Publications by authors named "Yu Fan"

900 Publications

Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Immunol 2021 3;12:663602. Epub 2021 Sep 3.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Background: A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs).

Methods: MEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy.

Results: Twenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10-0.31; P<0.01) and malignancy (RR 0.74; 95%CI 0.55-0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of acute rejection (RR 1.58; 95%CI 1.22-2.04; P<0.01), infection (RR 1.55; 95%CI 1.01-1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34-2.59; P<0.01), leukopenia (RR 1.56; 95%CI 1.27-1.91; P<0.01), acne (RR 6.43; 95%CI 3.43-12.04; P<0.01), and mouth ulcer (RR 11.70; 95%CI 6.18-22.17; P<0.01) were higher in the mTORi group. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75-3.63; P<0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis/tubular atrophy.

Conclusions: Posttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.
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http://dx.doi.org/10.3389/fimmu.2021.663602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446650PMC
September 2021

Interleukin-1 β as Clinically Predictive Risk Marker for Recurrent Pregnancy Loss in Women Positive for Antinuclear Antibody.

Int J Clin Pract 2021 Sep 19:e14887. Epub 2021 Sep 19.

The Reproductive Medical Center, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

Aims: Antinuclear antibody (ANA) was found to be associated with recurrent pregnancy loss (RPL). This study was designed to explore the immunological predictive indicators of RPL in women with positive ANA.

Methods: A retrospective case-control study in a university hospital from March 2020 to January 2021 was performed, including 56 cases of women with RPL and 56 controls matched for age, all of which were positive for ANA. Levels of cytokines, lymphocyte subsets, immune globulin and complement in peripheral blood among two groups were compared. Statistical analyses in this study were performed using SPSS 25.0.

Results: The level of IL-1β was higher in RPL women compared to controls according to univariable analysis and multivariable regression logistic analysis [7.67 (5.86-11.35) vs. 5.00 (5.00-5.00), P=0.000]. After the cut-off value of IL-1β was set as 5.66 pg/ml, the prevalence of RPL was significantly elevated in the high IL-1β group as compared to the low IL-1β group (P<0.05). The sensitivity and specificity of IL-1β predicting RPL in ANA-positive women were 76.8% and 91.1%, respectively.

Conclusion: Increased IL-1β may play roles in the occurrence of RPL among women with positive ANA. The level of the IL-1β have the potential to be predictive indicator of RPL in women with positive ANA.
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http://dx.doi.org/10.1111/ijcp.14887DOI Listing
September 2021

The influence of rhein on the absorption of rehmaionoside D: In vivo, in situ, in vitro, and in silico studies.

J Ethnopharmacol 2021 Sep 15:114650. Epub 2021 Sep 15.

Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China; Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, Xianyang, 712046, China. Electronic address:

Ethnopharmacological Relevance: In traditional Chinese Medicine, Rehmannia glutinosa (Gaertn.) DC., as the principle herb of ShengDiHuang Decotion, has the effect of cooling blood and hemostasis, and tonifying the yin and kidney. Rheum L., as adjuvant herbs, assist Rehmannia glutinosa (Gaertn.) DC. to promote blood circulation to remove blood stasis.

Aim Of Study: To study the mechanism of Rhein involved in the promotion of Rehmannioside D absorption by pharmacokinetic studies, single-pass intestinal perfusion, Caco-2 cell models, molecular docking technique and western blotting.

Materials And Methods: Initially, the intestinal absorption of Rehmannioside D in the presence or absence of Rhein was conducted through pharmacokinetic studies. Thereafter, the intestinal absorption of Rehmannioside D and Rhein was studied using the single-pass intestinal perfusion and Caco-2 cell models. Finally, using molecular docking technique and western blotting.

Results: We found that the promotion of Rehmannioside D absorption by Rhein was mediated by breast cancer resistance and multidrug resistance-associated protein 2, thereby affecting the permeability of the intestinal epithelium. Additionally, Rhein and Rehmannioside D can competitively bind to breast cancer resistance and multidrug resistance-associated protein 2, and that Rhein inhibits the expression of breast cancer resistance and multidrug resistance-associated protein 2 in the ileum to promote the intestinal absorption of Rehmannioside D.

Conclusion: This study reveals the mechanisms associated with the Rhein-mediated promotion of Rehmannioside D absorption and provides a basis for further exploring the synergistic effect of Rehmannia glutinosa (Gaertn.) DC and rhubarb.
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http://dx.doi.org/10.1016/j.jep.2021.114650DOI Listing
September 2021

Circular RNAs' cap-independent translation protein and its roles in carcinomas.

Mol Cancer 2021 Sep 15;20(1):119. Epub 2021 Sep 15.

Cancer Institue, Affiliated People's Hospital of Jiangsu University, No 8, Dianli Road, Zhenjiang, Jiangsu Province, 212002, People's Republic of China.

Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.
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http://dx.doi.org/10.1186/s12943-021-01417-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442428PMC
September 2021

Use of a rapid human primary cell-based disease screening model, to compare next generation products to combustible cigarettes.

Curr Res Toxicol 2021 17;2:309-321. Epub 2021 Aug 17.

Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL UK.

