Publications by authors named "Xi Hu"

143 Publications

A novel preparation of S-nZVI and its high efficient removal of Cr(VI) in aqueous solution.

J Hazard Mater 2021 08 20;416:125924. Epub 2021 Apr 20.

College of Environmental Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China. Electronic address:

The chitosan-stabilized biochar supported S-nZVI ([email protected]/S-nZVI) composite with low aggregation and superior antioxidation were successfully synthesized by liquid-phase reduction method for the outstanding removal of Cr(VI) from wastewater and characterized by SEM, BET, FTIR, XRD, and XPS. The optimized synthesis parameters of [email protected]/S-nZVI were determined as a 0.14 molar ratio of S/Fe and a 0.25 mass ratio of BC/Fe. The [email protected]/S-nZVI possessed a specific surface area of 199.246 m/g and an average pore size and pore volume of 1.186 nm and 0.272 cc/g. The [email protected]/S-nZVI could remain reductive activity after Cr(VI) removal and present a remarkable tolerance to the coexisting ions during Cr(VI) removal. The adsorption data were fitted well by the pseudo-second order model and the Langmuir model. The removal of Cr(VI) by [email protected]/S-nZVI was an exothermic process with prominent Cr(VI) removal capacities of 244.07 mg/g at 120 min and 221.84 mg/g at 15 min at 25 ℃. Further mechanism analysis proved that the binding of Cr(VI) to [email protected]/S-nZVI was mainly a synergistic effect of reduction and electrostatic attraction. Overall, these findings shed new light on the research of a novel S-nZVI compound and revealed the potential practical application of [email protected]/S-nZVI in the future heavy metal removal from wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125924DOI Listing
August 2021

Accurate Measurement of Agatston Score Using kVp-Independent Reconstruction Algorithm for Ultra-High-Pitch Sn150 kVp CT.

Korean J Radiol 2021 Aug 19. Epub 2021 Aug 19.

Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Objective: To investigate the accuracy of the Agatston score obtained with the ultra-high-pitch (UHP) acquisition mode using tin-filter spectral shaping (Sn150 kVp) and a kVp-independent reconstruction algorithm to reduce the radiation dose.

Materials And Methods: This prospective study included 114 patients (mean ± standard deviation, 60.3 ± 9.8 years; 74 male) who underwent a standard 120 kVp scan and an additional UHP Sn150 kVp scan for coronary artery calcification scoring (CACS). These two datasets were reconstructed using a standard reconstruction algorithm (120 kVp + Qr36d, protocol A; Sn150 kVp + Qr36d, protocol B). In addition, the Sn150 kVp dataset was reconstructed using a kVp-independent reconstruction algorithm (Sn150 kVp + Sa36d, protocol C). The Agatston scores for protocols A and B, as well as protocols A and C, were compared. The agreement between the scores was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. The radiation doses for the 120 kVp and UHP Sn150 kVp acquisition modes were also compared.

Results: No significant difference was observed in the Agatston score for protocols A (median, 63.05; interquartile range [IQR], 0-232.28) and C (median, 60.25; IQR, 0-195.20) ( = 0.060). The mean difference in the Agatston score for protocols A and C was relatively small (-7.82) and with the limits of agreement from -65.20 to 49.56 (ICC = 0.997). The Agatston score for protocol B (median, 34.85; IQR, 0-120.73) was significantly underestimated compared with that for protocol A ( < 0.001). The UHP Sn150 kVp mode facilitated an effective radiation dose reduction by approximately 30% (0.58 vs. 0.82 mSv, < 0.001) from that associated with the standard 120 kVp mode.

Conclusion: The Agatston scores for CACS with the UHP Sn150 kVp mode with a kVp-independent reconstruction algorithm and the standard 120 kVp demonstrated excellent agreement with a small mean difference and narrow agreement limits. The UHP Sn150 kVp mode allowed a significant reduction in the radiation dose.
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http://dx.doi.org/10.3348/kjr.2021.0050DOI Listing
August 2021

Effects of ecological environment and host genotype on the phyllosphere bacterial communities of cigar tobacco ( L.).

Ecol Evol 2021 Aug 21;11(16):10892-10903. Epub 2021 Jul 21.

College of Agronomy Hunan Agricultural University Changsha China.

Microorganisms of plant phyllosphere play an important role in plant health and productivity and are influenced by abiotic and biotic factors. In this study, we investigated the phyllosphere bacterial communities of three cigar tobacco varieties cultivated in Guangcun (GC) and Wuzhishan (WZS), Hainan, China. Metagenomic DNA was extracted from tobacco leaf samples and sequenced by 16S rDNA amplicon sequencing. Our results showed that bacterial communities of cigar tobacco phyllosphere in GC exhibited remarkably higher alpha diversity than that in WZS. There was slight effect of tobacco genotype variations on the alpha diversity in both cultivation sites, and beta diversity and structure of bacterial community were not influenced significantly by the cultivation sites and tobacco varieties. Statistical analyses of species diversity unraveled that the dominant species in bacterial communities of cigar tobacco phyllosphere among all these samples were phylogenetically affiliated to and . At the genus level, the most abundant microorganism was , followed by , unidentified_, and . Additionally, environmental conditions except for humidity were negatively correlated with the relative abundance of bacterial genera. Further analyses revealed that influence of site-specific factors on tobacco bacterial community was relatively higher than genotype-specific factors. In short, this study may contribute to the knowledge base of practical applications of bacterial inoculants for tobacco leaf production.
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http://dx.doi.org/10.1002/ece3.7861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366869PMC
August 2021

The effect of marital and insurance status on the survival of elderly patients with stage M1b colon cancer: a SEER-based study.

