Publications by authors named "Qing Wei"

340 Publications

DYF-4 regulates patched-related/DAF-6-mediated sensory compartment formation in C. elegans.

PLoS Genet 2021 Jun 11;17(6):e1009618. Epub 2021 Jun 11.

Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China.

Coordination of neurite extension with surrounding glia development is critical for neuronal function, but the underlying molecular mechanisms remain poorly understood. Through a genome-wide mutagenesis screen in C. elegans, we identified dyf-4 and daf-6 as two mutants sharing similar defects in dendrite extension. DAF-6 encodes a glia-specific patched-related membrane protein that plays vital roles in glial morphogenesis. We cloned dyf-4 and found that DYF-4 encodes a glia-secreted protein. Further investigations revealed that DYF-4 interacts with DAF-6 and functions in a same pathway as DAF-6 to regulate sensory compartment formation. Furthermore, we demonstrated that reported glial suppressors of daf-6 could also restore dendrite elongation and ciliogenesis in both dyf-4 and daf-6 mutants. Collectively, our data reveal that DYF-4 is a regulator for DAF-6 which promotes the proper formation of the glial channel and indirectly affects neurite extension and ciliogenesis.
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http://dx.doi.org/10.1371/journal.pgen.1009618DOI Listing
June 2021

Taurine Attenuates the Hypotaurine-Induced Progression of CRC ERK/RSK Signaling.

Front Cell Dev Biol 2021 15;9:631163. Epub 2021 Apr 15.

Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Colorectal cancer (CRC) is one of the most common malignant tumors, and previous metabolomics work has demonstrated great promise in identifying specific small molecules of tumor phenotype. In the present study, we analyzed the metabolites of resected tissues through gas chromatography-mass spectrometry (GC-MS), and found that the concentration of taurine in CRC tissues diminished whereas the concentration of hypotaurine increased. The results demonstrated that taurine significantly suppressed cellular proliferation, metastasis, and colony formation whereas it induced apoptosis in CRC cells. Furthermore, taurine regulated the expression levels of epithelial mesenchymal transition (EMT)-associated genes in a dose-dependent manner. Taurine also alleviated hypotaurine-induced CRC progression, which was linked to the inhibition of the ERK/RSK-signaling pathway and diminution in intracellular hypotaurine. Taurine additionally attenuated hypotaurine-induced tumor growth and metastasis Patients with CRC exhibited lower levels of serum taurine, suggesting that taurine might be a promising biomarker reflecting a poor prognosis in CRC. Collectively, our results demonstrated that taurine-attenuated, hypotaurine-induced CRC progression provides a potential target for CRC therapy.
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http://dx.doi.org/10.3389/fcell.2021.631163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083965PMC
April 2021

Glioma grading, molecular feature classification, and microstructural characterization using MR diffusional variance decomposition (DIVIDE) imaging.

Eur Radiol 2021 Apr 29. Epub 2021 Apr 29.

Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.

Objective: To evaluate the potential of diffusional variance decomposition (DIVIDE) for grading, molecular feature classification, and microstructural characterization of gliomas.

Materials And Methods: Participants with suspected gliomas underwent DIVIDE imaging, yielding parameter maps of fractional anisotropy (FA), mean diffusivity (MD), anisotropic mean kurtosis (MK), isotropic mean kurtosis (MK), total mean kurtosis (MK), MK/MK, and microscopic fractional anisotropy (μFA). Tumor type and grade, isocitrate dehydrogenase (IDH) 1/2 mutant status, and the Ki-67 labeling index (Ki-67 LI) were determined after surgery. Statistical analysis included 33 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG). Tumor diffusion metrics were compared between HGG and LGG, among grades, and between wild and mutated IDH types using appropriate tests according to normality assessment results. Receiver operating characteristic and Spearman correlation analysis were also used for statistical evaluations.

Results: FA, MD, MK, MK, MK, μFA, and MK/MK differed between HGG and LGG (FA: p = 0.047; MD: p = 0.037, others p < 0.001), and among glioma grade II, III, and IV (FA: p = 0.048; MD: p = 0.038, others p < 0.001). All diffusion metrics differed between wild-type and mutated IDH tumors (MK: p = 0.003; others: p < 0.001). The metrics that best discriminated between HGG and LGGs and between wild-type and mutated IDH tumors were MK and FA respectively (area under the curve 0.866 and 0.881). All diffusion metrics except FA showed significant correlation with Ki-67 LI, and MK had the highest correlation coefficient (r = 0.618).

Conclusion: DIVIDE is a promising technique for glioma characterization and diagnosis.

Key Points: • DIVIDE metrics MK is related to cell density heterogeneity while MK and μFA are related to cell eccentricity. • DIVIDE metrics can effectively differentiate LGG from HGG and IDH mutation from wild-type tumor, and showed significant correlation with the Ki-67 labeling index. • MK was larger than MK which indicates predominant cell density heterogeneity in gliomas. • MK and MK increased with grade or degree of malignancy, however with a relatively larger increase in the cell eccentricity metric MK in relation to the cell density heterogeneity metric MK.
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http://dx.doi.org/10.1007/s00330-021-07959-xDOI Listing
April 2021

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Regulate Macrophage Polarization to Attenuate Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage in Mice.

Int J Stem Cells 2021 Apr 30. Epub 2021 Apr 30.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China.

Background And Objectives: To investigate the effect and the underlying mechanism of exosomes secreted by human umbilical cord mesenchymal stem cells (hUCMSCs) on diffuse alveolar hemorrhage (DAH) in murine lupus.

Methods And Results: Exosomes were extracted from cultured hUCMSCs by ultracentrifugation. The expressions of exosome markers (Alix, CD63 and TSG101) were measured for identification of hUCMSC-derived exosomes (hUCMSC-exosomes). The alveolar hemorrhage of DAH mice was revealed by H&E staining. The primary alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) of DAH mice. The expressions of M1 macrophage markers (iNOS, IL-6, TNF- and IL-1) and M2 macrophage markers (Arg1, IL-10, TGF- and chi3l3) were detected. Flow cytometry measured the ratio of M1/M2 macrophages. ELISA measured the secretion of pro-inflammatory cytokines (IL-6 and TNF-) and anti-inflammatory cytokines (IL-10 and TGF-). DAH mice had hemorrhage and small-vessel vasculitis in the lung, with neutrophil and monocyte infiltration observed around the capillary and small artery. Furthermore, increases of IL-6 and TNF-, and decreases of IL-10 and TGF- were detected in the BALF of DAH mice. M1 makers were overexpressed in alveolar macrophages of DAH mice while M2 makers were lowly expressed. DAH mice had a higher proportion of M1 macrophages than M2 macrophages. After hUCMSC-exosome or methylprednisolone treatment in DAH mice, the alveolar injuries and inflammatory responses were attenuated, and the proportion of M2 macrophages was increased.