A growing number of public health bodies, regulators and governments around the world consider electronic vapor products a lower risk alternative to conventional cigarettes. Of critical importance are rapid new approach methodologies to enable the screening of next generation products (NGPs) also known as next generation tobacco and nicotine products. In this study, the activity of conventional cigarette (3R4F) smoke and a range of NGP aerosols (heated tobacco product, hybrid product and electronic vapor product) captured in phosphate buffered saline, were screened by exposing a panel of human cell-based model systems using Biologically Multiplexed Activity Profiling (BioMAP® Diversity PLUS® Panel, Eurofins Discovery). Following exposure, the biological activity for a wide range of biomarkers in the BioMAP panel were compared to determine the presence of toxicity signatures that are associated with specific clinical findings. NGP aerosols were found to be weakly active in the BioMAP Diversity PLUS Panel (≤3/148 biomarkers) whereas significant activity was observed for 3R4F (22/148 biomarkers). Toxicity associated biomarker signatures for 3R4F included immunosuppression, skin irritation and thrombosis, with no toxicity signatures seen for the NGPs. BioMAP profiling could effectively be used to differentiate between complex mixtures of cigarette smoke or NGP aerosol extracts in a panel of human primary cell-based assays. Clinical validation of these results will be critical for confirming the utility of BioMAP for screening NGPs for potential adverse human effects.
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http://dx.doi.org/10.1016/j.crtox.2021.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408431PMC
August 2021

Prevalence of vitamin D deficiency and impact on clinical outcomes after kidney transplantation: a systematic review and meta-analysis.

Nutr Rev 2021 Sep 2. Epub 2021 Sep 2.

Urology Department, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China.

Context: The prevalence of vitamin D deficiency (VDD) and its impact on clinical outcomes after kidney transplant (KT) remain poorly defined.

Objectives: We conducted a meta-analysis to evaluate the impact of early VDD on clinical outcomes after KT.

Data Sources: Electronic databases (PubMed, Embase, Web of Science, and The Cochrane Library) were systematically searched for eligible publications up to April 30, 2020.

Data Extraction: Relative risk was presented as hazard ratios (HRs) or odds ratios (ORs) and 95%CIs for dichotomous outcomes. Mean difference (MD) and 95%CIs were presented for continuous outcomes.

Results: A total of 28 studies (13 prospective and 15 retrospective) were included. VDD was common early after KT, with a prevalence of 52% (95%CI: 41%-64%) at transplant, 34% (95%CI: 17%-51%) at 3 months, and 23% (95%CI: 10%-35%) at 6 months. Early VDD was associated with higher mortality rate after KT (HR, 1.56; 95%CI: 1.32-1.84; P < 0.001). In addition, early VDD led to higher risk of bacterial infection (OR, 1.82; 95%CI: 1.40-2.36; P < 0.001), BK polyomavirus infection (OR, 2.11, 95%CI: 1.23-3.61; P = 0.006), and cytomegalovirus infection (OR, 1.69; 95%CI: 1.24-2.31; P = 0.001). Early VDD increased the risk of acute rejection as well (HR, 2.28; 95%CI: 1.57-3.30; P < 0.001). Recipients with early VDD had lower estimated glomerular filtration rates (mean difference: -5.06; 95%CI: -7.28 to 2.83 mL/min; P < 0.001). Sensitivity analyses showed good stability of the pooled results.

Conclusion: VDD was common early after KT and associated with higher risk of death and adverse outcomes.
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http://dx.doi.org/10.1093/nutrit/nuab058DOI Listing
September 2021

A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.

Signal Transduct Target Ther 2021 Aug 31;6(1):325. Epub 2021 Aug 31.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-β (Aβ) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including APP, PSEN1, and PSEN2 impair a variety of pathways, including protein processing, axonal transport, and metabolic homeostasis. Here we identified a missense variant rs117916664 (c.896T>C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (ACAA1) gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the Aβ pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.
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http://dx.doi.org/10.1038/s41392-021-00748-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408221PMC
August 2021

Selective Extraction and Complexation Studies for Thorium(IV) with Bis-triamide Extractants: Synthesis, Solvent Extraction, EXAFS, and DFT.

Inorg Chem 2021 Sep 1;60(18):14212-14220. Epub 2021 Sep 1.

College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.

Three octyl-extended bis-triamide extractants (-) were designed and synthesized for the selective solvent extraction of Th(IV) over U(VI) in a kerosene-HNO system. and exhibited good extraction property and selectivity toward Th(IV) over U(VI) and reached extraction equilibrium within 10 min. In a wide range of a HNO concentration from 0.1 to 3.0 M, the separation factor of Th(IV) over U(VI) (SF) of and ranged from 12.1 ± 1.6 to 123.0 ± 20.2 and 15.2 ± 2.4 to 88.1 ± 14.9, respectively. Slope analysis indicated that Th(IV) was extracted as different species under different HNO concentrations, in which the slopes were 2.08 ± 0.20, 1.61 ± 0.03, and 1.54 ± 0.03 for and 2.37 ± 0.22, 2.07 ± 0.17, and 1.76 ± 0.18 for under 0.1, 1.0, and 3.0 M HNO, respectively. A continuous variation method (Job plot) illustrated a 1.5:1 ligand/thorium (L/Th) ratio in a methanol phase, indicating that / and Th(IV) could form mixed 1:1 and 2:1 L/Th extracted complexes. Extended X-ray absorption fine structure (EXAFS) and density functional theory (DFT) calculations revealed that the extracted complexes of and with Th during the extraction process at 0.1 M HNO were [2L1·Th·3(NO)] and [2L2·Th·3(NO)].
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http://dx.doi.org/10.1021/acs.inorgchem.1c01660DOI Listing
September 2021

The effect of postmastectomy radiation therapy on high-risk patients with T1-2N0 breast cancer.