BMC Cancer 2021 Aug 5;21(1):891. Epub 2021 Aug 5.

Institute of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South, Hengyang, China.

Background: Colon cancer is largely implicated in elderly patients (age ≥ 60 years). The prognosis of patients diagnosed with the M1b stage is vastly poor. Marital and insurance status has been considered important prognostic factors in various cancer types. However, how these factors influence elderly patients with stage M1b colon cancer remains to be explored. This study aims to uncover the role of marital and insurance status in the survival of elderly patients with stage M1b colon cancer.

Methods: We retrieved data for patients diagnosed with stage M1b colon cancer between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis of the clinicopathological features, overall survival (OS), and cancer-specific survival (CSS) was based on the marital and insurance status, respectively.

Results: In sum, 5709 stage M1b colon cancer patients with complete information from SEER were enrolled for analysis. The OS and CSS of the Non-married group were poorer compared to that of the Married group. The OS and CSS of the Uninsured group were poorer than both of the Insured group and Medicaid group. However, OS was comparable between Uninsured group and Medicaid groups. The findings allude that marital and insurance status potentially impact the long-term survival of elderly patients with M1b colon cancer. The subgroup survival analyses revealed the lowest risk for death among the Insured Married group based on the comparison of the OS and CSS across all other groups. Moreover, Univariate and multivariate analyses revealed race, marital status, surgery, and chemotherapy as independent predictors for OS, whereas insurance status, surgery,and chemotherapy were independent predictors for CSS in elderly patients with M1b colon cancer.

Conclusion: The marital and insurance status greatly impact the survival of elderly patients with M1b colon cancer. Therefore, it is imperative to provide more support to this vulnerable patient group who are lonely and uninsured, particularly in the psychological and health insurance aspect.
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http://dx.doi.org/10.1186/s12885-021-08627-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340368PMC
August 2021

Exploring solutions to alleviate the regional water stress from virtual water flows in China.

Sci Total Environ 2021 Nov 16;796:148971. Epub 2021 Jul 16.

State Environmental Protection Key Laboratory of Environmental Planning and Policy Simulation, Chinese Academy of Environmental Planning, Beijing 100012, China; The Center for Beijing-Tianjin-Hebei Regional Environment and Ecology, Chinese Academy of Environmental Planning, Beijing 100012, China. Electronic address:

China has long faced an uneven distribution of physical water resources, which has been further exacerbated by the virtual water transfers embodied in the interregional trade. To alleviate such unfavorable influences of interregional virtual water flows on regional water scarcity, this paper first combined a multi-regional input-output model and a structural decomposition analysis to identify the major driving forces behind the changes in interregional virtual water flows from 2002 to 2012, and then conducted a scenario analysis to explore solutions for sustainable water resource management in China. Results indicated that the virtual water outflows from water-deficient developing regions (Northwest and Northeast) to water-abundant developed regions, such as East Coast and South Coast, have been increasingly intensified from 2002 to 2012. During the period, the final demand predominated the increase of virtual water transfers, while the improvement of water use efficiency dominated the decline in virtual water flows from 2002 to 2012. Results from the designed scenarios indicated that the negative impacts of interregional virtual water flows on the water stress can be effectively relieved, indicating the high priority of regional water use efficiency improvement, especially in water-starved regions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148971DOI Listing
November 2021

Downward aeration promotes static composting by affecting mineralization and humification.

Bioresour Technol 2021 Oct 14;338:125592. Epub 2021 Jul 14.

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

A composting experiment with sewage sludge and green waste was conducted to explore the effects of aeration directions (i.e., upward and downward) on static composting systems. The compost properties, including humification indexes and organic matter loss rate, and microbial diversity during the composting, were determined. Results showed that the downward aeration promoted the homogenization of temperature and moisture of the static composting system, thereby stimulating microbial metabolism and accelerating mineralization and humification. Microbial community profiles significantly changed among the composting phases. The humification dynamics were significantly correlated with the relative abundance of multiple microbial functional groups. However, no significant effects of aeration direction on the microbial community profiles were observed. The findings indicate that downward aeration is promising to improve the quality of static compost production, by stimulating microbial metabolism rather than altering microbial community profiles.
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http://dx.doi.org/10.1016/j.biortech.2021.125592DOI Listing
October 2021

Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy.

Biomaterials 2021 09 12;276:121018. Epub 2021 Jul 12.

Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. Electronic address:

Indoleamine 2,3-dioxygenase (IDO) as a principle enzyme in tryptophan (Trp) catabolism, modulates immune responses and promotes cancer progression. In recent decades, the newly emerging IDO inhibitors are regarded as the breakthrough for cancer immunotherapy. Intensified efforts have been increasingly made to, on the one hand, optimize the IDO inhibitors-based combination therapy in clinical trials; on the other hand, develop IDO inhibitors nanomedicines for tumor-targeted delivery in preclinical studies. This review will discuss the types of IDO inhibitors and the relevant clinical trials, especially those of the feasible combined therapeutic modalities. Moreover, it would be the first time to overview the cutting-edge nanomedicines that combine IDO inhibitors with other therapeutic modalities (e.g., chemotherapy, radiotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and immune checkpoint blockade) to effectively improve the effect of cancer therapy. Lastly, the prospects of IDO inhibitors in terms of clinical application and potential breakthroughs will be briefly discussed.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121018DOI Listing
September 2021

Dynamic nanoassembly-based drug delivery system (DNDDS): Learning from nature.

Adv Drug Deliv Rev 2021 08 15;175:113830. Epub 2021 Jun 15.

Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Dynamic nanoassembly-based drug delivery system (DNDDS) has evolved from being a mere curiosity to emerging as a promising strategy for high-performance diagnosis and/or therapy of various diseases. However, dynamic nano-bio interaction between DNDDS and biological systems remains poorly understood, which can be critical for precise spatiotemporal and functional control of DNDDS in vivo. To deepen the understanding for fine control over DNDDS, we aim to explore natural systems as the root of inspiration for researchers from various fields. This review highlights ingenious designs, nano-bio interactions, and controllable functionalities of state-of-the-art DNDDS under endogenous or exogenous stimuli, by learning from nature at the molecular, subcellular, and cellular levels. Furthermore, the assembly strategies and response mechanisms of tailor-made DNDDS based on the characteristics of various diseased microenvironments are intensively discussed. Finally, the current challenges and future perspectives of DNDDS are briefly commented.
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http://dx.doi.org/10.1016/j.addr.2021.113830DOI Listing
August 2021

A Combination Model of Radiomics Features and Clinical Biomarkers as a Nomogram to Differentiate Nonadvanced From Advanced Liver Fibrosis: A Retrospective Study.

Acad Radiol 2021 May 19. Epub 2021 May 19.

Department of Radiology, Sir Run Run Shaw hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou City, Zhejiang 310016, China. Electronic address:

Rationale And Objectives: To develop and validate a combination model of radiomics features and clinical biomarkers to differentiate nonadvanced from advanced liver fibrosis.

Materials And Methods: One hundred and eight consecutive patients with pathologically diagnosed liver fibrosis were randomly placed in a training or a test cohort at a ratio of 2:1. For each patient, 1674 radiomics features extracted from portal venous phase CT images were reduced by using minimum redundancy and maximum relevant. The optimal features identified were incorporated into the radiomics model. Eight clinical markers were evaluated. Integrated with clinical independent risk factors, a combination model was built. A nomogram was also established from the model. The performance of the models was assessed. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomogram.

Results: The radiomics model established using five features achieved a promising level of discrimination between nonadvanced and advanced liver fibrosis. The combination model incorporated the radiomics signature with two clinical biomarkers and showed good calibration and discrimination. The training and testing cohort results of the radiomics model were area under curve values 0.864 and 0.772, accuracy 77.8% and 77.8%, sensitivity 86.7% and 73.1%, and specificity 71.4% and 90.0%, respectively. For the combination model, the training and testing cohort results were area under curve values 0.915 and 0.897, accuracy 83.3% and 86.1%, sensitivity 86% and 80.6%, and specificity 82.6% and 92.3%, respectively. The decision curve indicated the nomogram has potential in clinical application.

Conclusion: This combination model provides a promising approach for differentiating non-advanced from advanced liver fibrosis.
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http://dx.doi.org/10.1016/j.acra.2020.08.029DOI Listing
May 2021

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment.

Transl Psychiatry 2021 05 20;11(1):303. Epub 2021 May 20.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, China.

Depression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.
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http://dx.doi.org/10.1038/s41398-021-01428-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138009PMC
May 2021

Radiomic features of plaques derived from coronary CT angiography to identify hemodynamically significant coronary stenosis, using invasive FFR as the reference standard.

Eur J Radiol 2021 Jul 9;140:109769. Epub 2021 May 9.

Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, 310010, China. Electronic address:

Objective: This study aimed to investigate the diagnostic performance of radiomics features derived from coronary computed tomography angiography (CCTA) in the identification of ischemic coronary stenosis plaque using invasive fractional flow reserve (FFR) as the reference standard.

Materials And Methods: 174 plaques of 149 patients (age: 62.21 ± 8.47 years, 96 males) with at least one lesion stenosis degree between 30 % and 90 % were retrospectively included. Stenosis degree and plaque characteristics were recorded, and a conventional multivariate logistic model was established. Over 1000 radiomics features of the plaque were derived from CCTA images. The plaques were randomly divided into training set (n = 139) and validation set (n = 35). A random forest model was built. The area under the curve (AUC) of the models was compared.

Results: Fifty-eight radiomics features were correlated with functionally significant stenosis (p <  0.05), wherein 56 features had an AUC of >0.6. NCP volume, NRS, remodeling index, and spotty calcification were included in the conventional model. Ultimately, 14 features were integrated to build the radiomics model. The AUC showed an improvement: 0.71 vs 0.82 for the training set and 0.70 vs 0.77 for the validation set (conventional model and radiomics model, respectively); however, it was not statistically significant (p =  0.58).

Conclusion: The radiomics analysis of plaques showed improvement compared with conventional plaques assessment in identifying hemodynamically significant coronary stenosis. The statistical advancement of machine learning for plaques to predict hemodynamic stenosis with a noninvasive approach still needs further studies on a large-scale dataset.
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http://dx.doi.org/10.1016/j.ejrad.2021.109769DOI Listing
July 2021

Dynamic changes occur in the DNA gut virome of female cynomolgus macaques during aging.