Conclusions: hUCMSC-exosomes attenuate DAH-induced inflammatory responses and alveolar hemorrhage by regulating macrophage polarization.
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http://dx.doi.org/10.15283/ijsc20156DOI Listing
April 2021

Changes in the expression levels of elastic fibres in yak lungs at different growth stages.

BMC Dev Biol 2021 04 20;21(1). Epub 2021 Apr 20.

College of Eco-Environmental Engineering, Qinghai University, 251 Ningda Road, Xining, 810016, Qinghai, China.

Background: Yaks have a strong adaptability to the plateau environment, which can be attributed to the effective oxygen utilization rate of their lung tissue. Elastic fibre confers an important adaptive structure to the alveolar tissues in yaks. However, little research has been focused on the structural development of lung tissues and the expression levels of elastic fibres in yaks after birth. Therefore, this study aimed to investigate the morphological changes of elastic fibers and expression profiles of fibre-formation genes in yak lungs at different growth stages and the relationship between these changes and plateau adaptation.

Results: Histological staining was employed to observe the morphological changes in the lung tissue structure of yaks at four different ages: 1 day old, 30 days old, 180 days old and adult. There was no significant difference in the area of a single alveolus between the 1-day-old and 30-day-old groups (P-value > 0.05). However, the single alveolar area was gradually increased with an increase in age (P-value < 0.05). Elastic fibre staining revealed that the amount of elastic fibres in alveolar tissue was increased significantly from the ages of 30 days to 180 days (P-value < 0.05) and stabilized during the adult stage. Transcriptome analysis indicated that the highest levels of differentially expressed genes were found between 30 days of age and 180 days of age. KEGG analysis showed that PI3K-Akt signalling pathway and MAPK pathway, which are involved in fibre formation, accounted for the largest proportion of differentially expressed genes between 30 days of age and 180 days of age. The expression levels of 36 genes related to elastic fibre formation and collagen fibre formation were also analysed, and most of these genes were highly expressed in 30-day-old and 180-day-old yaks.

Conclusions: The content of elastic fibres in the alveolar tissue of yaks increases significantly after birth, but this change occurs only from 30 days of age to 180 days of age. Our study indicates that elastic fibres can improve the efficiency of oxygen utilization in yaks under harsh environmental conditions.
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http://dx.doi.org/10.1186/s12861-021-00240-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056501PMC
April 2021

Systemic Inflammatory Markers of Resectable Colorectal Cancer Patients with Different Mismatch Repair Gene Status.

Cancer Manag Res 2021 30;13:2925-2935. Epub 2021 Mar 30.

Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang Province, 310022, People's Republic of China.

Background: We aimed to assess the differences in gene expression and systemic inflammatory markers in colorectal cancer (CRC) patients with different mismatch repair (MMR) statuses.

Methods: Bioinformatics analysis was used to identify the different expression genes in patients with CRC at different MMR statuses. A total of 208 patients with resectable colorectal cancer, including 104 deficient mismatch repair (dMMR) patients and 104 matched proficient mismatch repair (pMMR) patients, were retrospectively analyzed.

Results: Bioinformatics analysis showed that chemokine-mediated signaling pathway and inflammatory responses were the main differences in gene expression between dMMR and pMMR CRC patients. In all 208 patients with CRC, those with dMMR frequently had it located on the right side, with more mucinous adenocarcinoma and grade 3 tumors. Patients with dMMR had an earlier American Joint Committee on Cancer (AJCC) stage than pMMR patients. Meanwhile, lymph nodes (LNs) metastasis was more frequently negative in dMMR patients than pMMR patients. Interestingly, patients with CRC with dMMR had more regional lymph nodes removed during surgery, although with less metastatic cancer. Patients with resectable CRC with dMMR were more likely to have higher levels of neutrophil, monocyte, platelet, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and C-reactive protein (CRP). In patients with dMMR, those with higher levels of PLR, MLR, CAR, and co-effect present had shorter overall survival (OS) significantly. It was noteworthy that the prognosis of high levels of systemic inflammatory markers did not predict prolonged OS in patients with pMMR CRC.

Conclusion: dMMR CRC has presented a comprehensively distinct systemic inflammatory microenvironment. The systemic inflammatory response can predict oncological outcomes in patients with CRC with dMMR.
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http://dx.doi.org/10.2147/CMAR.S298885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019618PMC
March 2021

Dose-response relationship between serum 25-hydroxyvitamin D and the risk of metabolic syndrome.

Clin Nutr 2021 Apr 4;40(4):1530-1536. Epub 2021 Mar 4.

Health Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Background & Aims: There are conflicting results for the association of 25-hydroxyvitamin D [25(OH)D] with metabolic syndrome (MetS). The aim of this study was to investigate the relationship between serum 25(OH)D concentration and MetS and its components in a Chinese adult population.

Methods: A cross-sectional study of 25,691 men and 22,146 women from China was performed in 2017. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel Ш. Logistic and restricted cubic spline regression analyses were used to assess the association between 25(OH)D and MetS.

Results: Of the 43,837 participants aged 18-96 years, the prevalence of MetS was 21.0%. The adjusted odds ratios (ORs) for MetS decreased gradually with increasing 25(OH)D concentrations (P for trend < 0.001). Compared with the lowest 25(OH)D quartile, the adjusted ORs (95% CIs) for MetS from second to the highest quartile were 0.95 (0.88-1.02), 0.82 (0.76-0.88), and 0.70 (0.65-0.75), respectively. We observed a linear dose-response relationship between 25(OH)D concentrations and MetS risk (P for nonlinear trend = 0.35); the risk of MetS decreased by 20% (OR = 0.80, 95%CI: 0.77-0.82) for each 10 ng/ml increment in 25(OH)D concentration. The inverse association was more evident in men and participants with eGFR <60 ml/min/1.73 m or AST ≥40 U/L (all P for interaction < 0.05). Moreover, significant inverse relationships were observed between 25(OH)D and elevated triglycerides, reduced high-density lipoprotein cholesterol and elevated blood pressure.