Breast 2021 Aug 20;60:1-5. Epub 2021 Aug 20.

Department of Head, Neck and Mammary Gland Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: The prognostic impact of postmastectomy radiation therapy (PMRT) on high-risk patients with T1-2N0 breast cancer is controversial. We aimed to investigate the effect of PMRT on high-risk patients with T1-2N0 breast cancer.

Methods: A total of 3439 patients diagnosed with T1-2N0 breast cancer who received mastectomy between 2000 and 2016 in our institute were retrospectively analyzed. Leveraging the Fine and Gray competing risks regression in unirradiated patients, risk factors of locoregional recurrence (LRR) were identified. All patients were stratified into high-risk (3 or 4 risk factors) and low-risk (no more than 2 risk factors) groups. The prognostic effect of PMRT was estimated in two subgroups. This subgroup analysis was also performed in patients with T2N0 breast cancer.

Results: The median follow-up was 89 months. The 5-year cumulative incidence of LRR was 2.2% in unirradiated patients. Tumor size, estrogen receptor (ER) status, histologic grade and lymphovascular invasion (LVI) were identified as independent risk factors of LRR. In the high-risk group, PMRT was correlated with a 8.3% risk reduction of 5-year LRR, 7.8% risk reduction of 5-year distant recurrence (DR), and 6.4% risk reduction of 5-year breast cancer mortality (BCM), whereas it was not correlated with LRR, DR, or BCM in low-risk group. In patients with T2N0 breast cancer, PMRT was associated with decreased LRR, DR and BCM in high-risk group, other than low-risk group.

Conclusions: PMRT presented heterogenous effect on patients with T1-2N0 breast cancer. Patients at high risk of LRR were more likely to benefit from PMRT.
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http://dx.doi.org/10.1016/j.breast.2021.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399378PMC
August 2021

Chromosomal Characterization of Revealed by Oligo-FISH.

Int J Mol Sci 2021 Aug 9;22(16). Epub 2021 Aug 9.

National Engineering Research Center for Sugarcane, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Sugarcane is of important economic value for producing sugar and bioethanol.   (old name:  ) is an intergeneric wild species of sugarcane that has desirable resistance traits for improving sugarcane varieties. However, the scarcity of chromosome markers has hindered the cytogenetic study of . Here we applied maize chromosome painting probes (MCPs) to identify chromosomes in sorghum and using a repeated fluorescence in situ hybridization (FISH) system. Sequential FISH revealed that these MCPs can be used as reliable chromosome markers for , even though has diverged from maize over 18 MYs (million years). Using these MCPs, we identified chromosomes based on their sequence similarity compared to sorghum and labeled them 1 through 10. Then, the karyotype of was established by multiple oligo-FISH. Furthermore, FISH results revealed that 5S rDNA and 35S rDNA are localized on chromosomes 5 and 6, respectively, in . Altogether, these results represent an essential step for further cytogenetic research of in sugarcane breeding.
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http://dx.doi.org/10.3390/ijms22168539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395171PMC
August 2021

Effect of Pyrazosulfuron-Methyl on the Photosynthetic Characteristics and Antioxidant Systems of Foxtail Millet.

Front Plant Sci 2021 5;12:696169. Epub 2021 Aug 5.

State Key Laboratory of Sustainable Dryland Agriculture (in Preparation), College of Agronomy, Shanxi Agricultural University, Shanxi, China.

Foxtail millet ( L.) plays a principal role in food security in Africa and Asia, but it is sensitive to a variety of herbicides. This study was performed to clarify whether pyrazosulfuron-methyl can be used in foxtail millet fields and the effect of pyrazosulfuron-methyl on the photosynthetic performance of foxtail millet. Two foxtail millet varieties (Jingu 21 and Zhangzagu 10) were subjected to five doses (0, 15, 30, 60, and 120 g ai ha) of pyrazosulfuron-methyl in pot and field experiments. The plant height, leaf area, stem diameter, photosynthetic pigment contents, gas exchange parameters, chlorophyll fluorescence parameters, antioxidant enzyme activities, and antioxidant contents at 7 and 15 days after pyrazosulfuron-methyl application, and the yield of foxtail millet were measured. The results suggested that pyrazosulfuron-methyl inhibited the growth of foxtail millet and reduced the photosynthetic pigment contents, photosynthetic rate, and photosynthetic system II activity. Similarly, pyrazosulfuron-methyl decreased the antioxidant enzyme activities and antioxidant contents. These results also indicated that the toxicity of pyrazosulfuron-methyl to foxtail millet was decreased gradually with the extension of time after application; however, the foxtail millet yield was still significantly reduced. Therefore, pyrazosulfuron-methyl is not recommended for application in foxtail millet fields.
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http://dx.doi.org/10.3389/fpls.2021.696169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375152PMC
August 2021

Deciphering Neurodegenerative Diseases Using Long-Read Sequencing.

Neurology 2021 Aug 13;97(9):423-433. Epub 2021 Aug 13.

From the Department of Neurology (Y.S., L.F., C.S., T.W., H.Z., H.L., S.Z., Z.H., Y.F., Y.D., J.Y., C.M., Y.X.), The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, P. R. China; The Academy of Medical Sciences of Zhengzhou University (Y.S., L.F., C.S., T.E., H.Z., H.L., S.Z., Z.H., Y.F., Y.D., C.M.), Zhengzhou University,Henan, P. R. China; Henan Key Laboratory of Cerebrovascular Diseases (Y.S., L.F., C.S., H.Z., H.L., S.Z., Z.H., Y.F., Y.D., J.Y., C.M., Y.X.), The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, P. R. China; Sino-British Research Centre for Molecular Oncology (C.S., C.M.), National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Henan, P. R. China; and Institute of Neuroscience (J.W., Y.X.), Zhengzhou University, Henan, P. R. China.