Microbiologyopen 2021 03;10(2):e1186

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Aging is a critical factor affecting physical health and disease in mammals. Emerging evidence indicates that aging may affect the gut bacteriome in cynomolgus macaques, but little is known about whether or how the gut virome changes with age. Here, we compared the DNA gut viral composition of 16 female cynomolgus monkeys (Macaca fascicularis) at three life stages (young, adult, and old) using the shotgun metagenome sequencing method. We found that the DNA gut virome from these monkeys differed substantially among the three groups. The gut viruses were dominated by bacteriophages, the most abundant of which was the Caudovirales order (i.e., Siphoviridae, Myoviridae, and Podoviridae families). Additionally, the co-occurrence analysis revealed that the age-related bacteriophages were correlated in an extensive and complex manner with the main intestinal bacteria (i.e., Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla). Furthermore, the age-related DNA gut viral functions were enriched for genetic information processing, nucleotide, and folate metabolism. Our gut virome analysis provides new insight into how aging influences the gut virome of non-human primates.
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http://dx.doi.org/10.1002/mbo3.1186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087919PMC
March 2021

Tailor-Made Nanomaterials for Diagnosis and Therapy of Pancreatic Ductal Adenocarcinoma.

Adv Sci (Weinh) 2021 04 12;8(7):2002545. Epub 2021 Feb 12.

Institute of Pharmaceutics Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Hangzhou Institute of Innovative Medicine College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide due to its aggressiveness and the challenge to early diagnosis and treatment. In recent decades, nanomaterials have received increasing attention for diagnosis and therapy of PDAC. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the crucial nano-bio interactions in the heterogeneous microenvironment of PDAC remain poorly understood. As a result, the majority of potent nanomedicines show limited performance in ameliorating PDAC in clinical translation. Therefore, exploiting the unique nature of the PDAC by detecting potential biomarkers together with a deep understanding of nano-bio interactions that occur in the tumor microenvironment is pivotal to the design of PDAC-tailored effective nanomedicine. This review will introduce tailor-made nanomaterials-enabled laboratory tests and advanced noninvasive imaging technologies for early and accurate diagnosis of PDAC. Moreover, the fabrication of a myriad of tailor-made nanomaterials for various PDAC therapeutic modalities will be reviewed. Furthermore, much preferred theranostic multifunctional nanomaterials for imaging-guided therapies of PDAC will be elaborated. Lastly, the prospects of these nanomaterials in terms of clinical translation and potential breakthroughs will be briefly discussed.
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http://dx.doi.org/10.1002/advs.202002545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025024PMC
April 2021

Acute necrotising pancreatitis: measurements of necrosis volume and mean CT attenuation help early prediction of organ failure and need for intervention.

Eur Radiol 2021 Mar 23. Epub 2021 Mar 23.

Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Objectives: This study explored the early predictive value of volume and mean CT density of necrosis for adverse outcomes in patients with acute necrotising pancreatitis (ANP).

Methods: A total of 155 patients with ANP who underwent CECT within 7 days of symptom onset were included. The necrosis volume, mean CT density, and modified CT severity index (mCTSI) were calculated. C-reactive protein (CRP) and blood urea nitrogen (BUN) levels both 48 h after symptom onset were reviewed. Adverse outcomes were recorded. The predictive value of each indicator was assessed using ROC curve analysis.

Results: There were significant associations between necrosis volume and mean CT density and organ failure (OF), persistent OF (POF), and need for intervention (p < 0.001 for all). For predicting OF, the area under the curve (AUC) was significantly higher for necrosis volume than for mCTSI and BUN (AUC: 0.84 vs 0.67, p = 0.0011; 0.84 vs 0.71, p = 0.0193, respectively). For predicting POF and need for intervention, the AUCs for necrosis volume were significantly higher than those for mCTSI (AUC: 0.79 vs 0.66, p = 0.0045; 0.77 vs 0.61, p = 0.0019, respectively), but did not significantly differ from those for CRP and BUN. For predicting OF, a significantly better predictive value was achieved with mean CT density than with mCTSI (AUC: 0.79 vs 0.67, p = 0.0163). There were no significant differences in predictive value between mean CT density, CRP, and BUN.

Conclusions: The volume and mean CT density of necrosis based on CECT can provide early prediction of OF, POF, and need for intervention.

Key Points: • Compared to mCTSI, necrosis volume might be used to more accurately diagnose organ failure and persistent organ failure and might be better associated with the need for intervention. • Necrosis volume and mean CT density based on CECT are reliable quantitative predictors for organ failure, persistent organ failure, and intervention in acute pancreatitis.
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http://dx.doi.org/10.1007/s00330-021-07840-xDOI Listing
March 2021

Chemical design of nanozymes for biomedical applications.

Acta Biomater 2021 05 27;126:15-30. Epub 2021 Feb 27.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China; School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

With the advancement of nanochemistry, artificial nanozymes with high catalytic stability, low manufacturing and storage cost, and greater design flexibility over natural enzymes, have emerged as a next-generation nanomedicine. The catalytic activity and selectivity of nanozymes can be readily controlled and optimized by the rational chemical design of nanomaterials. This review summarizes the various chemical approaches to regulate the catalytic activity and selectivity of nanozymes for biomedical applications. We focus on the in-depth correlation between the physicochemical characteristics and catalytic activities of nanozymes from several aspects, including regulating chemical composition, controlling morphology, altering the size, surface modification and self-assembly. Furthermore, the chemically designed nanozymes for various biomedical applications such as biosensing, infectious disease therapy, cancer therapy, neurodegenerative disease therapy and injury therapy, are briefly summarized. Finally, the current challenges and future perspectives of nanozymes are discussed from a chemistry point of view. STATEMENT OF SIGNIFICANCE: As a kind of nanomaterials that performs enzyme-like properties, nanozymes perform high catalytic stability, low manufacturing and storage cost, attracting the attention of researchers from various fields. Notably, chemically designed nanozymes with robust catalytic activity, tunable specificity and multi-functionalities are promising for biomedical applications. It's crucial to define the correlation between the physicochemical characteristics and catalytic activities of nanozymes. To help readers understand this rapidly expanding field, in this review, we summarize various chemical approaches that regulate the catalytic activity and selectivity of nanozymes together with the discussion of related mechanisms, followed by the introduction of diverse biomedical applications using these chemically well-designed nanozymes. Hopefully our review will bridge the chemical design and biomedical applications of nanozymes, supporting the extensive research on high-performance nanozymes.
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http://dx.doi.org/10.1016/j.actbio.2021.02.036DOI Listing
May 2021

The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor.