Conclusions: These findings suggested that higher 25(OH)D concentrations were independently associated with a dose-response decreased risk of MetS among Chinese adults.
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http://dx.doi.org/10.1016/j.clnu.2021.02.031DOI Listing
April 2021

Effect of 'hand and foot acupuncture with twelve needles' on hemiplegia patients with 'qi deficiency and blood stasis' syndrome in the convalescent stage of Ischaemic stroke: study protocol for a randomised controlled trial.

Trials 2021 Mar 18;22(1):215. Epub 2021 Mar 18.

Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing, 101300, China.

Background: Hemiplegia is a common sequela after stroke, and acupuncture is one of the most common physical therapies used to treat hemiplegia during the recovery stage after ischaemic stroke. 'Hand and foot acupuncture with twelve needles' is an acupuncture treatment performed after stroke. The principal objective of this study is to assess the efficacy and safety of 'hand and foot acupuncture with twelve needles' for hemiplegia in the convalescent stage of ischaemic stroke.

Methods: This is the protocol for a randomised, controlled clinical trial with two groups: a 'hand and foot acupuncture with twelve needles' group and a routine acupuncture group. A total of 208 participants will be randomly assigned to two different groups in a 1:1 ratio and will undergo conventional rehabilitation. Limb function will be evaluated by the simplified Fugl-Meyer assessment scale, Barthel Index, modified Ashworth scale and National Institute of Health stroke scale. The participants will be evaluated at baseline (on the day of enrolment) and followed up at 2 weeks, 1 month, 2 months and 3 months after enrolment.

Discussion: The results of this study will provide evidence on the effectiveness of 'hand and foot acupuncture with twelve needles' in the treatment of limb dysfunction that can be used for future evaluations.

Trial Registration: Chictr.org.cn ChiCTR1900021774 . Registered on 8 March 2019.
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http://dx.doi.org/10.1186/s13063-021-05128-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977321PMC
March 2021

Immunological impact of chemotherapy on the tumor microenvironment in gastric cancer.

J Surg Oncol 2021 May 8;123(8):1708-1715. Epub 2021 Mar 8.

Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, PR China.

Objective: This study aimed to investigate alterations in pre- and post-neoadjuvant chemotherapy (NACT) tumor-infiltrating immune cells and subsequent evaluation of the predictive and prognostic value of these changes in gastric cancer (GC).

Methods: Fifty patients with GC underwent three cycles of S-1 and oxaliplatin (SOX regimen)-NACT. Paired samples from tumor lesions before and after NACT were available for all patients participating in the study. Immunohistochemistry was performed for T cell subsets (CD3 and CD8 ) and macrophages (CD68 and CD163 ).

Results: After NACT, the average expression levels of CD3, CD8, CD68, and CD163 were significantly increased (p < .001). However, neither expression levels pre- nor post-chemotherapy correlated with treatment response. Multivariate Cox regression analysis demonstrated that upregulation of CD8/CD3 levels (hazard ratio [HR] = 0.117; 95% confidence interval [CI] = 0.031-0.446; p = 0.002) and CD163 levels after chemotherapy (HR = 2.258; 95% CI = 1.047-4.867; p = 0.038) were independent prognostic factors of overall survival.

Conclusion: Chemotherapy in GC is useful to induce CD3 and CD8 T lymphocytes as well as CD68 and CD163 macrophages in the tumor microenvironment in combination with its direct cytotoxic effects. These results indicate that chemotherapy may play a role in tumor immune microenvironment remodeling.
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http://dx.doi.org/10.1002/jso.26449DOI Listing
May 2021

Conserved role of ATP synthase in mammalian cilia.

Exp Cell Res 2021 Apr 24;401(1):112520. Epub 2021 Feb 24.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. Electronic address:

We previously found that ATP synthases localize to male-specific sensory cilia and control the ciliary response by regulating polycystin signalling in Caenorhabditis elegans. Herein, we discovered that the ciliary localization of ATP synthase is evolutionarily conserved in mammals. We showed that the ATP synthase subunit F1β is colocalized with the cilia marker acetylated α-tubulin in both mammalian renal epithelial cells (MDCK) and normal mouse cholangiocytes (NMCs). Treatment with ATP synthase inhibitor oligomycin impaired ciliogenesis in MDCK cells, and F1β was co-immunoprecipitated with PKD2 in mammalian cells. Our study provides evidence for the evolutionarily conserved localization of ATP synthase in cilia from worm to mammals. Defects in ATP synthase can lead to ciliary dysfunction, which may be a potential mechanism of polycystic kidney disease.
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http://dx.doi.org/10.1016/j.yexcr.2021.112520DOI Listing
April 2021

Deep Reinforcement Learning With Quantum-Inspired Experience Replay.

IEEE Trans Cybern 2021 Feb 18;PP. Epub 2021 Feb 18.

In this article, a novel training paradigm inspired by quantum computation is proposed for deep reinforcement learning (DRL) with experience replay. In contrast to the traditional experience replay mechanism in DRL, the proposed DRL with quantum-inspired experience replay (DRL-QER) adaptively chooses experiences from the replay buffer according to the complexity and the replayed times of each experience (also called transition), to achieve a balance between exploration and exploitation. In DRL-QER, transitions are first formulated in quantum representations and then the preparation operation and depreciation operation are performed on the transitions. In this process, the preparation operation reflects the relationship between the temporal-difference errors (TD-errors) and the importance of the experiences, while the depreciation operation is taken into account to ensure the diversity of the transitions. The experimental results on Atari 2600 games show that DRL-QER outperforms state-of-the-art algorithms, such as DRL-PER and DCRL on most of these games with improved training efficiency and is also applicable to such memory-based DRL approaches as double network and dueling network.
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http://dx.doi.org/10.1109/TCYB.2021.3053414DOI Listing
February 2021

MicroRNA-124-3p affects myogenic differentiation of adipose-derived stem cells by targeting Caveolin-1 during pelvic floor dysfunction in Sprague Dawley rats.

Ann Transl Med 2021 Jan;9(2):161

Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The aim of this study was to investigate using myogenic differentiation of adipose stem cells for the treatment of female pelvic floor dysfunction (PFD) and aimed to further study the influences of microRNA-124-3p (miR-124-3p) in the process of myogenic differentiation of adipose-derived stem cells (ADSCs) through targeting Caveolin-1 (Cav1) during PFD in Sprague Dawley (SD) rats.

