Publications by authors named "Liming Wang"

711 Publications

Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China: A case-control study.

Synth Syst Biotechnol 2021 Jun 21;6(2):120-126. Epub 2021 May 21.

Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China.

Background: Autism spectrum disorders (ASDs) are a set of complex neurobiological disorders. Growing evidence has shown that the microbiota that resides in the gut can modulate brain development via the gut-brain axis. However, direct clinical evidence of the role of the microbiota-gut-brain axis in ASD is relatively limited.

Methods: A case-control study of 71 boys with ASD and 18 neurotypical controls was conducted at China-Japan Friendship Hospital. Demographic information and fecal samples were collected, and the gut microbiome was evaluated and compared by 16S ribosomal RNA gene sequencing and metagenomic sequencing.

Results: A higher abundance of operational taxonomic units (OTUs) based on fecal bacterial profiling was observed in the ASD group. Significantly different microbiome profiles were observed between the two groups. At the genus level, we observed a decrease in the relative abundance of in the ASD cohort, while and were significantly increased. Ten bacterial strains were selected for clinical discrimination between those with ASD and the neurotypical controls. The highest AUC value of the model was 0.947.

Conclusion: Significant differences were observed in the composition of the gut microbiome between boys with ASD and neurotypical controls. These findings contribute to the knowledge of the alteration of the gut microbiome in ASD patients, which opens the possibility for early identification of this disease.
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http://dx.doi.org/10.1016/j.synbio.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163862PMC
June 2021

Circular RNA circLMF1 regulates PDGF-BB-induced proliferation and migration of human aortic smooth muscle cells by regulating the miR-125a-3p/VEGFA or FGF1 axis.

Clin Hemorheol Microcirc 2021 Jun 1. Epub 2021 Jun 1.

Department of Cardiac Surgery, The Cardio-Cerebro Vascular Disease Specialist Hospital of Qinghai Province, Xining City, China.

Atherosclerosis is a major cause of cardiovascular disease, in which vascular smooth muscle cells (VSMCs) proliferation and migration play a vital role. Circular RNAs (circRNAs) have been reported to be correlated with the VSMCs function. Therefore, this study is designed to explore the role and mechanism of circRNA lipase maturation factor 1 (circLMF1) in Human aortic VSMCs (HASMCs). The microarray was used for detecting the expression of circLMF1 in proliferative and quiescent HASMCs. Levels of circLMF1, microRNA-125a-3p (miR-125a-3p), vascular endothelial growth factor A (VEGFA), and fibroblast growth factor 1 (FGF1) were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, cell cycle progression, and migration were assessed by Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and transwell assays, respectively. Western blot assay determined proliferating cell nuclear antigen (PCNA), Cyclin D1, matrix metalloproteinase (MMP2), osteopontin (OPN), VEGFA, and FGF1 protein levels. The possible interactions between miR-125a-3p and circLMF1, and miR-125a-3p and VEGFA or FGF1 were predicted by circbank or targetscan, and then verified by a dual-luciferase reporter, RNA Immunoprecipitation (RIP), RNA pull-down assays. CircLMF1, VEGFA, and FGF1 were increased, and miR-125a-3p was decreased in platelet-derived growth factor-BB (PDGF-BB)-inducted HASMCs. Functionally, circLMF1 knockdown hindered cell viability, cell cycle progression, and migration in PDGF-BB-treated HASMCs. Mechanically, circLMF1 could regulate VEGFA or FGF1 expression through sponging miR-125a-3p. Our findings revealed that circLMF1 deficiency could inhibit cell viability, cell cycle progression, and migration of PDGF-BB stimulated atherosclerosis model partly through the miR-125a-3p/VEGFA or FGF1 axis, suggesting that targeting circLMF1 can be a feasible therapeutic strategy for atherosclerosis.
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http://dx.doi.org/10.3233/CH-211166DOI Listing
June 2021

Prognostic and predictive significance of the tumor microenvironment in hepatocellular carcinoma.

Cancer Biomark 2021 May 28. Epub 2021 May 28.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Identification of molecular markers that reflect the characteristics of the tumor microenvironment (TME) may be beneficial to predict the prognosis of post-operative hepatocellular carcinoma (HCC) patients.

Objective And Methods: A total of 100 tissue samples from HCC patients were separately stained by immunohistochemistry to examine the expression levels of CD56, CD8α, CD68, FoxP3, CD31 and pan-Keratin. The prognostic values were analyzed by Cox regression and the Kaplan-Meier method.

Results: Univariate and multivariate logistic analysis showed that FoxP3 was the independent factor associated with microvascular invasion (MVI), tumor size and envelop invasion; CD68 was associated with envelope invasion and AFP. Kaplan-Meier survival curves revealed that CD68 and FoxP3 expression were significantly associated with relapse free survival (RFS) of HCC patients (P< 0.05). The ROC curve indicated that the combination of tumor number, MVI present and CD68 expression yielded a ROC curve area of 82.3% (86.36% specificity, 68.75% sensitivity) to evaluate the prognosis of HCC patients, which was higher than the classifier established by the combination of tumor number and MVI (78.8% probability, 63.64% specificity and 85.42% sensitivity).