Chem Commun (Camb) 2021 Mar 24;57(24):3006-3009. Epub 2021 Feb 24.

State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P. R. China.

By targeting the unique Cys663 of EZH2, SKLB-0335 displays high paralog-selectivity on EZH2. Biochemical studies show that SKLB-0335 can covalently bind to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibit H3K27Me3. SKLB-0335 could be an effective chemical probe with which to further investigate the specific biological functions of EZH2.
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http://dx.doi.org/10.1039/d0cc04670aDOI Listing
March 2021

Genomic insights into the formation of human populations in East Asia.

Nature 2021 03 22;591(7850):413-419. Epub 2021 Feb 22.

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.
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http://dx.doi.org/10.1038/s41586-021-03336-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993749PMC
March 2021

Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2.

J Med Chem 2021 03 19;64(5):2829-2848. Epub 2021 Feb 19.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.

EZH2 mediates both PRC2-dependent gene silencing via catalyzing H3K27me3 and PRC2-independent transcriptional activation in various cancers. Given its oncogenic role in cancers, EZH2 has constituted a compelling target for anticancer therapy. However, current EZH2 inhibitors only target its methyltransferase activity to downregulate H3K27me3 levels and show limited efficacy because of inadequate suppression of the EZH2 oncogenic activity. Therefore, therapeutic strategies to completely block the oncogenic activity of EZH2 are urgently needed. Herein, we report a series of EZH2-targeted proteolysis targeting chimeras (PROTACs) that induce proteasomal degradation of PRC2 components, including EZH2, EED, SUZ12, and RbAp48. Preliminary assessment identified as the most active PROTAC molecule, which decreased PRC2 subunits and H3K27me2/3 levels in various cancer cells. Furthermore, strongly inhibited transcriptional silencing mediated by EZH2 dependent on PRC2 and transcriptional activation mediated by EZH2 independent of PRC2, showing significant antiproliferative activities against cancer cell lines dependent on the enzymatic and nonenzymatic activities of EZH2.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02234DOI Listing
March 2021

Intranasal delivery of Paclitaxel encapsulated nanoparticles for brain injury due to Glioblastoma.

J Appl Biomater Funct Mater 2020 Jan-Dec;18:2280800020977170

Department of Neurosurgery, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.

Brain injury is a common cause for physical and emotional effects to the large number of populations. Moreover, glioblastoma is the tumor in brain with no possible treatment leading to death. The blood-brain barrier's makes the treatment more difficult by preventing the drugs to reach central nervous system. Paclitaxel (PTX) encapsulated Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), PTX-PLGA-NPs were developed using emulsification method. The PTX-PLGA-NPs were characterized using Malvern Zetasizer and Scanning Electron Microscopy and were evaluated for their cytotoxicity in U87MG cells. PTX-PLGA-NPs were prepared using single emulsion method having size of 154 ± 22.19 nm with zeta potential of -23.7 mV. The PTX-PLGA-NPs were spherical in shape and have dose dependent cytotoxicity on U87MG cells. The PTX was released from the particles with initial burst release followed by sustained release pattern. The biodistribution was studied in mice with glioblastoma model using I radiolabeled PTX-PLGA-NPs and anti-glioblastoma was studied with PTX-PLGA-NPs. The biodistribution studies revealed PTX-PLGA-NPs after intranasal administration resulted in higher in vivo uptake with high anti-glioblastoma efficacy. The results suggest that PTX-PLGA-NPs administered through intranasal route have potential in the treatment of glioblastoma.
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http://dx.doi.org/10.1177/2280800020977170DOI Listing
December 2020

A non-lab nomogram of survival prediction in home hospice care patients with gastrointestinal cancer.

BMC Palliat Care 2020 Dec 7;19(1):185. Epub 2020 Dec 7.

Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, Guangdong, 515041, People's Republic of China.

Background: Patients suffering from gastrointestinal cancer comprise a large group receiving home hospice care in China, however, little is known about the prediction of their survival time. This study aimed to develop a gastrointestinal cancer-specific non-lab nomogram predicting survival time in home-based hospice.

Methods: We retrospectively studied the patients with gastrointestinal cancer from a home-based hospice between 2008 and 2018. General baseline characteristics, disease-related characteristics, and related assessment scale scores were collected from the case records. The data were randomly split into a training set (75%) for developing a predictive nomogram and a testing set (25%) for validation. A non-lab nomogram predicting the 30-day and 60-day survival probability was created using the least absolute shrinkage and selection operator (LASSO) Cox regression. We evaluated the performance of our predictive model by means of the area under receiver operating characteristic curve (AUC) and calibration curve.

Results: A total of 1618 patients were included and divided into two sets: 1214 patients (110 censored) as training dataset and 404 patients (33 censored) as testing dataset. The median survival time for overall included patients was 35 days (IQR, 17-66). The 5 most significant prognostic variables were identified to construct the nomogram among all 28 initial variables, including Karnofsky Performance Status (KPS), abdominal distention, edema, quality of life (QOL), and duration of pain. In training dataset validation, the AUC at 30 days and 60 days were 0.723 (95% CI, 0.694-0.753) and 0.733 (95% CI, 0.702-0.763), respectively. Similarly, the AUC value was 0.724 (0.673-0.774) at 30 days and 0.725 (0.672-0.778) at 60 days in the testing dataset validation. Further, the calibration curves revealed good agreement between the nomogram predictions and actual observations in both the training and testing dataset.