Methods: The ADSCs were separated from 6-8-week-old female SD rats (n=25) and were cultivated. Then, we observed the cell status and conducted fat and osteogenic experiments. We then constructed an ADSC-green fluorescent protein (GFP) stable transfer strain. Flow cytometry was used to identify the positive rates of CD44, CD90, and CD45 in ADSCs and ADSC-GFP. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were used to mRNA and protein expression levels. Myogenic differentiation of ADSCs was measured with immunofluorescence methods. A dual-luciferase reporter assay was executed to affirm whether Cav1 was a target of miR-124-3p.

Results: The isolated ADSCs cells were in good condition under the microscope. The results of flow cytometry showed that the positive rate of CD44 and CD90 was high, and the positive rate of CD45 was low in ADSCs and ADSC-GFP. Under normal culture conditions, ADSCs-GFP cells can be massively adipated and osteogenic. After 5-Aza induced ADSC-GFP myogenic differentiation, the level of miR-124-3p was significantly increased. We found that MiR-124-3p mimics promoted the myogenic differentiation of ADSCs. Moreover, we discovered that Cav1 was a target gene of miR-124-3p and was negatively regulated by miR-124-3p. The results of leak point pressure (LPP), hematoxylin and eosin (HE), and Masson showed that the collagen fiber content of the PFD group was lower than that of the control group; the collagen fiber content of ADSC-GFP, 5-Aza, or miR-124-3p mimics were increased after intervention. Furthermore, the outcomes qRT-PCR, western blotting, and immunofluorescence suggested that miR-124-3p facilitated the survival ADSC-GFP fat transplantation by regulating many key factors in vivo.

Conclusions: These results proofed that miR-124-3p could accelerate myogenic differentiation of ADSCs by down-regulating Cav1 to improve PFD in SD rats, which will pave the way for therapeutic delivery of miRNA targeting PFD disease.
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http://dx.doi.org/10.21037/atm-20-8212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867888PMC
January 2021

miR-31 Displays Subtype Specificity in Lung Cancer.

Cancer Res 2021 Apr 8;81(8):1942-1953. Epub 2021 Feb 8.

Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.

miRNA rarely possess pan-oncogenic or tumor-suppressive properties. Most miRNAs function under tissue-specific contexts, acting as either tumor suppressors in one tissue, promoting oncogenesis in another, or having no apparent role in the regulation of processes associated with the hallmarks of cancer. What has been less clear is the role of miRNAs within cell types of the same tissue and the ability within each cell type to contribute to oncogenesis. In this study, we characterize the role of one such tissue-specific miRNA, miR-31, recently identified as the most oncogenic miRNA in lung adenocarcinoma, across the histologic spectrum of human lung cancer. Compared with normal lung tissue, miR-31 was overexpressed in patient lung adenocarcinoma, squamous cell carcinoma, and large-cell neuroendocrine carcinoma, but not small-cell carcinoma or carcinoids. miR-31 promoted tumor growth in mice of xenografted human adenocarcinoma and squamous cell carcinoma cell lines, but not in large- or small-cell carcinoma lines. While miR-31 did not promote primary tumor growth of large- and small-cell carcinoma, it did promote spontaneous metastasis. Mechanistically, miR-31 altered distinct cellular signaling programs within each histologic subtype, resulting in distinct phenotypic differences. This is the first report distinguishing diverse functional roles for this miRNA across the spectrum of lung cancers and suggests that miR-31 has broad clinical value in human lung malignancy. SIGNIFICANCE: These findings demonstrate the oncogenic properties of miR-31 in specific subtypes of lung cancer and highlight it as a potential therapeutic target in these subtypes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/8/1942/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137562PMC
April 2021

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens.

Front Genet 2020 11;11:574167. Epub 2021 Jan 11.

College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in chickens have been rarely studied. H3K27ac chromatin immunoprecipitation coupled with high-throughput sequencing and high-throughput RNA sequencing was performed to compare genome-wide H3K27ac profiles and transcriptomes of liver tissue between healthy and FLHS chickens. In total, 1,321 differential H3K27ac regions and 443 differentially expressed genes were identified (| log2Fold change| ≥ 1 and -value ≤ 0.05) between the two groups. Binding motifs for transcription factors involved in immune processes and metabolic homeostasis were enriched among those differential H3K27ac regions. Differential H3K27ac peaks were associated with multiple known FLHS risk genes, involved in lipid and energy metabolism (, , , and ) and the immune system (, , and ). Previous studies and our current results suggested that the high-energy, low-protein (HELP) diet might have an impact on histone modification and chromatin structure, leading to the dysregulation of candidate genes and the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which causes excessive accumulation of fat in the liver tissue and induces the development of FLHS. These findings highlight that epigenetic modifications contribute to the regulation of gene expression and play a central regulatory role in FLHS. The PPAR signaling pathway and other genes implicated in FLHS are of great importance for the development of novel and specific therapies for FLHS-susceptible commercial laying hens.
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http://dx.doi.org/10.3389/fgene.2020.574167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831272PMC
January 2021

Efficacy and safety of domestic and imported gefitinib in patients with advanced non-small cell lung cancer.

Ann Palliat Med 2021 Jan 11;10(1):10-15. Epub 2021 Jan 11.

Department of Pharmacy, Tong Ren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China. Email:

Background: Gefitinib is a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It was approved by the U.S. Food and Drug Administration (FDA) for clinical use in 2003. However, gefitinib has only come to China in recent years. Previous studies have not compared the efficacy and safety of domestic and imported gefitinib. Therefore, we conducted this study.

Methods: This study included 227 patients with advanced non-small cell lung cancer (NSCLC) who received gefitinib treatment in four medical institutions: The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Fudan University Shanghai Cancer Center, Shandong Provincial Institute of Cancer Prevention and Jiangsu Cancer Hospital, from January 2017 to July 2018. The patients were divided into a Yiruike group (55 patients treated with domestic gefitinib, Yiruike) and an Iressa group (172 patients treated with imported gefitinib, Iressa). Because gefitinib resistance usually occurs within 8-10 months of gefitinib administration, the patients were followed up for one year to observe their conditions and compare the occurrence of adverse reactions between the two groups.