Neurodegenerative diseases exhibit chronic progressive lesions in the central and peripheral nervous systems with unclear causes. The search for pathogenic mutations in human neurodegenerative diseases has benefited from massively parallel short-read sequencers. However, genomic regions, including repetitive elements, especially with high/low GC content, are far beyond the capability of conventional approaches. Recently, long-read single-molecule DNA sequencing technologies have emerged and enabled researchers to study genomes, transcriptomes, and metagenomes at unprecedented resolutions. The identification of novel mutations in unresolved neurodegenerative disorders, the characterization of causative repeat expansions, and the direct detection of epigenetic modifications on naive DNA by virtue of long-read sequencers will further expand our understanding of neurodegenerative diseases. In this article, we review and compare 2 prevailing long-read sequencing technologies, Pacific Biosciences and Oxford Nanopore Technologies, and discuss their applications in neurodegenerative diseases.
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http://dx.doi.org/10.1212/WNL.0000000000012466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408508PMC
August 2021

Two new toxic yellow species from China: morphological characteristics, phylogenetic analyses and toxin detection.

MycoKeys 2021 3;81:185-204. Epub 2021 Aug 3.

College of Life Sciences, Hunan Normal University, Changsha, Hunan 410006, China Hunan Normal University Changsha China.

Some species of caused neurotoxic poisoning after consumption around the world. However, there are a large number of species in this genus that have not been studied for their toxicity or toxin content. In this study, we report two new toxic yellow species from China based on morphological characteristics, phylogenetic analyses and toxin detection. Among the two species, is reported as a newly recorded species of China. We also describe a new species, , which is morphologically similar to . The new species is characterized by its ochraceous squarrose pileus, distinctly annulate cortina on the stipe, nodulose basidiospores and thick-walled pleurocystidia. Muscarine in the fruitbodies was detected by UPLC-MS/MS, the content in and were 136.4 ± 25.4 to 1683.0 ± 313 mg/kg dry weight and 31.2 ± 5.8 to 101.8 ± 18.9 mg/kg dry weight, respectively.
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http://dx.doi.org/10.3897/mycokeys.81.68485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355026PMC
August 2021

Studying the pathological and biochemical features in breast cancer progression by confocal Raman microspectral imaging of excised tissue samples.

J Photochem Photobiol B 2021 Sep 5;222:112280. Epub 2021 Aug 5.

Imaging Unit - Integrative Oncology Department, BC Cancer Research Center, Vancouver, BC V5Z 1L3, Canada. Electronic address:

Confocal Raman microspectral imaging (CRMI) has been used to detect the spectra-pathological features of ductal carcinoma in situ (DCIS) and lobular hyperplasia (LH) compared with the heathy (H) breast tissue. A total of 15-20 spectra were measured from healthy tissue, LH tissue, and DCIS tissue. One-way ANOVA and Tukey's honest significant difference (HSD) post hoc multiple tests were used to evaluate the peak intensity variations in all three tissue types. Besides that, linear discrimination analysis (LDA) algorithm was adopted in combination with principal component analysis (PCA) to classify the spectral features from tissues at different stages along the continuum to breast cancer. Moreover, by using the point-by-point scanning methodology, spectral datasets were obtained and reconstructed for further pathologic visualization by multivariate imaging methods, including K-mean clustering analysis (KCA) and PCA. Univariate imaging of individual Raman bands was also used to describe the differences in the distribution of specific molecular components in the scanning area. After a detailed spectral feature analysis from 800 to 1800 cm and 2800 to 3000 cm for all the three tissue types, the histopathological features were visualized based on the content and structural variations of lipids, proteins, phenylalanine, carotenoids and collagen, as well as the calcification phenomena. The results obtained not only allowed a detailed Raman spectroscopy-based understanding of the malignant transformation process of breast cancer, but also provided a solid spectral data support for developing Raman based breast cancer clinical diagnostic techniques.
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http://dx.doi.org/10.1016/j.jphotobiol.2021.112280DOI Listing
September 2021

Effect of Osmotic Stress on the Growth, Development and Pathogenicity of .

Front Microbiol 2021 23;12:706349. Epub 2021 Jul 23.

State Key Laboratory of North China Crop Improvement and Regulation, Baoding, China.

Osmotic stress is a severe condition frequently encountered by microorganisms; however, there is limited knowledge on the influence of hyperosmotic stress on the growth, development and pathogenicity of phytopathogenic fungi. Here, three osmotic conditions (0.4 M NaCl, 0.4 M KCl, and 0.6 M sorbitol supplemented in potato dextrose agar medium) were used to identify the effect of osmotic stress on the growth, development and pathogenicity of which is a plant pathogenic fungus and causes northern corn leaf blight disease in maize, sorghum, and related grasses. In osmotic stress, the growth rate of mycelium was decreased, and the number of vesicular structures and flocculent secretion outside the hypha cell wall were significantly increased. The qRT-PCR results showed that the osmotic stress quickly activated the HOG-MAPK pathway, up-regulated the expression of the downstream genes, and these genes were most highly expressed within 30 min of exposure to osmotic stress. Furthermore, the germination rate and the yield of conidia were significantly higher under osmotic stress than in the control. A pathogenicity analysis confirmed that pathogenicity of the conidia which were cultured under osmotic stress was significantly enhanced. By analyzing the knock-out mutants of an osmotic stress responsed gene , an aquaglyceroporin downstream of the HOG-MAPK pathway, we found that was involved in the formation of appressorium and penetration peg, which affected the penetration ability of . In summary, our work explained the correlation between osmotic stress and growth, development, and pathogenicity in .
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http://dx.doi.org/10.3389/fmicb.2021.706349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342955PMC
July 2021

Scalable Asymmetric Synthesis of the All Triamino Cyclohexane Core of BMS-813160.

