methods: A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method.

Results: The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence (P = 0.001) alone and by interaction with water, urinary and hair fluoride (P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men.

Conclusions: Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss.
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http://dx.doi.org/10.1016/j.envint.2021.106681DOI Listing
October 2021

Predicting cancer malignancy and proliferation in glioma patients: intra-subject inter-metabolite correlation analyses using MRI and MRSI contrast scans.

Quant Imaging Med Surg 2021 Jun;11(6):2721-2732

Department of Radiology, the University of Illinois at Chicago, Chicago, Illinois, USA.

Background: The non-invasive characterization of glioma metabolites would greatly assist the management of glioma patients in the clinical setting. This study investigated the applicability of intra-subject inter-metabolite correlation analyses for differentiating glioma malignancy and proliferation.

Methods: A total of 17 negative controls (NCs), 39 low-grade gliomas (LGGs) patients, and 25 high-grade gliomas (HGGs) subjects were included in this retrospective study. Amide proton transfer (APT) and magnetization transfer contrast (MTC) imaging contrasts, as well as total choline/total creatine (tCho/tCr) and total N-acetylaspartate/total creatine (tNAA/tCr) ratios quantified from magnetic resonance spectroscopic imaging (MRSI) were co-registered voxel-wise and used to produce three intra-subject inter-metabolite correlation coefficients (IMCCs), namely, R , R , and R . The correlation between the IMCCs and tumor grade and Ki-67 labeling index (LI) for tumor proliferation were explored. The differences in the IMCCs between the three groups were compared with one-way analysis of variance (ANOVA). Finally, regression analysis was used to build a combined model with multiple IMCCs to improve the diagnostic performance for tumor grades based on receiver operator characteristic curves.

Results: Compared with the NCs, gliomas showed stronger inter-metabolic correlations. R was significantly different among the three groups (NC . LGGs . HGGs: -0.18±0.38 . -0.40±0.34 . -0.70±0.29, P<0.0001). No significant differences were detected in R among the three groups. R and R correlated significantly with tumor grade (R=-0.41, P=0.001 and R=0.448, P<0.001, respectively). However, only R was mildly correlated with Ki-67 (R=-0.33, P=0.02). R and R achieved areas under the curve (AUCs) of 0.754 and 0.71, respectively, for differentiating NCs from gliomas; and 0.77 and 0.78, respectively, for differentiating LGGs from HGGs. The combined multi-IMCCs model improved the correlation with the Ki-67 LI (R=0.46, P=0.0008) and the tumor-grade stratification with AUC increased to 0.85 (sensitivity: 80.0%, specificity: 79.5%).

Conclusions: This study demonstrated that glioma patients showed stronger inter-metabolite correlations than control subjects, and the IMCCs were significantly correlated with glioma grade and proliferation. The multi-IMCCs combined model further improved the performance of clinical diagnosis.
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http://dx.doi.org/10.21037/qims-20-1163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107299PMC
June 2021

Emerging graphitic carbon nitride-based membranes for water purification.

Water Res 2021 Jul 4;200:117207. Epub 2021 May 4.

Center for Water and Ecology, State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China.

Membrane separation is a promising technology that can effectively remove various existing contaminants from water with low energy consumption and small carbon footprint. The critical issue of membrane technology development is to obtain a low-cost, stable, tunable and multifunctional material for membrane fabrication. Graphitic carbon nitride (g-CN) has emerged as a promising membrane material, owing to the unique structure characteristics and outstanding catalytic activity. This review paper outlined the advanced material strategies used to regulate the molecule structure of g-CN for membrane separation. The presentative progresses on the applications of g-CN-based membranes for water purification have been elaborated. Essentially, we highlighted the innovation integration of physical separation, catalysis and energy conversion during water purification, which was of great importance for the sustainability of water treatment techniques. Finally, the continuing challenges of g-CN-based membranes and the possible breakthrough directions in the future research was prospected.
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http://dx.doi.org/10.1016/j.watres.2021.117207DOI Listing
July 2021

Correlation of prostatic morphological parameters and clinical progression in aging Chinese men with benign prostatic hyperplasia: Results from a cross-sectional study.

Prostate 2021 Jun 16;81(8):478-486. Epub 2021 Apr 16.

Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Our study aimed to investigate the correlation of prostatic morphological parameters and benign prostatic hyperplasia (BPH) clinical progression in aging Chinese men.

Methods: In this retrospective study, a total of 1038 patients were reviewed. Prostatic morphology was measured by transrectal ultrasound (TRUS). Detailed medical history of all candidates was recorded and analyzed after being classified by specific prostatic measurements. Univariate and multivariate logistic regression analyses were used to estimate the correlation between variables.