Conclusions: Our study indicated that CD68 and FoxP3 are associated with prognosis of HCC patients, and CD68 can be considered as a potential prognostic and predictive biomarker.
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http://dx.doi.org/10.3233/CBM-203003DOI Listing
May 2021

Heterologous expression of ZmGS5 enhances organ size and seed weight by regulating cell expansion in Arabidopsis thaliana.

Gene 2021 May 30;793:145749. Epub 2021 May 30.

Maize Research Institute, Shandong Academy of Agricultural Sciences/National Engineering Laboratory of Wheat and Maize/Key Laboratory of Biology and Genetic Improvement of Maize in Northern Yellow-huai River Plain, Ministry of Agriculture, Jinan 250100, China. Electronic address:

Maize ZmGS5 was reported to be positively associated with kernel-related traits, however, its regulatory mechanism on plant development and seed size remains unknown. In this study, ZmGS5 was demonstrated to be widely expressed in various maize tissues with the highest expression level in developing embryos, indicating its critical roles in early kernel development process. The ZmGS5 protein was subcellularly localized to both the nucleus and cytoplasm. Transgenic Arabidopsis plants overexpressing ZmGS5 under the control of either the constitutive maize Ubiquitin1 promotor or native ZmGS5 promoter resulted in increased plant size, biomass, seed size and weight, although no significant difference was observed between transgenic lines harboring the two constructs. In contrast, the antisense-ZmGS5 transgene resulted in opposite phenotypes. Our cytological data suggested that ZmGS5 enlarged petal size through enhancing cell expansion. Quantitative RT-PCR analysis indicated that ZmGS5 might enhance cell expansion and grain filling by upregulating expression levels of particular EXPA or SWEET genes. Collectively, these findings help us further understand the biological function and regulatory mechanism of ZmGS5 in improving organ size and seed weight, which imply its great potential for high-yield breeding in the future.
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http://dx.doi.org/10.1016/j.gene.2021.145749DOI Listing
May 2021

High-resolution genome-wide association study and genomic prediction for disease resistance and cold tolerance in wheat.

Theor Appl Genet 2021 Jun 1. Epub 2021 Jun 1.

State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an 271018, China.

Key Message: High-resolution genome-wide association study (GWAS) facilitated QTL fine mapping and candidate gene identification, and the GWAS based genomic prediction models were highly predictive and valuable in wheat genomic breeding. Wheat is a major staple food crop and provides more than one-fifth of the daily calories and dietary proteins for humans. Genome-wide association study (GWAS) and genomic selection (GS) for wheat stress resistance and tolerance related traits are critical to understanding their genetic architecture for improvement of breeding selection efficiency. However, the insufficient marker density in previous studies limited the utility of GWAS and GS in wheat genomic breeding. Here, we conducted a high-resolution GWAS for wheat leaf rust (LR), yellow rust (YR), powdery mildew (PM), and cold tolerance (CT) by genotyping a panel of 768 wheat cultivars using genotyping-by-sequencing. Among 153 quantitative trait loci (QTLs) identified, 81 QTLs were delimited to ≤ 1.0 Mb intervals with three validated using bi-parental populations. Furthermore, 837 stress resistance-related genes were identified in the QTL regions with 12 showing induced expression by YR and PM pathogens. Genomic prediction using 2608, 4064, 3907, and 2136 pre-selected SNPs based on GWAS and genotypic correlations between the SNPs showed high prediction accuracies of 0.76, 0.73, and 0.78 for resistance to LR, YR, and PM, respectively, and 0.83 for resistance to cold damage. Our study laid a solid foundation for large-scale QTL fine mapping, candidate gene validation and GS in wheat.
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http://dx.doi.org/10.1007/s00122-021-03863-6DOI Listing
June 2021

Biotransformation of soluble-insoluble lanthanum species and its induced NLRP3 inflammasome activation and chronic fibrosis.

Environ Pollut 2021 May 22;284:117438. Epub 2021 May 22.

Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, Jilin, China; University of Science and Technology of China, Hefei, PR China. Electronic address:

Soluble lanthanum (La)(Ⅲ) species that have been extensively used as fertilizers in agriculture can potentially get into the human body through foods and environment. Most soluble La(Ⅲ) species can rapidly transform into insoluble La(Ⅲ) species under physiological conditions, however, their potential biological behavior and chronic toxicity are rarely investigated. In the present study, insoluble La(Ⅲ) species formed under physiological condition were identified as nanoscale or microscale particles, and their major components were found to experience biotransformation process upon contact with cells. Insoluble La(Ⅲ) species could adhere to extracellular membrane or be internalized into cells, capable of activating a nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. The underlying mechanism could be ascribed to K efflux and lysosomal rupture because these insoluble La(Ⅲ) species locating at extracellular membrane could reduce the unsaturated fatty acids of cell membrane, leading to potassium (K) efflux, and those internalized into cells could consume the phospholipids of lysosomal membrane, leading to lysosomal rupture. Mice daily drinking soluble La(Ⅲ) species to mimic drinking tea process for 90 days were found to present NLRP3 inflammasome activation in liver and kidney, as a result of chronic fibrosis, which is potentially correlated to insoluble La(Ⅲ) species formation.
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http://dx.doi.org/10.1016/j.envpol.2021.117438DOI Listing
May 2021

33-kDa ANXA3 isoform contributes to hepatocarcinogenesis modulating ERK, PI3K/Akt-HIF and intrinsic apoptosis pathways.