J Org Chem 2021 Aug 6. Epub 2021 Aug 6.

Analytical Strategy & Operations, Bristol Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903-0191, United States.

BMS-813160 is a pharmaceutical entity currently in development at Bristol Myers Squibb. Its defining structural feature is a unique chiral all triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis strategies for chemotypes similar to the target molecule, but a streamlined approach amenable for longer-term supply was necessary. A new synthetic route was conceptualized, experimentally investigated, and determined to meet the criteria for efficiency that addressed key limitations of previous approaches. Adopting/optimizing the Trost asymmetric allylic amination desymmetrization methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich-aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to fulfill long-term supply requirements.
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http://dx.doi.org/10.1021/acs.joc.1c01162DOI Listing
August 2021

Pulmonary Adenofibroma: Clinicopathological and Genetic Analysis of 7 Cases With Literature Review.

Front Oncol 2021 19;11:667111. Epub 2021 Jul 19.

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

Introduction: Pulmonary adenofibroma (PAF), characterized by biphasic differentiation composed of gland-like space lined by respiratory epithelium and stromal spindle cells, is a rare benign tumor of the lung. PAF was reported infrequently and inconsistently with diagnostic criteria and withstood higher risk of misdiagnosis as solitary fibrous tumors (SFTs) due to their morphological resemblance. In this study, we report seven cases of PAF with gene sequencing results and summarize the data of previous literature.

Materials And Methods: Seven cases of PAF with surgically resection samples were collected from Pathology department of West China Hospital, Sichuan University between 2009 to 2020. Immunohistochemical studies were performed in all cases and 3 cases underwent a 425-gene panel next-generation sequencing (NGS).

Results: Five female and two male patients were included in this study, with an average age of 51 years. All the patients were asymptomatic, and the lesion was identified on routine chest radiography. The tumor size measured by computed tomography (CT) ranged from 0.5 to 2.7 cm. Gland-like structures were mostly positive for glandular epithelium markers. The spindle cells in stroma expressed Desmin, SMA, ER and PR in 3 of 7 cases. No well-recognized molecular abnormalities can be identified by NGS in the 3 cases. To date, all the patients are alive, with no evidence of recurrence and metastasis.

Conclusion: PAF is a unique benign pulmonary tumor with low incidence. Biphasic morphology, IHC stains along with molecular detection is of great significance to make a clear diagnosis.
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http://dx.doi.org/10.3389/fonc.2021.667111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328424PMC
July 2021

Trends of the response-relationship between net anthropogenic nitrogen and phosphorus inputs (NANI/NAPI) and TN/TP export fluxes in Raohe basin, China.

Chemosphere 2021 Jul 24;286(Pt 1):131662. Epub 2021 Jul 24.

Key Laboratory of Poyang Lake Environment and Resource Utilization, Ministry of Education, School of Resources Environmental and Chemical Engineering, Nanchang University, Nanchang, 330031, China.

The intensification of anthropogenic nitrogen (N) and phosphorus (P) inputs profoundly affects water environmental quality. Hence it is pivotal to clarify the response relationship between riverine TN/TP export and anthropogenic N/P inputs to provide strategies guidance in N/P management. Based on the variation of net anthropogenic N and P inputs (NANI/NAPI) in the Raohe basin from 1990 to 2018, we constructed the response relationship between NANI/NAPI and total nitrogen and phosphorus (TN/TP) export fluxes in the riverine, which successfully predicted N and P export at the basin scale management. We found N export ratio (ratio of TN export to NANI) increased with slight fluctuation and was mainly affected by the combined effects of Nfer (fertilizer N inputs) and Ndep (atmospheric N deposition) etc., while the decrease of P export ratio (ratio of TP export to NAPI) was mainly due to intensive retention effect of the soil and sediment induced by anthropogenic influence to P transportation process. These results indicate that the downstream aquatic systems take a high risk of increasing N load pressure and the basin systems suffer a danger from rising P load pressure. Therefore, it is recommended to concentrate more on downstream aquatic systems during the N management strategy implementation and pay closer attention to the whereabouts of P in the basin system.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131662DOI Listing
July 2021

Multi-endpoint analysis of human 3D airway epithelium following repeated exposure to whole electronic vapor product aerosol or cigarette smoke.

Curr Res Toxicol 2021 20;2:99-115. Epub 2021 Feb 20.

Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, United Kingdom.