Results: The cumulative incidence of BPH clinical progression was 63.68% (661/1038) in the study population. Prostate volume (PV), transitional zone volume (TZV), transitional zone index (TZI), and intravesical prostatic protrusion (IPP) were all positively associated with BPH progression (all p < .001). Patients with a PV > 60 ml, TZV > 15 ml, TZI > 0.5, or IPP > 5 mm had a significantly higher possibility of overall BPH clinical progression (adjusted odds ratio (OR): 2.485, 1.678, 1.886, and 1.924, respectively; 95% confidence interval (CI): 1.559-3.960, 1.131-2.489, 1.379-2.579, and 1.357-2.728, correspondingly).

Conclusion: Prostatic morphological parameters are significantly associated with BPH clinical progression. Patients with larger prostatic morphological parameters are more easily prone to clinical progress. As a result, reasonable managements should be timely considered for those patients before clinical progression occurs.
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http://dx.doi.org/10.1002/pros.24128DOI Listing
June 2021

Role of hsa‑miR‑105 during the pathogenesis of paclitaxel resistance and its clinical implication in ovarian cancer.

Oncol Rep 2021 05 13;45(5). Epub 2021 Apr 13.

Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

More than 70% of patients with epithelial ovarian cancer (EOC), one of the leading cause of gynecological cancer‑related deaths worldwide, are diagnosed at an advanced stage of the disease. Currently, the mainstay for treatment of advanced EOC is tumor debulking surgery followed by combined platinum‑ and paclitaxel (PTX)‑based chemotherapy. However, most patients eventually develop chemoresistance, which remains a major obstacle to successful treatment. Herein, by using clinical specimens and experimentally induced cell models, we found that the expression levels of hsa‑miR‑105 were significantly decreased in PTX‑resistant EOC tissues and cell lines. Follow‑up functional experiments demonstrated that repression of hsa‑miR‑105 conferred resistance to paclitaxel in EOC cells, whereas restoration of hsa‑miR‑105 expression via intratumoral injection of hsa‑miR‑105 micrON™ agomir potentiated sensitivity to PTX and thereafter significantly inhibited tumor growth in a PTX‑challenged xenograft model. Mechanistically, hsa‑miR‑105 exerted its tumor suppressor function by directly inhibiting the zinc and ring finger 2 (ZNRF2) signaling pathway. Importantly, aberrant expression of hsa‑miR‑105 in both tumor and circulating samples predicted a poor post‑chemotherapy prognosis in EOC patients. These findings collectively suggest that hsa‑miR‑105 may act as a potent tumor suppressor miRNA during the progression of EOC, likely affecting cell proliferation, invasiveness and chemosensitivity to PTX, and functioning at least in part via inhibition of ZNRF2 signaling. The stability and availability and ease in measurement of circulating hsa‑miR‑105 make it a valuable diagnostic/prognostic biomarker candidate for chemotherapy of EOC.
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http://dx.doi.org/10.3892/or.2021.8035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025119PMC
May 2021

PPARγ induces the paroxysm of endometriosis by regulating the transcription of MAT2A gene.

Am J Transl Res 2021 15;13(3):1377-1388. Epub 2021 Mar 15.

The First Affiliated Hospital of Nanchang University No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, People's Republic of China.

Objective: To investigate the molecular mechanism of PPARγ impacting the paroxysm of endometriosis.

Methods: Immunohistochemistry, qRT-PCR and Western Blot were used to determine the expression level of PPARγ and MAT2A in Eu, Ec and normal endometrial tissue (control). ESC and NSC were separately isolated. PPARγ was silenced in NSC and was up-regulated in ESC. Rosiglitazone (RSG) were used to incubate with ESC. Proliferation, apoptosis, invasion, and ultrastructure of cells were evaluated in vitro. The combination between PPARγ and the promoters of MAT2A was detected by dual-luciferase reporter assay.

Results: MAT2A was up-regulated and PPARγ was down-regulated in Eu and Ec. The cell viability and the ability of migration and invasion declined greatly after up-regulating the expression of PPARγ or treating with RSG in ESC. Meanwhile, the expression level of MAT2A was significantly inhibited. Plenty of vacuoles and classical morphological changes of apoptotic cells were observed in the ESC with PPARγ over-expressed. The cell viability and the ability of migration and invasion of NSC with PPARγ silenced were promoted greatly. Meanwhile, the expression level of MAT2A was significantly up-regulated.

Conclusion: The paroxysm and development of endometriosis were impacted by over-expressing PPARγ or introducing of RSG by inhibiting the transcription of MAT2A.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014359PMC
March 2021
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