J Adv Res 2021 May 8;30:85-102. Epub 2020 Nov 8.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Introduction: As a member of annexin family proteins, annexin A3 (ANXA3) has 36-kDa and 33-kDa isoforms. ANXA3 plays crucial roles in the tumorigenesis, aggressiveness and drug-resistance of cancers. However, previous studies mainly focused on the role of total ANXA3 in cancers without distinguishing the distinction between the two isoforms, the role of 33-kDa ANXA3 in cancer remains unclear.

Objectives: Current work aimed to investigate the function and regulation mechanism of 33-kDa ANXA3 in hepatocarcinoma.

Methods: The expressions of ANXA3, CRKL, Rac1, c-Myc and pAkt were analyzed in hepatocarcinoma specimens by Western blotting. The biological function of 33-kDa ANXA3 in the growth, metastasis, apoptosis, angiogenesis, chemoresistance of hepatocarcinoma cells with the underlying molecular mechanism were investigated using gain-of-function strategy or .

Results: 33-kDa ANXA3 was remarkably upregulated in tumor tissues compared with corresponding normal liver tissues of hepatocarcinoma patients. Its stable knockdown decreased the tumor growing velocity and malignancy of hepatocarcinoma HepG2 cells transplanted in nude mice. The experimental results indicated 33-kDa ANXA3 knockdown suppressed the proliferation, colony forming, migration and invasion abilities of HepG2 cells through downregulating CRKL, Rap1b, Rac1, pMEK, pERK2 and c-Myc in ERK pathway; inhibited angiogenesisability of HepG2 cells through inactivating PI3K/Akt-HIF pathway; induced apoptosis and enhanced chemoresistance of HepG2 cells through increasing Bax/decreasing Bcl-2 expressions and inactivating caspase 9/caspase 3 in intrinsic apoptosis pathway. Accordingly, CRKL, Rac1, c-Myc and pAkt were also upregulated in hepatocarcinoma patients ' tumor tissues compared with corresponding normal liver tissues.

Conclusions: The overexpression of 33-kDa ANXA3 is involved in the clinical progression of hepatocarcinoma and in the malignancy, angiogenesis and apoptosis of hepatocarcinoma cells. It is of potential use in hepatocarcinoma diagnosis and treatment.
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http://dx.doi.org/10.1016/j.jare.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132212PMC
May 2021

Serum microRNAs predict response of patients with chronic hepatitis B to antiviral therapy.

Int J Infect Dis 2021 May 14;108:37-44. Epub 2021 May 14.

Hepatology and Cancer Biotherapy Ward/Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address:

Objectives: To investigate the feasibility of using serum microRNAs to predict the response of chronic hepatitis B (CHB) patients to antiviral therapy over 48 weeks.

Methods: Sixty-five CHB patients were divided into responder and non-responder groups according to whether hepatitis B e antigen seroconversion occurred at week 48. Serum microRNAs were dynamically detected.

Results: At baseline, the responder group had lower miR-122-5p (P = 0.006) and higher miR-1307-3p (P = 0.018) than the non-responder group. After therapy, miR-320a-3p and miR-320c were higher in the responder group than the non-responder group (P = 0.043 and 0.031, respectively). In the responder group, 9 microRNAs-let-7d-5p, let-7f-5p, let-7i-5p, miR-126-3p, miR-1307-3p, miR-181a-5p, miR-21-5p, miR-425-5p and miR-652-3p-were significantly lower at week 48 than at baseline (P < 0.05); however, miR-320a-3p was significantly elevated after therapy (P < 0.001). In the non-responder group, miR-122-5p significantly decreased after therapy compared with baseline (P = 0.005). Finally, miR-122-5p was positively correlated with titer of hepatitis B virus DNA (r = 0.438, P = 0.008) and hepatitis B e antigen (r = 0.610, P < 0.001), and miR-320a-3p was negatively correlated with hepatitis B virus DNA titer (r = -0.366, P = 0.028) at baseline.

Conclusions: The dynamic fluctuations of serum microRNAs might predict the efficacy of antiviral therapy for CHB.
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http://dx.doi.org/10.1016/j.ijid.2021.05.015DOI Listing
May 2021

Automatic classification of heterogeneous slit-illumination images using an ensemble of cost-sensitive convolutional neural networks.

Ann Transl Med 2021 Apr;9(7):550

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Lens opacity seriously affects the visual development of infants. Slit-illumination images play an irreplaceable role in lens opacity detection; however, these images exhibited varied phenotypes with severe heterogeneity and complexity, particularly among pediatric cataracts. Therefore, it is urgently needed to explore an effective computer-aided method to automatically diagnose heterogeneous lens opacity and to provide appropriate treatment recommendations in a timely manner.

Methods: We integrated three different deep learning networks and a cost-sensitive method into an ensemble learning architecture, and then proposed an effective model called CCNN-Ensemble [ensemble of cost-sensitive convolutional neural networks (CNNs)] for automatic lens opacity detection. A total of 470 slit-illumination images of pediatric cataracts were used for training and comparison between the CCNN-Ensemble model and conventional methods. Finally, we used two external datasets (132 independent test images and 79 Internet-based images) to further evaluate the model's generalizability and effectiveness.