Results: The two groups had no significant difference in baseline data. The median progression-free survival (PFS) of Yiruike group and that of Iressa group were 10.270±2.036 and 12.970±1.634 months, respectively. The mean PFS of Yiruike group and that of Iressa group were 12.598±1.083 and 15.958±0.987 months, respectively. The one-year disease control rate (DCR) of Yiruike group and that of Iressa group were 61.8% and 59.3%, respectively. The differences were all insignificant (P>0.05). The incidence of adverse reactions in these two groups were not significantly different.

Conclusions: Yiruike was slightly superior to Iressa in terms of DCR. However, comparisons of bioequivalence and DCR were not sufficient for evaluating a drug. Other comparisons require long-term follow-up studies with a large sample size.
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http://dx.doi.org/10.21037/apm-20-2140DOI Listing
January 2021

Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.

Allergy Asthma Clin Immunol 2021 Jan 6;17(1). Epub 2021 Jan 6.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.

Background: The pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.

Methods: Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n = 12) group, neutrophilic asthma (NA, n = 10) group and paucigranulocytic asthma (PGA, n = 6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n = 10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA.

Results: The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other.

Conclusions: Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.
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http://dx.doi.org/10.1186/s13223-020-00504-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789788PMC
January 2021

Traditional Chinese Medicine Tanreqing Inhibits Quorum Sensing Systems in .

Front Microbiol 2020 17;11:517462. Epub 2020 Dec 17.

Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.

is an opportunistic pathogen that can infect a wide variety of hosts including humans, plants, and animals. The production of virulence factors is the determinant of the infection paradigm and is under orchestrated regulation via cell-to-cell communication process called quorum sensing (QS). To disable QS circuits and prevent bacterial infections, a large battery of anti-QS agents, particularly from traditional Chinese medicine have been developed. Here, we used as a model microorganism to investigate the effect of traditional Chinese medicine Tanreqing (TRQ) formula on bacterial pathogenicity. Phenotypic analysis showed that TRQ treatment could completely inhibit the production of phenazine pyocyanin and moderately inhibit the production of virulence factors such as rhamnolipids, elastase, and alkaline protease. Further transcriptomic analyses revealed that TRQ treatment could significantly attenuate the expression of QS-regulated genes in and TRQ-treated regulon shared a large overlap with QS regulon. Component contribution to QS inhibition shed light on the indispensable role of all five components in TRQ formula. Further genetic analysis indicated that upstream regulators of QS systems, including two-component systems GacS/GacA and PprA/PprB, were both inhibited by TRQ treatment. Finally, our TRQ formula could efficiently protect from killing by . Altogether, we have proved TRQ formula as an effective and specific agent to attenuate bacterial virulence and combat bacterial infections.
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http://dx.doi.org/10.3389/fmicb.2020.517462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775676PMC
December 2020

Association between iron status and the risk of adverse outcomes in COVID-19.

Clin Nutr 2021 05 9;40(5):3462-3469. Epub 2020 Dec 9.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background & Aims: Iron is an essential trace element to almost all organism, and the delicate balance between host defend system and viral proliferation plays an important role in infective conditions. While the association of the iron metabolism with the prognosis of COVID-19 remains poorly understood. We aimed to estimate the associations of systemic iron metabolism parameters with the severity and risks of adverse outcomes in COVID-19.

Methods: In this retrospective cohort study, we included 158 confirmed COVID-19 patients in Tongji Hospital, Wuhan, China (27 January to 5 April, 2020). Demographic data, comorbidities, laboratory examinations, treatments, and clinical outcomes were all collected. Multivariable Poisson regression was used to estimate the association of iron parameter levels with the severity and risks of adverse outcomes in COVID-19 patients.

Results: We identified 60 (38%) severe cases in 158 COVID-19 patients. The median age was 63 years (interquartile range [IQR]: 54-73) and the median length of hospital stay was 28 days (IQR: 17-40). After adjusting for age, sex, IL-6, and pre-existing comorbidities, all iron parameters were associated with the severity of COVID-19 with adjusted risk ratio of 0.42 [95% CI: 0.22-0.83], 4.38 [95% CI: 1.86-10.33], 0.19 [95% CI: 0.08-0.48], and 0.25 [95% CI: 0.10-0.58] for serum iron, ferritin, transferrin, and total iron-binding capacity, respectively. These iron indices were also related to the risk of ARDS, coagulopathy, acute cardiac injury, acute liver injury, and acute kidney injury in COVID-19 patients and high cytokine concentrations.

Conclusions: Patients with low serum iron status likely suffered from severe condition and multiple-organ injury in COVID-19. The iron metabolism parameters might be risk factors and clinical biomarkers for COVID-19 prognosis.
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http://dx.doi.org/10.1016/j.clnu.2020.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723754PMC
May 2021

Improved Detonation Performance Via Coordination Substitution: Synthesis and Characterization of Two New Green Energetic Coordination Polymers.

ACS Appl Mater Interfaces 2021 Jan 29;13(1):563-569. Epub 2020 Dec 29.

Key Laboratory of Synthetic & Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an 710127, China.

In this work, a new energetic coordination polymer (ECP), [Cu(HBTI)(HO)] () (HBTI = 4,5-bistetrazole-imidazole), was synthesized by a hydrothermal method. Due to the existence of coordination water molecules in , however, its energy density was limited, which led to the insufficient detonation performance. To further improve its detonation performance, [Cu(HBTI)(NO)] () was then obtained by substituting the coordinated water molecule in with nitrate through the coordination substitution reaction under acidic conditions. The structures of two ECPs were respectively characterized using X-ray single-crystal diffraction, and the theoretical density of (2.227 g·cm) was greater than (1.851 g·cm). Thermogravimetric analyses showed that has a one-step rapid weight loss process compared with the two-step slow weight loss process of . The theoretical calculations indicated that the detonation performances of were better than those of . Moreover, the promotion effects of two ECPs on the combustion decomposition of ammonium perchlorate were studied using a differential scanning calorimetry method.
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http://dx.doi.org/10.1021/acsami.0c18271DOI Listing
January 2021

CEP290 is essential for the initiation of ciliary transition zone assembly.

PLoS Biol 2020 12 28;18(12):e3001034. Epub 2020 Dec 28.

Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Cilia play critical roles during embryonic development and adult homeostasis. Dysfunction of cilia leads to various human genetic diseases, including many caused by defects in transition zones (TZs), the "gates" of cilia. The evolutionarily conserved TZ component centrosomal protein 290 (CEP290) is the most frequently mutated human ciliopathy gene, but its roles in ciliogenesis are not completely understood. Here, we report that CEP290 plays an essential role in the initiation of TZ assembly in Drosophila. Mechanistically, the N-terminus of CEP290 directly recruits DAZ interacting zinc finger protein 1 (DZIP1), which then recruits Chibby (CBY) and Rab8 to promote early ciliary membrane formation. Complete deletion of CEP290 blocks ciliogenesis at the initiation stage of TZ assembly, which can be mimicked by DZIP1 deletion mutants. Remarkably, expression of the N-terminus of CEP290 alone restores the TZ localization of DZIP1 and subsequently ameliorates the defects in TZ assembly initiation in cep290 mutants. Our results link CEP290 to DZIP1-CBY/Rab8 module and uncover a previously uncharacterized important function of CEP290 in the coordination of early ciliary membrane formation and TZ assembly.
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http://dx.doi.org/10.1371/journal.pbio.3001034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793253PMC
December 2020

Effect of Hordei Fructus Germinatus on differential gene expression in the prolactin signaling pathway in the mammary gland of lactating rats.

J Ethnopharmacol 2021 Mar 18;268:113589. Epub 2020 Nov 18.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China; College of TCM, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address:

Ethnopharmacological Relevance: In China, Hordei Fructus Germinatus (HFG) is the germinated and dried fruit of Hordeum vulgare L, which is commonly used in clinical Chinese medicine. Traditional Chinese Medicine (TCM) theory holds that HFG can be both medicinal and edible, which means that it is derived from food medicine. Raw HFG and roasted HFG are used to treat hypogalactia, hyperprolactinemia and indigestion. In recent years, the lactogenic and galactophygous effects of HFG have attracted increasing attention. Nevertheless, there is much confusion over the use of raw and processed HFG, and the mechanism of its lactogenic effect seems remains poorly understood.

Aim Of The Study: This study aimed to explore the lactogenic effect of raw HFG and roasted HFG on rats with overloaded lactation and to reveal the underlying molecular mechanism.

Materials And Methods: Raw and processed HFG water decoctions were given to overloaded lactation model rats at a dose of 1.7800 g kg·d, and the control group was given the same volume of water. The lactogenic effect of raw and processed HFG was evaluated by measuring daily lactation, body weight and pup body weight, serum PRL, E2, and GH contents after parturition, and the pathological characteristics of mammary tissue sections. cDNA microarrays can be used to screen diverse gene expression patterns and signaling pathways related to prolactin. The expression of relevant differentially expressed genes was verified by real-time PCR and western blotting.

Results: In vivo experiments demonstrated that the raw HFG water decoction stimulated mammogenesis, accelerated the transformation of the lobular acinar system, resulted in denser mammary epithelial cells and thicker glandular ducts that were full of milk and facilitated the secretion of milk. Moreover, HFG increased PRL, E2, and GH levels, pup body weight, daily lactation and the body weight of lactating rats. Following gene chip identification, KEGG pathway enrichment analysis revealed genes that were highly related to prolactin in the prolactin signaling pathway and JAK-STAT signaling pathway, and the main differentially expressed genes were Jak2 (down), Stat5α (up), cyclin D1 (up), SOCS1 (up), CISH (down) and PRLR (up). Compared with the control group, RT-PCR results indicated that Jak2 and CISH were downregulated and that Stat5α, cyclin D1, SOCS1 and PRLR were upregulated. Western blot assays showed that PRLR, STAT5α and cyclin D1 levels in the mammary glands of the raw HFG water decoction group were significantly increased, which was consistent with the results of cDNA microarray screening.

Conclusion: The present study reveals that raw HFG effectively enhances lactation in rats, possibly by influencing the prolactin/JAK-STAT signaling pathway.
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http://dx.doi.org/10.1016/j.jep.2020.113589DOI Listing
March 2021

Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies.

iScience 2020 Nov 21;23(11):101711. Epub 2020 Oct 21.

Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, Birmingham, AL 35294, USA.

HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion. How each glycan interacts to shape the Env-protein-sugar complex and affects Env function is not well understood. Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization. Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing. Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss. This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
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http://dx.doi.org/10.1016/j.isci.2020.101711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649354PMC
November 2020

Centrosome Protein 78 Is Overexpressed in Muscle-Invasive Bladder Cancer and Is Associated with Tumor Molecular Subtypes and Mutation Signatures.

Med Sci Monit 2020 Oct 29;26:e925197. Epub 2020 Oct 29.

Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).

BACKGROUND Centrosome aberrations have long been linked to tumorigenesis. Centrosome protein 78 (CEP78) is a centrosome component that is required to regulate the cell cycle, but its role in bladder cancer has not been elucidated. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and immunohistochemistry were used to examine the expression of CEP78 in bladder cancer tissues and adjacent non-cancer tissues. RESULTS Analysis of the RNA-Seq data from the TCGA (The Cancer Genome Atlas) MIBC cohort (n=408) revealed that CEP78 was overexpressed in tumor tissues, which was confirmed with fresh-frozen and formalin-fixed paraffin-embedded specimens collected from 28 and 33 MIBC patients, respectively, in the present study. The clinicopathological relevance of CEP78 was further investigated. High CEP78 expression was found to be correlated with non-papillary histological type, luminal, basal-squamous and neuronal molecular subtypes, TP53 mutation, RB1 mutation, wild-type FGFR3, PPARG fusion and amplification, high total number of single-nucleotide variants, and high neoantigen load, but it was not associated with tumor stages or overall survival. CONCLUSIONS The results of this study suggest that CEP78 plays in a role in promoting the development of MIBC and could be a novel diagnostic and therapeutic target.
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http://dx.doi.org/10.12659/MSM.925197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607667PMC
October 2020

Esomeprazole overcomes paclitaxel-resistance and enhances anticancer effects of paclitaxel by inducing autophagy in A549/Taxol cells.

Cell Biol Int 2021 Jan 20;45(1):177-187. Epub 2020 Oct 20.

The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research & Jiangsu Cancer Hospital, Nanjing, Jiangsu, China.