Conclusion: This non-lab nomogram may be a useful clinical tool. It needs prospective multicenter validation as well as testing with Chinese clinicians in charge of hospice patients with gastrointestinal cancer to assess acceptability and usability.
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http://dx.doi.org/10.1186/s12904-020-00690-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722330PMC
December 2020

SPOCK1: a multi-domain proteoglycan at the crossroads of extracellular matrix remodeling and cancer development.

Am J Cancer Res 2020 1;10(10):3127-3137. Epub 2020 Oct 1.

Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, China.

The SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1 (SPOCK1) is a highly conserved, multi-domain proteoglycan that regulates the dynamic equilibrium of extracellular matrix (ECM). Besides, SPOCK1 is one of the key regulatory genes in the tumor ECM dynamic homeostasis process, which activates many molecular signaling pathways (such as EMT process, Wnt/β-catenin, PI3K/Akt, and mTOR/S6K signaling pathways). This activation leads to ECM remodeling and promotes cell proliferation and invasion, but inhibits cell apoptosis. Whereas there is immense information about SPOCK1's roles in different biological settings, there is need for further studies that interrogate this protein as a potential therapeutic target in cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642659PMC
October 2020

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

Ther Adv Med Oncol 2020 22;12:1758835920963925. Epub 2020 Oct 22.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, China.

Aim: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.

Methods: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A.

Results: In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS placebo (median: not reached 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719;  = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm ( < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS placebo (median: 11.5 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588;  < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm ( < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B).

Conclusion: The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population. ClinicalTrials.gov identifier: NCT02763566.
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http://dx.doi.org/10.1177/1758835920963925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586037PMC
October 2020

Optimization of RNA In Situ Hybridization for mRNA Localization Detection in Mature Tissue of Cucumber Seedlings.

Plants (Basel) 2020 Oct 29;9(11). Epub 2020 Oct 29.

Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, China Agricultural University, Beijing 100193, China.

Cucumber ( L.) is one of the main vegetable crops in China. The physiological cultivation mechanism and gene function characteristics of cucumber are of great significance to the construction of modern agriculture. Due to the low genetic transformation rate of cucumber, only in situ hybridization, which does not involve the progress of gene modified transformation, is convenient to study mRNA localization, so it is more suitable for determination on mRNA localization in the mature tissue of cucumber. At present, the existing in situ hybridization technology system is more suitable for cucumber meristem than for the mature tissue of cucumber seedlings. Therefore, we optimized the traditional plant in situ hybridization protocol. Taking a known gene CsNPF7.2 (Nitrate Transporter Families protein) as an example, we then optimized the steps of plant tissue culture, gene probe preparation, plant material sampling and fixation, preparation of cross section, hybridization pretreatment, hybridization incubation, chromogenic reaction, microscopy examination, and treatment after reaction termination in order to obtain a new RNA in situ hybridization technique suitable for identification on mRNA localization in mature tissues of cucumber seedlings. This optimized technique will ensure the yield of probes, the integrity of RNA molecules, and the clarity and integrity of plant tissue structure, which is conducive to the study of gene function and screening of key genes in cucumber.
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http://dx.doi.org/10.3390/plants9111461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692726PMC
October 2020

Nanoscale zerovalent iron, carbon nanotubes and biochar facilitated the phytoremediation of cadmium contaminated sediments by changing cadmium fractions, sediments properties and bacterial community structure.

Ecotoxicol Environ Saf 2021 Jan 26;208:111510. Epub 2020 Oct 26.

College of Resources and Environment, Hunan Agricultural University, Changsha 410128, China; Key Laboratory for Rural Ecosystem Health in the Dongting Lake Area of Hunan Province, Changsha 410128, China.

Environment functional materials have been widely used, but whether their effects on the contaminated environment could facilitate phytoremediation is not yet well understood. In this study, starch stabilized nanoscale zerovalent iron (SN), multiwall carbon nanotubes (MW) and tea waste derived biochar (TB) were used to facilitate the phytoremediation of cadmium (Cd) contaminated sediments by Boehmeria nivea (L.) Gaudich. Results showed that 100 mg/kg SN, 500 mg/kg MW and 500 mg/kg TB facilitated phytoremediation, as evidenced by increasing Cd accumulation and/or promoting plant growth. These concentrations of materials increased the reducible fraction of Cd by 9-10% and decreased the oxidizable proportion of Cd by 48-52%, indicating the improvement of Cd bioavailability through converting the oxidizable Cd into reducible form. The activities of urease, phosphatase and catalase, which related to nutrient utilization and oxidative stress alleviation, increased by 20-24%, 25-26%, and 8-9% in the sediments treated with 500 mg/kg MW and 500 mg/kg TB, respectively. In addition, the 16S rRNA gene sequence results showed that these concentrations of materials changed the bacterial diversity. The abundance of Acidobacteria, Actinobacteria, Nitrospirae and Firmicutes were increased by some of the applied materials, which could promote plant growth, change Cd bioavailability and reduce Cd toxicity. These findings indicated that the applied environment functional materials could facilitate the phytoremediation of Cd contaminated environment by changing Cd fractions, sediments properties and bacterial community structure.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111510DOI Listing
January 2021

A novel CERNNE approach for predicting Parkinson's Disease-associated genes and brain regions based on multimodal imaging genetics data.