Results: Experimental results and comparative analyses demonstrated that the proposed method was superior to conventional approaches and provided clinically meaningful performance in terms of three grading indices of lens opacity: area (specificity and sensitivity; 92.00% and 92.31%), density (93.85% and 91.43%) and opacity location (95.25% and 89.29%). Furthermore, the comparable performance on the independent testing dataset and the internet-based images verified the effectiveness and generalizability of the model. Finally, we developed and implemented a website-based automatic diagnosis software for pediatric cataract grading diagnosis in ophthalmology clinics.

Conclusions: The CCNN-Ensemble method demonstrates higher specificity and sensitivity than conventional methods on multi-source datasets. This study provides a practical strategy for heterogeneous lens opacity diagnosis and has the potential to be applied to the analysis of other medical images.
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http://dx.doi.org/10.21037/atm-20-6635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105862PMC
April 2021

Infrared broadband enhancement of responsivity in Ge photodetectors decorated with Au nanoparticles.

Opt Express 2021 Apr;29(9):12941-12949

A broadband, high-performance infrared Ge photodetector decorated with Au nanoparticles (NPs) is proposed. Photoelectronic characterization demonstrated that the responsivity of devices decorated with Au NPs is as high as 3.95 A/W at a wavelength of 1550 nm. Compared with a Ge photodetector without Au NPs, the responsivity of a device decorated with Au NPs is significantly increased, i.e., by more than 10 times in the entire range of infrared communication wavelengths, including the O, E, S, C, L, and U bands. The increase is ascribed to type-II energy-band alignment between Ge covered with Au NPs and bare Ge, instead of the localized surface-plasmon-resonance effect. The type-II energy-band alignment enhances the spatial electron-hole separation and restrains the electron-hole recombination, thus a larger photocurrent is observed. These results reflect the potential of this approach for achieving broadband, high-performance Ge photodetectors operating in the near-infrared communication band.
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http://dx.doi.org/10.1364/OE.423899DOI Listing
April 2021

Laparoscopic surgical treatment for hydrocele of canal of Nuck: A case report and literature review.

Surg Case Rep 2021 May 13;7(1):121. Epub 2021 May 13.

Department of Surgery, Sapporo Higashi Tokushukai Hospital, 3-1, N-33, E-14, Higahi-ku, Sapporo, Hokkaido, 0650033, Japan.

Background: Hydrocele of canal of Nuck (HCN) is a rare disease in adult female. The diagnosis and treatment of HCN is still a challenge for surgeons.

Case Presentation: A 56-year-old female presented with recent onset of occasional pain during exercise and an asymptomatic left groin swelling. Ultrasonography results were suspicious for left inguinal hernia incarceration and computed tomography (CT) scan showed no intestinal obstruction, which was considered as HCN. Laparoscopic hydrocelectomy of the HCN and a routine laparoscopic hernia repair via the transabdominal preperitoneal (TAPP) approach were performed. Postoperative pathology showed no malignant lesions or endometriosis.

Conclusions: The preoperative diagnosis of HCN is extremely important. Surgeons should choose appropriate surgical methods for different anatomical HCNs based on the preoperative diagnosis.
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http://dx.doi.org/10.1186/s40792-021-01205-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119562PMC
May 2021

Induced Autophagy of Macrophages and the Regulation of Inflammatory Effects by Perovskite Nanomaterial LaNiO.

Front Immunol 2021 22;12:676773. Epub 2021 Apr 22.

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety & CAS-HKU Joint Laboratory of Metallomics on Health and Environment, and Beijing Metallomics Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.

Perovskite nanomaterials (NMs) possess excellent physicochemical properties and have promising applications in light-emitting diodes (LEDs), lasers, photodetectors, and artificial synapse electronics. Potential exposure to these NMs happens in the manufacture and application of the perovskite-based products, however, the biological safety of these NMs is still unknown. Here, we used the LaNiO NM (LNO), a typical kind of perovskite nanostructures to study the interaction with macrophages (J774A.1) and to explore its biological effects at the cellular level. Firstly, we characterized the properties of LNO including the size, shape, and crystal structure using Transmission electronic microscope (TEM), Dynamic lighting scattering (DLS), and X-ray diffraction (XRD). Secondly, to gain a better understanding of the biological effect, we evaluated the effect of LNO on cell viability and found that LNO induced cell autophagy at a concentration of 5 μg/ml and influenced the inflammatory response based on RT-PCR result. Finally, we demonstrated the mechanism that LNO causes cell autophagy and immune response is probably due to the metal ions released from LNO in acidic lysosomes, which triggered ROS and increased lysosomal membrane permeation. This study indicates the safety aspect of perovskite NMs and may guide the rational design of perovskite NMs with more biocompatibility during their manufacture and application.
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http://dx.doi.org/10.3389/fimmu.2021.676773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100511PMC
April 2021

COVID-19, Diabetes, and Associated Health Outcomes in China: Results from a Nationwide Survey of 10 545 Adults.

Horm Metab Res 2021 May 7;53(5):301-310. Epub 2021 May 7.

Global Health Institute, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.