Non-small-cell lung cancer (NSCLC) is one of the most common malignancies, and the occurrence of drug-resistance severely limits the efficacy of anticancer drugs in the treatment of NSCLC. Identification of new agents to reverse drug-resistance in NSCLC treatment is of great importance and urgency both clinically and scientifically. In the present study, we found that A549/Taxol cells displayed a high level of resistance to paclitaxel with the resistance index up to 231. Importantly, esomeprazole could potentiate the antiproliferative effect of paclitaxel in A549/Taxol cells, but not in A549 cells. Further exploration on the underlying mechanisms revealed that esomeprazole decreased the intracellular pH via inhibiting V-ATPase expression in A549/Taxol cells. Meanwhile, esomeprazole pretreatment significantly promoted paclitaxel-induced polymerization of tubulin and enhanced the proportion of G2/M-arrested cells in A549/Taxol cells. Unfortunately, esomeprazole could only result in a slight decrease in the expression of P-gp in A549/Taxol cells. Interestingly, esomeprazole significantly increased paclitaxel-induced apoptosis, which was impeded by the autophagy inhibitor 3-MA in A549/Taxol cells. Taken together, our data suggest that esomeprazole is a promising chemosensitizer against paclitaxel-resistant NSCLC by inducing autophagy. Our study also offers a new strategy to solve the paclitaxel-resistance problem during NSCLC treatment.
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http://dx.doi.org/10.1002/cbin.11481DOI Listing
January 2021

Extraction optimization, physicochemical properties and antioxidant and hypoglycemic activities of polysaccharides from roxburgh rose (Rosa roxburghii Tratt.) leaves.

Int J Biol Macromol 2020 Dec 28;165(Pt A):517-529. Epub 2020 Sep 28.

College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China; Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Key Lab of Animal Nutrition and Feed Science, Jilin Agricultural University, Changchun 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun 130118, China. Electronic address:

The optimum extraction conditions of polysaccharides from roxburgh rose (Rosa roxburghii Tratt.) leaves (RLP) were obtained by response surface methodology (RSM), which were a liquid to solid ratio of 21.16 mL/g, an extraction temperature of 81.32 °C, and an extraction time of 90.49 min. An RLP yield of 11.04% was obtained under these conditions. DEAE-52 cellulose and Sepharose CL-6B columns were used to purify the RLP, and the purified polysaccharide components RLP-1.2 and RLP-2.1 were obtained. Both RLP-1.2 and RLP-2.1 were composed of galacturonic acid (GalA), glucose (Glc), galactose (Gal), and arabinose (Ara). However, the molar ratios of GalA, Glc, Gal, and Ara in RLP-1.2 and RLP-2.1 were different. At a concentration of 10 mg/mL, the α-amylase inhibitory activities of RLP-1.2 and RLP-2.1 reached 80.74% and 89.85% that of acarbose, respectively, and the α-glucosidase inhibitory activity of RLP-1.2 reached 87.91% that of acarbose. In addition, both RLP-1.2 and RLP-2.1 showed good antioxidant activity. These results suggested that RLP-1.2 and RLP-2.1 possess potential as natural hypoglycemic agents or natural antioxidants.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.198DOI Listing
December 2020

Integrative clinical and molecular analysis of advanced biliary tract cancers on immune checkpoint blockade reveals potential markers of response.

Clin Transl Med 2020 Aug;10(4):e118

Department of Abdominal Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China.

Background: While there have been encouraging preliminary clinical results for immune checkpoint inhibitors (ICIs) in BTCs, it remains a challenge to identify the subset of patients who may benefit. In this study, we evaluated the efficacy of ICI treatment in patients with advanced BTCs, and explored potential biomarkers that are predictive of response.

Methods: The study enrolled 26 patients with advanced microsatellite stable BTCs (15 with gallbladder cancers [GCs] and 11 with intrahepatic cholangiocarcinoma [ICCs]) who received ICI treatment. Targeted next-generation sequencing (NGS) was performed on tumor tissue samples collected from 17 patients. Clinical and genomic characteristics were assessed for the correlation with clinical outcome.

Results: Analysis of the baseline clinical characteristics showed that performance score (PS) of 0 was associated with a better prognosis than PS of 1 (HR = 1.08 × 10 ; 95% CI, 0∼Inf; P = .002). No significant correlations were found between clinical outcome and inflammation-related indicators. NGS profiling of the available tumor tissues, revealed largely non-overlapping somatic alterations between GCs and ICCs. Mutations in LRP1B (HR = 0.26; 95% CI, 0.06-1.21; P = .067), ERBB2 (HR = 0.15; 95% CI, 0.02-1.19; P = .04), or PKHD1 (HR < 0.01; 95% CI, 0-Inf; P = .04) showed strong association with increased progression-free survival (PFS) benefit. Subsequent analysis showed that alterations in the RTK-RAS pathway were associated with improved outcomes (HR = 0.12; 95% CI, 0.02-0.63; P = .003). Tumor mutation burden (TMB) was higher in patients with GC than those with ICC, and was associated with LRP1B mutations (P = .032). We found that patients with 19q amplification (19q Amp) and 9p deletion (9p Del) had poor PFS outcome (19q Amp, HR = 15.4; 95% CI, 2.7-88.5; P < .001; 9p Del; HR = 4.88 × 10 ; 95% CI, 0-Inf; P < .001), while those with chromosomal instability derived PFS benefit (HR = 0.24; 95% CI, 0.05-1.17; P = .057).

Conclusion: Our study identified several potential clinical and genomic features that may serve as biomarkers of clinical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification.
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http://dx.doi.org/10.1002/ctm2.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423188PMC
August 2020

Effect of hypoxia-inducible factor-prolyl hydroxylase inhibitors on anemia in patients with CKD: a meta-analysis of randomized controlled trials including 2804 patients.

Ren Fail 2020 Nov;42(1):912-925

Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are orally active first-in-class new generation drugs for renal anemia. This extensive meta-analysis of randomized controlled trials (RCTs) was designed to provide clear information on the efficacy and safety of HIF-PHIs on anemia in chronic kidney disease (CKD) patients. Searches included PubMed, Web of Science, Ovid MEDLINE, and Cochrane Library database up to October 2019. RCTs of patients with CKD comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in the treatment of anemia. The primary outcome was hemoglobin change from baseline (Hb CFB); the secondary outcomes included iron-related parameters and the occurrence of each adverse event. 26 trials in 17 articles were included, with a total of 2804 dialysis or patients with CKD. HIF-PHIs treatment produced a significant beneficial effect on Hb CFB compared with the placebo group (MD, 0.69; 95% CI, 0.36 to 1.02). However, this favored effect of HIF-PHIs treatment was not observed in subgroup analysis among trials compared with ESAs (MD, 0.06; 95% CI, -0.20 to 0.31). The significant reduction in hepcidin by HIF-PHIs was observed in all subgroups when compared with the placebo group, whereas this effect was observed only in NDD-CKD patients when compared with ESAs. HIF-PHIs increased the risk of nausea (RR, 2.20; 95% CI, 1.06 to 4.53) and diarrhea (RR, 1.75; 95% CI, 1.06 to 2.92). We conclude that orally given HIF-PHIs are at least as efficacious as ESAs treatment to correct anemia short term in patients with CKD. In addition, HIF-PHIs improved iron metabolism and utilization in patients with CKD.
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http://dx.doi.org/10.1080/0886022X.2020.1811121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946011PMC
November 2020

The Construction and Analysis of ceRNA Network and Patterns of Immune Infiltration in Colon Adenocarcinoma Metastasis.