Smoking is a cause of serious diseases in smokers including chronic respiratory diseases. This study aimed to evaluate the tobacco harm reduction (THR) potential of an electronic vapor product (EVP, blu™) compared to a Kentucky Reference Cigarette (3R4F), and assessed endpoints related to chronic respiratory diseases. Endpoints included: cytotoxicity, barrier integrity (TEER), cilia function, immunohistochemistry, and pro-inflammatory markers. In order to more closely represent the user exposure scenario, we have employed the 3D organotypic model of human airway epithelium (MucilAir™, Epithelix) for respiratory assessment. The model was repeatedly exposed to either whole aerosol of the EVP, or whole 3R4F smoke, at the air liquid interface (ALI), for 4 weeks to either 30, 60 or 90 puffs on 3-exposure-per-week basis. 3R4F smoke generation used the ISO 20778:2018 regime and EVP aerosol used the ISO 20768:2018 vaping regime. Exposure to undiluted whole EVP aerosol did not trigger any significant changes in the level of pro-inflammatory mediators, cilia beating function, barrier integrity and cytotoxicity when compared with air controls. In contrast, exposure to diluted (1:17) whole cigarette smoke caused significant changes to all the endpoints mentioned above. To our knowledge, this is the first study evaluating the effects of repeated whole cigarette smoke and whole EVP aerosol exposure to a 3D lung model at the ALI. Our results add to the growing body of scientific literature supporting the THR potential of EVPs relative to combustible cigarettes and the applicability of the 3D lung models in human-relevant product risk assessments.
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http://dx.doi.org/10.1016/j.crtox.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320624PMC
February 2021

The use of human induced pluripotent stem cells to screen for developmental toxicity potential indicates reduced potential for non-combusted products, when compared to cigarettes.

Curr Res Toxicol 2020 Jun 15;1:161-173. Epub 2020 Nov 15.

Imperial Brands PLC, 121 Winterstoke Road, Bristol BS3 2LL, UK.

devTOX Predict (devTOX ) is a metabolomics biomarker-based assay that utilises human induced pluripotent stem (iPS) cells to screen for potential early stage embryonic developmental toxicity Developmental toxicity potential is assessed based on the assay endpoint of the alteration in the ratio of key unrelated biomarkers, ornithine and cystine (o/c). This work aimed to compare the developmental toxicity potential of tobacco-containing and tobacco-free non-combustible nicotine products to cigarette smoke. Smoke and aerosol from test articles were produced using a Vitrocell VC10 smoke/aerosol exposure system and bubbled into phosphate buffered saline (bPBS). iPS cells were exposed to concentrations of up to 10% bPBS. Assay sensitivity was assessed through a spiking study with a known developmental toxicant, allretinoic acid (ATRA), in combination with cigarette smoke extract. The bPBS extracts of reference cigarettes (1R6F and 3R4F) and a heated tobacco product (HTP) were predicted to have the potential to induce developmental toxicity, in this screening assay. The bPBS concentration at which these extracts exceeded the developmental toxicity threshold was 0.6% (1R6F), 1.3% (3R4F), and 4.3% (HTP) added to the cell media. Effects from cigarette smoke and HTP aerosol were driven largely by cytotoxicity, with the cell viability and o/c ratio dose-response curves crossing the developmental toxicity thresholds at very similar concentrations of added bPBS. The hybrid product and all the electronic cigarette (e-cigarette) aerosols were not predicted to be potential early developmental toxicants, under the conditions of this screening assay.
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http://dx.doi.org/10.1016/j.crtox.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320631PMC
June 2020

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics.

Respir Res 2021 Aug 3;22(1):216. Epub 2021 Aug 3.

Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.

Background: Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA.

Methods: Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells.

Results: NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV compared to EA. For all asthmatics, sputum IL-1β mRNA was positively correlated with protein expression. Sputum IL-1β mRNA and protein levels were negatively correlated to FEV improvement. After subgrouping, the correlation between IL-1β mRNA and FEV improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1β augmenting TGF-β1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors.

Conclusions: IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways.

Trial Registration: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).
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http://dx.doi.org/10.1186/s12931-021-01808-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336269PMC
August 2021

Design, synthesis, and biological evaluation of novel FXR agonists based on auraptene.

Bioorg Chem 2021 Jul 21;115:105198. Epub 2021 Jul 21.

Department of Pharmacy, Affiliated Hospital 4 of Nantong University, The First People's Hospital of Yancheng City, Yancheng, PR China. Electronic address:

Farnesoid X receptor (FXR) has been considered as an attractive target for metabolic disorder and liver injury, while many current FXR agonists suffer from undesirable side effects, such as pruritus. Therefore, it is urgent to develop new structure types different from current FXR agonists. In this study, a series of structural optimizations were introduced to displace the unstable coumarin and geraniol scaffolds of auraptene (AUR), a novel and safe FXR agonist. All of these efforts led to the identification of compound 14, a potent FXR agonist with nearly fourfold higher activity than AUR. Molecular modeling study suggested that compound 14 fitted well with binding pocket, and formed the key ionic bond with His291 and Arg328. In acetaminophen-induced acute liver injury model, compound 14 exerts better therapeutic effect than that of AUR, which highlighting its pharmacological potential in the treatment of drug-induced liver injury.
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http://dx.doi.org/10.1016/j.bioorg.2021.105198DOI Listing
July 2021

Proteomic study of Desulfovibrio ferrophilus IS5 reveals overexpressed extracellular multi-heme cytochrome associated with severe microbiologically influenced corrosion.

Sci Rep 2021 Jul 29;11(1):15458. Epub 2021 Jul 29.

Corporate Strategic Research, ExxonMobil Research and Engineering Company, 1545 Route 22 East, Annandale, NJ, 08801, USA.