This study examined the associations between diabetes and self-reported/familial COVID-19 infection and investigated health-related outcomes among those with diabetes during China's nationwide quarantine. The 2020 China COVID-19 Survey was administered anonymously via social media (WeChat). It was completed by 10 545 adults in all of mainland China's 31 provinces. The survey consisted of 74 items covering sociodemographic characteristics, preventive measures for COVID-19, lifestyle behaviors, and health-related outcomes during the period of quarantine. Regression models examined associations among study variables. Diabetes was associated with a six-fold increased risk of reporting COVID-19 infection among respondents or their family members. Among people with diabetes, individuals who rarely wore masks had double the risk of suspected COVID-19 infection compared with those who always wore masks, with an inverse J-shaped relationship between face mask wearing and suspected COVID-19 infection. People with diabetes tended to have both poor knowledge of COVID-19 and poor compliance with preventive measures, despite perceiving a high risk of personal infection (40.0% among respondents reporting diabetes and 8.0% without diabetes). Only 54-55% of these respondents claimed to consistently practice preventive measures, including wearing face masks. Almost 60% of those with diabetes experienced food or medication shortages during the quarantine period, which was much higher than those without diabetes. Importantly, respondents who experienced medication shortages reported a 63% higher COVID-19 infection rate. Diabetes was associated with an increased risk of self-reported personal and family member COVID-19 infection, which is mitigated by consistent use of face masks.
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http://dx.doi.org/10.1055/a-1468-4535DOI Listing
May 2021

Aluminum-Based Surface Polymerization on Carbon Dots with Aggregation-Enhanced Luminescence.

J Phys Chem Lett 2021 May 7;12(19):4530-4536. Epub 2021 May 7.

Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Avenida da Universidade Taipa 999078, Macau, SAR P. R. China.

Aggregation-induced luminescence quenching of carbon nanodots (CDs) is the main obstacle for their applications in solid-state light emitting devices. Herein, we developed a one-step synthesis of solid-state emissive CDs with surface aluminum-based polymerization by adding AlCl in citric acid and urea via a microwave-heating dehydration process. Due to the strong coordination ability of Al ions with N and O atoms, considerable steric hindrance of Al-based cross-linked polymerization was introduced on the surface of the CDs, which not only avoided aggregation of the green emissive carbon cores but also facilitated efficient energy transfer from the blue emissive polymerized surface to the green emissive carbon cores in aggregates, leading to enhanced green emissions with a photoluminescence quantum yield (PLQY) of 72.7% in the solid state.
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http://dx.doi.org/10.1021/acs.jpclett.1c01240DOI Listing
May 2021

Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy.

Clin Kidney J 2021 May 27;14(5):1458-1468. Epub 2021 Jan 27.

Department of Nephrology, Daping Hospital, Army Medical University, Chongqing, China.

Background: Accelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN.

Methods: We included a retrospective cohort of 105 patients with biopsy-proven IgAN. Tubular DcR2 expression was assessed at renal biopsy and the Oxford histological MEST-C score [mesangial hypercellularity (M), endocapillary proliferation (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C)] defined disease severity. IgAN progression was defined as a composite of end-stage renal disease or a 30% decline in the estimated glomerular filtration rate (eGFR), analyzed using Kaplan-Meier and Cox regression analyses.

Results: Tubular DcR2 was overexpressed in IgAN. Numbers of DcR2 and p16 double-positive RTECs increased with increasing severity of tubular atrophy/interstitial fibrosis (T lesion). Patients with ≥25% tubular DcR2 expression experienced worse proteinuria, T lesions and a lower eGFR. Cumulative renal survival was significantly lower in patients with ≥25% DcR2 positivity. Multivariate regression analyses showed that ≥25% tubular DcR2 expression was significantly associated with worse eGFR slopes (the rate of renal function decline; P = 0.003) and the incidence of the composite outcome (P = 0.001) in IgAN. The addition of tubular DcR2 to a model with clinical data at biopsy (mean arterial pressure, proteinuria and eGFR) or MEST-C score significantly improved the 5-year risk prediction of IgAN progression, as confirmed by receiver operating characteristic curve analyses.

Conclusions: Tubular DcR2 expression detected at biopsy was a strong independent predictor for IgAN progression and might have prognostic value in addition to established risk markers.
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http://dx.doi.org/10.1093/ckj/sfaa257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087134PMC
May 2021

The oxidation mechanism of gas-phase ozonolysis of limonene in the atmosphere.

Phys Chem Chem Phys 2021 Apr;23(15):9294-9303

School of Chemistry & Chemical Engineering, South China University of Technology, 381 Wushan Rd., Guangzhou, 510640, China. and Guangdong Provincial Key Laboratory of Atmospheric Environment and Pollution Control, South China University of Technology, Guangzhou 510006, China.

Limonene with endo- and exo-double bonds is a significant monoterpene in the atmosphere and has high reactivity towards O3. We investigated the atmospheric oxidation mechanism of limonene ozonolysis using a high level quantum chemistry calculation coupled with RRKM-ME kinetic simulation. The additions of O3 can take place at both the endo- and exo-double bonds with a branching ratio of 0.87 : 0.13, forming four major highly energized CIs* (named Syn-2a*, Syn-2b*, Anti-2b* and Anti-2c*) with the relative higher fractions of 0.21 : 0.35 : 0.27 : 0.11. A yield of 4% for Limona-ketone was obtained as well. For the unimolecular isomerization pathways of limonene + O3 → POZs → CIs* → SOZ, VHP, or dioxirane, five, one, or none of the internal rotations are treated as hindered internal rotors for CIs*. We obtained percentages of 0.59 : 0.18 : 0.14 in total for separate isomerization routes in the formation of VHPs, dioxirane and SOZs from CIs* using the fourth-order Runge-Kutta method. Additionally, a yield of ∼5% was acquired for stabilized CIs compiling the fractions of different addition routes. About ∼10% of stabilized Anti-2b would isomerize to VHP and 90% would isomerize to SOZs. Isomerization to VHPs dominates the fate of stabilized Syn-2a, Syn-2b and Anti-2c. The overall yield of OH radicals was 0.61. Our study suggested a yield of 0.17 for stabilized SOZs and 0.18 for dioxirane, although both their fates are ambiguous.
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http://dx.doi.org/10.1039/d0cp05803cDOI Listing
April 2021