Front Cell Dev Biol 2020 4;8:688. Epub 2020 Aug 4.

Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Colon adenocarcinoma (COAD) is a malignant and lethal tumor in digestive system and distance metastasis lead to poor prognosis. The metastasis-specific ceRNAs (competitive endogenous RNAs) and tumor-infiltrating immune cells might associate with tumor prognosis and distance metastasis. Nonetheless, few studies have concentrated on ceRNAs and Immune cells in COAD.

Methods: The gene expression profile and clinical information of COAD were downloaded from TCGA and divided into two groups: primary tumors with or without distance metastasis. We applied comprehensive bioinformatics methods to analyze differential expression genes (DEGs) related to metastasis and establish the ceRNA networks. The Cox analysis and Lasso regression were utilized to screen the pivotal genes and prevent overfitting. Based on them, the prognosis prediction nomograms were established. The cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was then applied to screen significant tumor immune-infiltrating cells associated with COAD metastasis and established another prognosis prediction model. Ultimately, co-expression analysis was applied to explore the relationship between key genes in ceRNA networks and significant immune cells. Multiple databases and preliminary clinical specimen validation were used to test the expressions of key biomarkers at the cellular and tissue levels.

Results: We explored 1 significantly differentially expressed lncRNA, 1 significantly differentially expressed miRNA, 8 survival-related immune-infiltrating cells, 5 immune cells associated with distance metastasis. Besides, 3 pairs of important biomarkers associated with COAD metastasis were also identified: T cells follicular helper and hsa-miR-125b-5p ( = -0.200, < 0.001), Macrophages M0 and hsa-miR-125b-5p ( = 0.170, < 0.001) and Macrophages M0 and FAS ( = -0.370, < 0.001). Multidimensional validation and preliminary clinical specimen validation also supported the results.

Conclusion: In this research, we found some significant ceRNAs (FAS and hsa-miR-125b-5p) and tumor-infiltrating immune cells (T cells follicular helper and Macrophages M0) might related to distance metastasis and prognosis of COAD. The nomograms could assist scientific and medical researchers in clinical management.
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http://dx.doi.org/10.3389/fcell.2020.00688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417319PMC
August 2020

Fine Particulate Air Pollution, Public Service, and Under-Five Mortality: A Cross-Country Empirical Study.

Healthcare (Basel) 2020 Aug 14;8(3). Epub 2020 Aug 14.

School of Economics and Management, Beijing Forestry University, Beijing 100083, China.

The impacts of fine particulate matter (PM) air pollution on health outcomes, especially those of children, have attracted worldwide attention. Based on the PM concentration data of 94 countries, including the least developed countries estimated by satellite observations in nearly 20 years, this paper investigated the impacts of PM pollution on under-five mortality rate (U5MR) and analyzed the role of public service in moderating the PM-mortality relationship. Results indicated that PM pollution had significantly positive influence on U5MR globally. However, the effects of fine particulate pollution on child mortality were heterogeneous in terms of their significance and degrees in countries with different levels of development. A further test based on panel threshold model revealed that public service, measured by public education spending and sanitation service, played a positive moderating role in the PM-mortality relationship. Specifically, when the ratio of public education expenditure in GDP of a country exceeded the first threshold value 3.39% and the second threshold value 5.47%, the magnitude of the impacts of PM pollution on U5MR significantly decreased accordingly. When the percentage of population with access to improved sanitation facilities in a country was over 41.3%, the health damaging effects were reduced by more than half. This paper fills the current gap of PM research in least developed countries and provides key policy recommendations.
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http://dx.doi.org/10.3390/healthcare8030271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551449PMC
August 2020

Correlation Between Hemoglobin Levels and the Prognosis of First-Line Chemotherapy in Patients with Advanced Gastric Cancer.

Cancer Manag Res 2020 7;12:7009-7019. Epub 2020 Aug 7.

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou 310022, People's Republic of China.

Background: This retrospective study evaluated the prognostic significance of hemoglobin (Hb) levels in patients (pts) with unresectable locally advanced or metastatic gastric cancer who have not previously received chemotherapy.

Patients And Methods: We screened 249 pts with advanced gastric cancer, who were categorized into four groups, namely, non-anemia (normal Hb levels), mild (10 g/dl to normal), moderate (8-10 g/dl), and severe anemia groups (<8 g/dl), to study the prognostic significance of Hb levels. We also examined the correlation between changes in Hb levels and treatment effects via imaging during the treatment course.

Results: The objective response rate (ORR) was 47.4% for pts with anemia versus 43.4% for pts without anemia (=0.536). Hemoglobin levels were reduced by 0.51 ± 1.86 and 1.93 ± 1.33 g/dl after chemotherapy versus before chemotherapy in the disease control group and progressive groups, respectively (P=0.002). The median progression-free survival (mPFS) of first-line chemotherapy in all pts was 6.3 months. Specifically, the mPFS was 5.7 months in pts with severe anemia, compared with 6.4 months for pts with non-severe anemia (Hb≥8g/dl). The median overall survival (mOS) of all pts was 14.0 months. In particular, the mOS was 15.0 months for pts with non-anemia and mild anemia (Hb≥10g/dl) versus 11.5 months for pts with moderate or severe anemia. In multivariate analysis, ascites and decreased Hb post-chemotherapy were identified as independent prognostic indicators for PFS and OS.

Conclusion: Our findings indicate that Hb levels are associated with the prognosis in the first-line chemotherapy for pts with advanced gastric cancer. Pts with progressive disease experience a larger decrease in Hb levels, and those with baseline Hb levels ≥10 g/dl experience longer OS.
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http://dx.doi.org/10.2147/CMAR.S256074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423215PMC
August 2020