Microbiologically influenced corrosion (MIC) is recognized as a considerable threat to carbon steel asset integrity in the oil and gas industry. There is an immediate need for reliable and broadly applicable methods for detection and monitoring of MIC. Proteins associated with microbial metabolisms involved in MIC could serve as useful biomarkers for MIC diagnosis and monitoring. A proteomic study was conducted using a lithotrophically-grown bacterium Desulfovibrio ferrophilus strain IS5, which is known to cause severe MIC in seawater environments. Unique proteins, which are differentially and uniquely expressed during severe microbial corrosion by strain IS5, were identified. This includes the detection of a multi-heme cytochrome protein possibly involved in extracellular electron transfer in the presence of the carbon steel. Thus, we conclude that this newly identified protein associated closely with severe MIC could be used to generate easy-to-implement immunoassays for reliable detection of microbiological corrosion in the field.
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http://dx.doi.org/10.1038/s41598-021-95060-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322314PMC
July 2021

Oncogenic roles of lncRNA BLACAT1 and its related mechanisms in human cancers.

Biomed Pharmacother 2020 Oct 17;130:110632. Epub 2020 Sep 17.

Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China. Electronic address:

Long non-coding RNAs (lncRNAs) play indispensable roles in mediating regulation of epigenetics, and their dysregulation is strongly associated with the initiation and progression of human cancers. Recently, lncRNA bladder cancer-associated transcript 1 (BLACAT1) has been observed to exert oncogenic effects on cancers, including glioma, breast cancer, lung cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, ovarian cancer, cervical cancer and osteosarcoma. Additional mechanical analyses have uncovered that lncRNA BLACAT1 is positively correlated with tumor stage, lymph node metastasis and distant metastasis of primary tumors via involvement with various cellular activities, thus leading to poor overall survival and progression-free survival (PFS). In this review, we generalize the oncogenic roles of BLACAT1 in multiple human cancers through correlation with clinical implications and cellular activities. Moreover, we forecast its potential clinical application as a novel biomarker and a promising therapeutic target for cancers.
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http://dx.doi.org/10.1016/j.biopha.2020.110632DOI Listing
October 2020

Dual-cation-doped MoSnanosheets accelerating tandem alkaline hydrogen evolution reaction.

Nanotechnology 2021 Aug 13;32(44). Epub 2021 Aug 13.

College of Physical Science and Technology, Institute of Optoelectronic Technology, Yangzhou University, Yangzhou 225002, People's Republic of China.

Molybdenum disulfide (MoS) nanosheets are promising candidates as earth-abundant and low-cost catalyst for hydrogen evolution reaction (HER). Nevertheless, compared with the benchmark Pt/C catalyst, the application of MoSnanosheets is limited to its relatively low catalytic activity, especially in alkaline environments. Here, we developed a dual-cation doping strategy to improve the alkaline HER performance of MoSnanosheets. The designed Ni, Co co-doped MoSnanosheets can promote the tandem HER steps simultaneously, thus leading to a much enhanced catalytic activity in alkaline solution. Density functional theory calculations revealed the individual roles of Ni and Co dopants in the catalytic process. The doped Ni is uncovered to be the active site for the initial water-cleaving step, while the Co dopant is conducive to the H desorbing by regulating the electronic structure of neighboring edge-S in MoS. The synergistic effect resulted by the dual-cation doping thus facilitates the tandem HER steps, providing an effective route to raise the catalytic performance of MoSmaterials in alkaline solution.
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http://dx.doi.org/10.1088/1361-6528/ac17c5DOI Listing
August 2021

Overexpression of aquaporin 2 in renal tubular epithelial cells alleviates pyroptosis.

Transl Androl Urol 2021 Jun;10(6):2340-2350

Urology Department, Urology Research Institute, West China Hospital, Sichuan University, Chengdu, China.

Background: Severe renal ischemia-reperfusion injury results in worse outcomes of kidney transplantation. Compared to the collecting duct, the proximal tubule is more likely to exhibit severe pyroptosis and damage during renal ischemia-reperfusion. Aquaporins were reported of having regulatory roles in pyroptosis. We explored whether aquaporin 2 overexpression in proximal tubular cells could alleviate ischemia-reperfusion injury related pyroptosis.

Methods: A renal ischemia-reperfusion model of mice was established, and human kidney 2 cells were treated with hypoxia-reoxygenation. Aquaporin 2 overexpression was achieved in human kidney 2 cells transfected with lentivirus, which were then cultured with murine cells. Renal tissues and serum of the mice, and human kidney 2 cells were subjected to histological, molecular, and biochemical examinations.

Results: Compared with the sham group, the renal function of the ischemia-reperfusion group was significantly decreased, and the tissue injury was severe and accompanied by more nuclear dissolved and necrosis. Besides, the expression of aquaporin 1-5 decreased significantly, while the expression of Toll-like receptor 4, caspase-1, kim-1 and interleukin 1β and 18 increased significantly in ischemia-reperfusion group. Similar results were observed in the human kidney 2 cells test. Overexpression of aquaporin 2 partially reversed the cell damage, pyroptosis, and molecular expression changes of human kidney 2 cells induced by hypoxia-reoxygenation.

Conclusions: Our findings suggest that aquaporin 2 overexpression can potentially reduce pyroptosis in proximal tubular cells, and thus might be a novel target for relieving pyroptosis and injury in renal ischemia-reperfusion injury.
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http://dx.doi.org/10.21037/tau-21-71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261442PMC
June 2021

Preparation and Characterization of Phosphoric Acid-Modified Biochar Nanomaterials with Highly Efficient Adsorption and Photodegradation Ability.