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 () Gene Confers Enhanced Calcineurin Activity and May Cause FSGS.

J Am Soc Nephrol 2021 Apr 16. Epub 2021 Apr 16.

Division of Nephrology, Department of Pediatrics, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina

Background: Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified.

Methods: Whole-genome sequencing was performed on 320 individuals from 201 families with familial and sporadic NS/FSGS with no pathogenic mutations in any known NS/FSGS genes.

Results: Two variants in the gene encoding regulator of calcineurin type 1 () segregate with disease in two families with autosomal dominant FSGS/SRNS. , loss of reduced human podocyte viability due to increased calcineurin activity. Cells expressing mutant displayed increased calcineurin activity and NFAT activation that resulted in increased susceptibility to apoptosis compared with wild-type . Treatment with GSK-3 inhibitors ameliorated this elevated calcineurin activity, suggesting the mutation alters the balance of RCAN1 regulation by GSK-3, resulting in dysregulated calcineurin activity and apoptosis.

Conclusions: These data suggest mutations in can cause autosomal dominant FSGS. Despite the widespread use of calcineurin inhibitors in the treatment of NS, genetic mutations in a direct regulator of calcineurin have not been implicated in the etiology of NS/FSGS before this report. The findings highlight the therapeutic potential of targeting RCAN1 regulatory molecules, such as GSK-3, in the treatment of FSGS.
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http://dx.doi.org/10.1681/ASN.2020081234DOI Listing
April 2021

Ubiquitin-specific protease 22 ameliorates chronic alcohol-associated liver disease by regulating BRD4.

Pharmacol Res 2021 Jun 4;168:105594. Epub 2021 Apr 4.

Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian 116000, China. Electronic address:

Alcohol-associated liver disease (ALD) is a liver system disease caused by alcohol abuse, and it involves complex processes ranging from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. Steatosis and inflammation are the main phenomena involved in ALD. Ubiquitin-specific protease 22 (USP22) plays an important role in liver steatosis; however, its functional contribution to ALD remains unclear. USP22-silenced mice were fed a Lieber-DeCarli liquid diet. AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4. Here, we report that hepatic USP22 expression was dramatically upregulated in mice with ALD. Inflammation and steatosis were significantly ameliorated following USP22 silencing in vivo, as indicated by decreased IL-6 and IL-1β levels. We further showed that the overexpression of USP22 increased inflammation, while knocking down BRD4 suppressed the inflammatory response in AML-12 cells. Notably, USP22 functioned as a BRD4 deubiquitinase to facilitate BRD4 inflammatory functions. More importantly, the expression levels of USP22 and BRD4 in patients with ALD were significantly increased. In conclusion, USP22 acts a key pathogenic factor in ALD by deubiquitinating BRD4, which facilitates the inflammatory response and aggravates ALD.
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http://dx.doi.org/10.1016/j.phrs.2021.105594DOI Listing
June 2021

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open-label phase II study (ALTER-0802 study).

Hepatol Int 2021 Apr 7. Epub 2021 Apr 7.

Department of Medical Imaging, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.

Purpose: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.

Methods: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12 mg/day, Day1-14, 3 weeks per cycle). The primary endpoint was 12-week progression-free survival (PFS) rate. Relationship between the series plasma cytokine level and the efficacy of anlotinib was analyzed.

Results: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% [95% confidence interval (CI); 59.8%-91.5%] and median time to progression (TTP) was 5.9 months (95% CI 4.8-6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI 48.7%-86.6%) and 4.6 months (95% CI 2.7-10.0), respectively. The median TTP on patients with a baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significantly longer in both cohorts. The most common grade 3-5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%).

Conclusion: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for the efficacy of anlotinib.
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http://dx.doi.org/10.1007/s12072-021-10171-0DOI Listing
April 2021

Metaplastic breast carcinoma: a retrospective study of 26 cases.

Int J Clin Exp Pathol 2021 1;14(3):355-362. Epub 2021 Mar 1.

Department of Pathology, The First Affiliated Hospital of Bengbu Medical College Bengbu, Anhui Province, China.

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994148PMC
March 2021

Comparative nanometallomics as a new tool for nanosafety evaluation.

Metallomics 2021 04;13(4)

University of Chinese Academy of Sciences, Beijing 100049, China.