Med Image Anal 2021 01 10;67:101830. Epub 2020 Oct 10.

Hunan Provincial Key Laboratory of Intelligent Computing and Language Information Processing, Hunan Normal University, Changsha 410081, China; College of Information Science and Engineering, Hunan Normal University, Changsha 410081, China.

The detection and pathogenic factors analysis of Parkinson's disease (PD) has a practical significance for its diagnosis and treatment. However, the traditional research paradigms are commonly based on single neural imaging data, which is easy to ignore the complementarity between multimodal imaging genetics data. The existing researches also pay little attention to the comprehensive framework of patient detection and pathogenic factors analysis for PD. Based on functional magnetic resonance imaging (fMRI) data and single nucleotide polymorphism (SNP) data, a novel brain disease multimodal data analysis model is proposed in this paper. Firstly, according to the complementarity between the two types of data, the classical correlation analysis method is used to construct the fusion feature of subjects. Secondly, based on the artificial neural network, the fusion feature analysis tool named clustering evolutionary random neural network ensemble (CERNNE) is designed. This method integrates multiple neural networks constructed randomly, and uses clustering evolution strategy to optimize the ensemble learner by adaptive selective integration, selecting the discriminative features for PD analysis and ensuring the generalization performance of the ensemble model. By combining with data fusion scheme, the CERNNE is applied to forming a multi-task analysis framework, recognizing PD patients and predicting PD-associated brain regions and genes. In the multimodal data experiment, the proposed framework shows better classification performance and pathogenic factors predicting ability, which provides a new perspective for the diagnosis of PD.
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http://dx.doi.org/10.1016/j.media.2020.101830DOI Listing
January 2021

Genetic substructure and admixture of Mongolians and Kazakhs inferred from genome-wide array genotyping.

Ann Hum Biol 2020 Dec 23;47(7-8):620-628. Epub 2020 Nov 23.

Department of Anthropology and Ethnology, Institute of Anthropology, National Institute for Data Science in Health and Medicine, and School of Life Sciences, Xiamen University, Xiamen, China.

Background: Mongolian populations are widely distributed geographically, showing abundant ethnic diversity with geographic and tribal differences.

Aim: To infer the genetic substructure, admixture and ancient genetic sources of Mongolians together with Kazakhs.

Subjects And Methods: We genotyped more than 690,000 genome-wide SNPs from 33 Mongolian and Chinese Kazakh individuals and compared these with both ancient and present-day Eurasian populations using Principal Component Analysis (PCA), ADMIXTURE, -IBD, statistics, and .

Results: We found genetic substructures within Mongolians corresponding to Ölöd, Chahar, and Inner Mongolian clusters, which was consistent with tribe classifications. Mongolian and Kazakh groups derived about 6-40% of West Eurasian related ancestry, most likely from Bronze Age Steppe populations. The East Asian related ancestry in Mongolian and Kazakh groups was well represented by the Neolithic DevilsCave related nomadic lineage, comprising 42-64% of studied groups. We also detected 10-51% of Han Chinese related ancestry in Mongolian and Kazakh groups, especially in Inner Mongolians. The average admixture times for Inner Mongolian, Mongolian_Chahar, Mongolian_Ölöd and Chinese Kazakh were about 1381, 626, 635 and 632 years ago, respectively, with Han and French as the sources.

Conclusion: The DevilsCave related ancestry was once widespread westwards covering a wide geographical range from Far East Russia to the Mongolia Plateau. The formation of present-day Mongolic and Turkic-speaking populations has also received genetic influence from agricultural expansion.
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http://dx.doi.org/10.1080/03014460.2020.1837952DOI Listing
December 2020

Improving mycelial morphology and adherent growth as well as metabolism of Monascus yellow pigments using nitrate resources.

Appl Microbiol Biotechnol 2020 Nov 12;104(22):9607-9617. Epub 2020 Oct 12.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, China.

Mycelial adhesion affects cell growth and the production of water-soluble extracellular yellow pigment (EYP) in submerged fermentation with Monascus ruber CGMCC 10910. Two nitrates, NaNO and KNO, were used as nitrogen sources for mitigating mycelial adhesion and improving the production of EYP in this study. The results showed that the adhesion of mycelia in the fermentation broth significantly decreased by adding 5 g/L NaNO, which prevented mycelia from attaching to the inner wall of the Erlenmeyer flask. It was suggested that NaNO reduced the total amount of extracellular polysaccharides, increased extracellular proteins, and decreased the viscosity of the fermentation broth. Scanning electron microscopy (SEM) analysis revealed that the mycelial morphology was shorter and more dispersed and vigorous under NaNO conditions than under the control conditions. The biomass increased by 49.2% and 45.4% with 5 g/L NaNO and 6 g/L KNO treatment, respectively, compared with that of the control, and the maximum production of EYP was 267.1 and 241.8 AU, which increased by 70.0% and 53.9% compared with that of the control, respectively. Simultaneously, the ratios of intracellular yellow pigment to orange pigment increased significantly with 5 g/L of NaNO addition (p < 0.05). Genetic analysis found that the expression levels of the key genes for Monascus pigment biosynthesis were significantly upregulated by NaNO addition (p < 0.05 or p < 0.01). This study provides an effective strategy for the production of water-soluble Monascus yellow pigments.Key Points• Nitrate addition decreased mycelial adhesion and improved cell growth in Monascus pigment fermentation.• The biosynthesis genes of water-soluble extracellular yellow pigment (EYP) were upregulated by nitrate addition.• The mycelial morphology was significantly influenced to enhance EYP biosynthesis with nitrate addition.
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http://dx.doi.org/10.1007/s00253-020-10944-xDOI Listing
November 2020

Genetic polymorphisms in folate-metabolizing genes associated with gastric cancer prognosis in northwest China subjects.