Langmuir 2021 Aug 21;37(30):9253-9263. Epub 2021 Jul 21.

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266033, China.

Phosphoric acid-modified biochar (PMBC) was prepared using biochar (BC) as the carbon source and phosphoric acid as the activating agent. The PMBC exhibited an ordered vessel structure after deashing treatment, but the sidewalls became much rougher, the polarity (O/C atomic ratio of BC = 0.2320 and O/C atomic ratio of PMBC = 0.1604) decreased, and the isoelectric points (PI of BC = 5.22 and PI of PMBC = 5.51) and specific surface area (SSA of BC = 55.322 m/g and SSA of PMBC = 62.285 m/g) increased. The adsorption characterization of the removal of sulfadiazine (SDZ) from PMBC was studied. The adsorption of SDZ by PMBC was in accordance with the Langmuir isotherm model and the pseudo-second-order kinetics model, and the adsorption thermodynamics were shown as Gibbs free energy < 0, an enthalpy change of 19.157 kJ/mol, and an entropy change of 0.0718 kJ/(K·mol). The adsorption of SDZ by PMBC was a complicated monolayer adsorption that was spontaneous, irreversible, and endothermic, and physical adsorption and chemical adsorption occurred simultaneously. The adsorption process was controlled by microporous capture, electrostatic interactions, hydrogen-bond interactions, and π-π interactions. [email protected] photocatalysts with different mass ratios between TiO and PMBC were prepared the sol-gel method. [email protected] exhibited both an ordered vessel structure (PMBC) and irregular particles (TiO), and it was linked Ti-O-C bonds. The optimal mass ratio between TiO and PMBC was 3:1. The removal of SDZ [email protected] was dependent on the coupling of adsorption and photocatalysis. The PMBC-enhanced photocatalytic performance of [email protected] resulted in a higher absorption of UV and visible light, greater generation of reactive oxygen species, high levels of adsorption of SDZ on PMBC, and the conjugated structure and oxygen-containing functional groups that promoted the separation efficiency of the hole-electron pairs.
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http://dx.doi.org/10.1021/acs.langmuir.1c01468DOI Listing
August 2021

Binding-Induced Fibrillogenesis Peptides Recognize and Block Intracellular Vimentin Skeletonization against Breast Cancer.

Nano Lett 2021 07 14;21(14):6202-6210. Epub 2021 Jul 14.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing 100190, People's Republic of China.

Life is recognized as a sophisticated self-assembling material system. Cancer involves the overexpression and improper self-assembly of proteins, such as cytoskeleton protein vimentin, an emerging target related to tumor metastasis. Herein, we design a binding-induced fibrillogenesis (BIF) peptide that in situ forms fibrous networks, blocking the improper self-assembly of vimentin against cancer. The BIF peptide can bind to vimentin and subsequently perform fibrillogenesis to form fibers on vimentin. The resultant peptide fibrous network blocks vimentin skeletonization and inhibits the migration and invasion of tumor cells. In mouse models of tumor metastasis, the volume of tumor and the number of lung metastases are markedly decreased. Moreover, the efficacy of BIF peptide (5 mg/kg) is much higher than small molecular antimetastasis drug withaferin A (5 mg/kg) as a standard, indicating that the BIF peptide shows advantages over small molecular inhibitors in blocking the intracellular protein self-assembly.
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http://dx.doi.org/10.1021/acs.nanolett.1c01950DOI Listing
July 2021

Tissue-specific 5-hydroxymethylcytosine landscape of the human genome.

Nat Commun 2021 07 12;12(1):4249. Epub 2021 Jul 12.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions.
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http://dx.doi.org/10.1038/s41467-021-24425-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275684PMC
July 2021

Asymmetric dimethylarginine level as biomarkers of cardiovascular or all-cause mortality in patients with chronic kidney disease: a meta-analysis.

Biomarkers 2021 Jul 27:1-7. Epub 2021 Jul 27.

Institute of Molecular Biology and Translational Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.

Background: Studies have yielded conflicting findings on the association of asymmetric dimethylarginine (ADMA) level with cardiovascular or all-cause mortality in patients with chronic kidney disease (CKD). This meta-analysis sought to evaluate the association of blood ADMA level with cardiovascular or all-cause mortality in CKD patients.

Materials And Methods: PubMed and Embase databases were comprehensively searched until September 9, 2020 for studies investigating the association of ADMA level with cardiovascular or all-cause mortality in CKD patients.

Results: Data were collected from nine prospective studies involving 6553 patients. The pooled adjusted risk ratio (RR) of all-cause mortality was 2.06 (95% confidence interval [CI] 1.43-2.96) for the highest versus the lowest ADMA level. Each 0.20 μmol/L ADMA increase was associated with 21% (95% CI 1.09-1.35) higher risk of all-cause mortality but not cardiovascular mortality (RR 1.07; 95% CI 0. 99-1.16). Subgroup analysis showed that each 0.20 μmol/L ADMA increase was significantly associated with all-cause mortality in end-stage renal disease (ESRD) patients (RR 1.22; 95% CI 1.05-1.41) but not in patients with stage 3 to 4 CKD (RR 1.16; 95% CI 0.86-1.56).

Conclusions: Elevated ADMA level is independently associated with higher risk of all-cause mortality in ESRD patients.
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http://dx.doi.org/10.1080/1354750X.2021.1954694DOI Listing
July 2021
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