Nanosafety evaluation is paramount since it is necessary not only for human health protection and environmental integrity but also as a cornerstone for industrial and regulatory bodies. The current nanometallomics did not cover non-metallic nanomaterials, which is an important part of nanomaterials. In this critical review, the concept of nanometallomics was expanded to incorporate all nanomaterials. The impacts on metal(loid) and metallo-biomolecular homeostasis by nanomaterials will be focused upon in nanometallomics study. Besides, the impacts on elemental and biomolecular homeostasis by metallo-nanomaterials are also considered as the research subjects of nanometallomics. Based on the new concept of nanometallomics, comparative nanometallomics was proposed as a new tool for nanosafety evaluation, which is high throughput and will be precise considering the nature of machine learning techniques. The perspectives of nanometallomics like metallo-wide association study and non-target nanometallomics were put forward.
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http://dx.doi.org/10.1093/mtomcs/mfab013DOI Listing
April 2021

Silencing of CREB Inhibits HDAC2/TLR4/NF-κB Cascade to Relieve Severe Acute Pancreatitis-Induced Myocardial Injury.

Inflammation 2021 Mar 16. Epub 2021 Mar 16.

Department of Emergency, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xincheng District, 710004, Xi'an, Shaanxi Province, People's Republic of China.

The purpose of the present study is to investigate the role of CREB in cardiomyocytes proliferation in regulation of HDAC2-dependent TLR4/NF-κB pathway in severe acute pancreatitis (SAP)-induced myocardial injury. The SAP rat model was developed by injecting sodium touracholate into SD rats and then infected with lentivirus vectors expressing sh-CREB in the presence/absence of LPS. The pathological alterations of rat pancreatic and cardiac tissues were observed by HE staining. TUNEL assay was used to study apoptosis of cardiomyocytes. Next, the loss- and gain-function assay was conducted in LPS-induced myocardial injury cardiomyocytes to define the roles of CREB, HDAC2, and TLR4 in cardiomyocyte proliferation, apoptosis, inflammation, and myocardial injury in vitro. ChIP assay was used to study the enrichment of CREB bound to HDAC2 promoter. RT-qPCR and Western blot analysis were used to detect the expressions of related mRNA and proteins in the NF-κB pathway, respectively. CREB was found to be overexpressed in both SAP tissues and cells. CREB directly bound to the promoter of HDAC2 and activated its expression. Overexpressed CREB or HDAC2 inhibited proliferation and promoted apoptosis of cardiomyocytes. Suppression of CREB inhibited the HDAC2/TLR4/NF-κB cascade to promote proliferation and inhibit apoptosis of cardiomyocytes. The in vitro results were validated in vivo experiments. Coherently, suppression of CREB can inhibit HDAC2/TLR4/NF-κB cascade to promote cardiomyocyte proliferation, thus ameliorating SAP-induced myocardial injury.
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http://dx.doi.org/10.1007/s10753-021-01441-yDOI Listing
March 2021

Predicting gastric cancer outcome from resected lymph node histopathology images using deep learning.

Nat Commun 2021 03 12;12(1):1637. Epub 2021 Mar 12.

Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

N-staging is a determining factor for prognostic assessment and decision-making for stage-based cancer therapeutic strategies. Visual inspection of whole-slides of intact lymph nodes is currently the main method used by pathologists to calculate the number of metastatic lymph nodes (MLNs). Moreover, even at the same N stage, the outcome of patients varies dramatically. Here, we propose a deep-learning framework for analyzing lymph node whole-slide images (WSIs) to identify lymph nodes and tumor regions, and then to uncover tumor-area-to-MLN-area ratio (T/MLN). After training, our model's tumor detection performance was comparable to that of experienced pathologists and achieved similar performance on two independent gastric cancer validation cohorts. Further, we demonstrate that T/MLN is an interpretable independent prognostic factor. These findings indicate that deep-learning models could assist not only pathologists in detecting lymph nodes with metastases but also oncologists in exploring new prognostic factors, especially those that are difficult to calculate manually.
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http://dx.doi.org/10.1038/s41467-021-21674-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954798PMC
March 2021

[Clinical outcomes of radial artery as the second arterial conduit in coronary artery bypass].

Zhonghua Wai Ke Za Zhi 2021 Apr 1;59(4):293-297. Epub 2021 Apr 1.

Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing First Hospital, Nanjing Cardiovascular Hospital, Nanjing 210006, China.

To examine the clinical experience and outcomes of coronary artery bypass grafting (CABG) using radial artery as the second arterial graft. Totally 585 patients in whom both left internal thoracic artery and radial artery as arterial conduits were used in CABG in Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University from April 2008 to August 2019 were consecutively enrolled. There were 436 males and 149 females, aging (63±10) years (range: 36 to 86 years). There were 40.7% (238/585) of patients had diabetes and 75.6% (442/585) of them had multivessel disease (two-vessel or three-vessel diseases). From January 2017, transit time flow measurement was performed on every patient. Demographic and perioperative data were retrospectively collected, as well as follow-up data for patients who underwent CABG from January 2014 to August 2019. Analysis were made on their early and late outcomes. 81.9%(479/585) Most patients in this cohort (81.9%) received on-pump CABG and 11 patients had intraoperative intro-aortic balloon counterpulsation (prior to CABG) support. Forty-three patients had concomitant valve procedures. The number of distal anastomosis was 3.6±0.9 (range: 2 to 6) and number of arterial distal anastomosis was 2.1±0.3. Radial artery was anastomosed to left obtuse marginal artery in 95.8% (560/585) patients. All target vessels for radial artery conduit had significant proximal stenosis (>70%) and 72.5% (424/585) of target vessels had proximal stenosis which was >90%. Intraoperative transit-time flow measurement of 151 cases showed that radial artery conduits had a flow of (29.8±10.2) ml/minutes (range: 10 to 150 ml/min), and pulsatility index of 2.5±1.4 (range: 0.7 to 5.0). There was no operative death. Two in-hospital death occurred more than 30 days after index surgery. There was no perioperative myocardial infarction. There were 188 patients who received CABG from January 2014 to August 2019 followed-up for a median duration of 3.2 years. There were two noncardiac death. No patient had myocardial infarction or to receive myocardial revascularization. Radial artery as the second arterial conduit is a safe and effective strategy for CABG. Good selection of target vessel and intraoperative transit-time flow measurement may help achieve good patency, as well as the short and mid-term outcome.
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http://dx.doi.org/10.3760/cma.j.cn112139-20200220-00101DOI Listing
April 2021