J Cancer 2020 13;11(21):6413-6420. Epub 2020 Sep 13.

Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, 710038, China.

Influence of folate metabolism has long been studied in cancer and copies evidences have suggested that the key genes involved were correlated with GC risk and prognosis. However, their genetically association and contribution for GC prognosis are still elusive. To evaluate the effect of folate metabolism related genes polymorphisms on the prognosis of gastric cancer (GC), the genotype of seven single nucleotide polymorphisms (SNPs) of three genes were selected and genotyped in a cohort of 664 GC patients, including genes of Methylenetetrahydrofolate reductase (), Methionine synthase reductase (), and Methionine synthase (). Kaplan-Meier Curve, long-rank tests and multivariate Cox proportional hazard model were used for prognosis analysis. The results demonstrated that TT or CT/TT genotypes of SNP rs1532268 in gene coding region are significantly associated with a poorer overall survival (OS) when compared with CC genotype (HR=2.340, 95% CI: 1.240-4.414, =0.009; or HR=1.502, 95% CI: 1.083-2.085, =0.015, respectively). Furthermore, comparing to that of the CC genotype, the detrimental effect of rs1532268 TT genotype was also evident in the special subgroups of GC patients, especially in patients with BMI<24 and H. pylori infection. Moreover, significant association between increased relapse and TT genotype of rs1532268 was also observed in patients who are females, BMI<24 and without chemotherapy. In addition, the joint analysis demonstrated that integration of rs1532268 genotypes and BMI, H. pylori infection status, clinical stage and tumor site may significantly improve the predictive abilities for predicting OS of GC patients. In conclusion, it suggested that the rs1532268 polymorphism is significantly associated with clinical outcomes of GC patients, especially in those with lower BMI (BMI<24) or positive H. pylori infection status, which warrants further validation. And the polymorphism of rs1532268 may be a potential prognostic factor for GC patients.
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http://dx.doi.org/10.7150/jca.46978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532508PMC
September 2020

Nigella A ameliorates inflammation and intestinal flora imbalance in DSS induced colitis mice.

AMB Express 2020 Oct 4;10(1):179. Epub 2020 Oct 4.

Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, People's Republic of China.

Nigella A, also named Sieboldianoside A, has been extracted from many kinds of Traditional Chinese Medicine (TCM), such as Nigella glandulifera, Stauntonia chinensis DC., and the leaves of Acanthopanax sieboldianus. Nigella A exhibited potential analgesic, anti-inflammatory, anti-tumor, and antioxidant activities. However, whether Nigella A could treat ulcerative colitis (UC) is still unknown. As saponins always be regarded as the kinds of ingredients that could regulate immunity and intestinal flora. This research aimed to investigate the therapeutic effect of Nigella A on UC and explore its effect on intestinal flora. We noted that Nigella A and Sulfasalazine (SASP) could significantly improve the signs and symptoms, alleviate colonic pathological injury in DSS-induced mice. The changing of many specific bacterial genus such as Lactobacillus, Porphyromonadaceae, Bacteroides and Escherichia might closely related to the recovery of intestinal inflammatory response. This study initially confirmed the therapeutic effect of Nigella A and SASP on DSS-induced colitis by improving the diversity of intestinal microbial composition. Nigella A has the potential to be developed for the treatment of UC and other disorders related to the imbalance of intestinal flora.
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http://dx.doi.org/10.1186/s13568-020-01114-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533278PMC
October 2020

[Inflammatory mechanism of hippocampal tissue injury induced by PM in nasal drip in mice].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 May;36(3):240-244

School of Public Health and Management, Binzhou Medical College, Yantai 264000.

To investigate the inflammatory mechanism of nasal instillation of fine particulate matter (PM)on hippocampal tissue injury in mice. Thirty C57BL/6J mice were randomly divided into 3 groups(n=10):control group, low-dose group, high-dose group. The nasal instillation doses of PM in the low-dose group and the high-dose group were 1.5 mg/kg BW and 7.5 mg/kg BW, respectively, and the control group was given saline with an equal volume. Saline was sprayed once every other time for 12 times. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by ELISA method. HE staining and electron microscopy were used to observe the pathological changes and ultrastructure of lung tissue and hippocampus. The inflammatory cytokine levels in hippocampus were detected by antibody chip technique. There was no significant effect of PM nasal instillation on serum TNF-α, IL-1β and IL-6 levels (P>0.05), and there was no obvious pathological changes in lung tissue structure. In hippocampus, low-dose and high-dose PM exposure could lead to disordered neuronal arrangement in the hippocampal CA3 region, and there were neurological changes around the neuron cells and ultrastructural changes such as edema around small blood vessels. Compared with the control group, the levels of inflammatory cytokines such as CX3CL1, CSF2 and TECK in the low-dose group were increased significantly (P <0.05), while sTNFR1 was decreased significantly (P<0.05); the inflammatory factors CX3CL1, CSF2, and TCA-3 were significantly increased in the high-dose group (P<0.05), while leptin, MIG, and FASLG were significantly decreased (P<0.05). Nasal instillation of PM can induce tissue damage in the hippocampus of mice, and its mechanism of action may be the olfactory brain pathway. The increasing of TNF-α and IL-6 and the decreasing of sTNFR1 and FASLG may be involved in inflammatory mechanisms.
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http://dx.doi.org/10.12047/j.cjap.5916.2020.053DOI Listing
May 2020
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