Fully integrated protein absolute quantification platform for analysis of multiple tumor markers in human plasma.

Talanta 2021 May 14;226:122102. Epub 2021 Jan 14.

National Chromatographic Research and Analysis Center, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, 116023, China.

In this study, we developed a fully integrated protein absolute quantification platform for simultaneous analysis of multiple tumor markers in human plasma, by which multiple target proteins (alpha-fetoprotein, prostate-specific antigen, carcino-embryonic antigen and mucin-1) were firstly enriched by aptamers immobilized capillary column using graphene oxide modified polymer microsphere as the separation matrix, and then the eluted target proteins were online denatured, reduced, desalted and digested by our developed fully automated sample treatment device (FAST), finally the resulting peptides were analyzed by parallel reaction monitoring (PRM) on LTQ-orbitrap velos mass spectrometry. Compared to traditional ELISA assay, the platform exhibited significant advantages such as short analysis time, low limit of detection, and ease of automation. Furthermore, our developed platform was also applied in the absolute quantification of tumor markers from clinical human plasma samples, and the results were comparable to those obtained by clinical immunoassay. All the results demonstrated that such a platform could provide a promising tool for achieving high sensitivity, high accuracy, and high throughput detection of disease related protein markers in the routine physical examination and clinical disease diagnosis.
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http://dx.doi.org/10.1016/j.talanta.2021.122102DOI Listing
May 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo.

Nat Nanotechnol 2021 Jun 18;16(6):708-716. Epub 2021 Feb 18.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China.

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.
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http://dx.doi.org/10.1038/s41565-021-00856-wDOI Listing
June 2021

Laparoscopic assisted hydrocelectomy of the canal of Nuck: a case report.

Surg Case Rep 2021 Feb 18;7(1):52. Epub 2021 Feb 18.

Department of Surgery, Sapporo Higashi Tokushukai Hospital, 3-1, N-33, E-14, Higahi-ku, Sapporo, Hokkaido, 0650033, Japan.

Background: Accurate diagnosis and complete resection of hydrocele of canal of Nuck (HCN) is still a challenge for surgeons.

Case Presentation: A 28-year-old woman presented with a suspected inguinal hernia due to swelling in her right groin and was introduced for surgical treatment. Computed tomography scan revealed local cyst formation in the right groin and eliminated intestinal incarceration. In order to further confirm the diagnosis, we used laparoscopic exploration; after excluding a combined hernia, HCN was surgically removed using a conventional anterior peritoneal approach and a mesh patch repair was not needed. Postoperative pathology results showed no endometriosis or malignancy.

Conclusions: Laparoscopic assisted anterior approach provides both an accurate intraoperative diagnosis and a quick complete resection of HCN; it is the preferred treatment for women of childbearing age with pure HCN.
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http://dx.doi.org/10.1186/s40792-021-01137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892654PMC
February 2021

Low expression of GSTP1 in the aqueous humour of patients with primary open-angle glaucoma.

J Cell Mol Med 2021 Mar 17;25(6):3063-3079. Epub 2021 Feb 17.

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.

Primary open-angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high-resolution, label-free, liquid chromatography-tandem mass spectrometry-based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up-regulated proteins and 49 down-regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle-mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down-regulated expression of glutathione S-transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme-linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox-related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.
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http://dx.doi.org/10.1111/jcmm.16361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957170PMC
March 2021

A Destiny for Degradation: Interplay between Cullin-RING E3 Ligases and Autophagy.

Trends Cell Biol 2021 Jun 8;31(6):432-444. Epub 2021 Feb 8.

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Faculty of Health Sciences, University of Macau, Macau, China. Electronic address:

Autophagy and the ubiquitin-proteasome system (UPS) are two major pathways for protein degradation. The cullin-RING E3 ligases (CRLs) are the largest E3 ligase family and have key biological functions in maintaining protein homeostasis. We provide an updated review of the interactions between CRLs and autophagy, focusing on the regulatory effects of CRLs on the core autophagy machinery that consists of several autophagy-related protein (ATG) complexes and their key upstream signaling pathways. The involvement of such functional interactions in health and disease is also discussed. Understanding the role of CRLs in autophagy is helpful for the development of therapeutic strategies for diseases in which CRLs and autophagy are dysregulated, such as cancer and neurodegenerative conditions.
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http://dx.doi.org/10.1016/j.tcb.2021.01.005DOI Listing
June 2021