Publications by authors named "Zhihua Chen"

255 Publications

Structure-Aware Motion Deblurring Using Multi-Adversarial Optimized CycleGAN.

IEEE Trans Image Process 2021 9;30:6142-6155. Epub 2021 Jul 9.

Recently, Convolutional Neural Networks (CNNs) have achieved great improvements in blind image motion deblurring. However, most existing image deblurring methods require a large amount of paired training data and fail to maintain satisfactory structural information, which greatly limits their application scope. In this paper, we present an unsupervised image deblurring method based on a multi-adversarial optimized cycle-consistent generative adversarial network (CycleGAN). Although original CycleGAN can handle unpaired training data well, the generated high-resolution images are probable to lose content and structure information. To solve this problem, we utilize a multi-adversarial mechanism based on CycleGAN for blind motion deblurring to generate high-resolution images iteratively. In this multi-adversarial manner, the hidden layers of the generator are gradually supervised, and the implicit refinement is carried out to generate high-resolution images continuously. Meanwhile, we also introduce the structure-aware mechanism to enhance the structure and detail retention ability of the multi-adversarial network for deblurring by taking the edge map as guidance information and adding multi-scale edge constraint functions. Our approach not only avoids the strict need for paired training data and the errors caused by blur kernel estimation, but also maintains the structural information better with multi-adversarial learning and structure-aware mechanism. Comprehensive experiments on several benchmarks have shown that our approach prevails the state-of-the-art methods for blind image motion deblurring.
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http://dx.doi.org/10.1109/TIP.2021.3092814DOI Listing
July 2021

Epithelium-derived IL17A Promotes Cigarette Smoke-induced Inflammation and Mucus Hyperproduction.

Am J Respir Cell Mol Biol 2021 Jun 29. Epub 2021 Jun 29.

Zhejiang University School of Medicine, 26441, Respiratory Medicine, Hangzhou, China;

Airway epithelium is a central modulator of innate and adaptive immunity in the lung. Interleukin (IL)17A expression was found to be increased in airway epithelium; however, the role of epithelial-derived IL17A in chronic obstructive pulmonary disease (COPD) remains unclear. In this study, we aim to determine whether epithelial-derived IL17A regulates inflammation and mucus hyperproduction in COPD using a cultured human bronchial epithelial (HBE) cell line in vitro and airway epithelium IL17A-specific knockout mouse in vivo. Increased IL17A expression was observed in mouse airway epithelium upon cigarette smoke (CS) exposure or in a COPD mouse model that was induced by CS and elastin. CS extract (CSE) also triggered IL17A expression in HBE cells. Blocking IL17A or IL17RA effectively attenuated CSE-induced MUC5AC and the inflammatory cytokines IL6, tumor necrosis factor (TNF)-α, and IL1β in HBE cells, suggesting that IL17A mediates CSE-induced inflammation and mucin production in an autocrine manner. CSE activated p-JUN and p-JNK, which were also reduced by IL17RA-siRNA, and JUN-siRNA attenuated CSE-induced IL6 and MUC5AC. In vivo, selective knockout of IL17A in airway epithelium markedly reduced the neutrophilic infiltration in Bronchoalveolar Lavage Fluid (BALF), peribronchial inflammation, pro-inflammatory mediators (CXCL1 and CXCL2), and mucus production in a COPD mouse model. We showed a novel function of airway epithelium-derived IL17A, which can act locally in an autocrine manner to amplify inflammation and increase mucus production in COPD pathogenesis.
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http://dx.doi.org/10.1165/rcmb.2020-0424OCDOI Listing
June 2021

Morphologic and molecular correlates of EZH2 as a predictor of platinum resistance in high-grade ovarian serous carcinoma.

BMC Cancer 2021 Jun 17;21(1):714. Epub 2021 Jun 17.

Department of Pathology, Moffitt Cancer Center, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA.

Background: Enhancer of zesta homologue 2 (EZH2) is an essential component of polycomb repressive complex 2 (PRC2) that contributes to tumor progression and chemo-resistance. The aim of this study was to comprehensively assess the prognostic value of EZH2 across the morphologic and molecular spectra of high-grade serous ovarian carcinoma (HGSOC) by utilizing both immunohistochemistry (IHC) and proteogenomic technologies.

Methods: IHC of EZH2 was performed using a tissue microarray of 79 HGSOC scored (+/-) for lymphovascular invasion (LVI), tumor-infiltrating lymphocytic aggregates ≥1 mm (TIL) and architectural growth patterns. The association of EZH2 H-score with response to therapy and overall survival was evaluated by tumor features. We also evaluated EZH2 transcriptional (RNA sequencing) and protein (mass spectrometry) expression from bulk tumor samples from 336 HGSOC from The Cancer Genome Atlas (TCGA). EZH2 expression and co-expression networks were compared by clinical outcomes.

Results: For HGSOC without TIL (58%), EZH2 expression was almost 2-fold higher in platinum resistant tumors (P = 0.01). Conversely, EZH2 was not associated with platinum resistance among TIL+ HGSOC (P = 0.41). EZH2 expression was associated with reduced survival for tumors with LVI (P = 0.04). Analysis of TCGA found higher EZH2 expression in immunoreactive and proliferative tumors (P = 6.7 × 10) although protein levels were similar across molecular subtypes (P = 0.52). Both mRNA and protein levels of EZH2 were lower in platinum resistant tumors although they were not associated with survival. Co-expression analysis revealed EZH2 networks totaling 1049 mRNA and 448 proteins that were exclusive to platinum sensitive or resistant tumors. The EZH2 network in resistant HGSOC included CARM1 which was positively correlated with EZH2 at both mRNA (r = 0.33, p = 0.003) and protein (r = 0.14, P = 0.01) levels. Further, EZH2 co-expression with CARM1 corresponded to a decreased prognostic significance of EZH2 expression in resistant tumors.

Conclusions: Our findings demonstrate that EZH2 expression varies based on its interactions with immunologic pathways and tumor microenvironment, impacting the prognostic interpretation. The association between high EZH2 expression and platinum resistance in TIL- HGSOC warrants further study of the implications for therapeutic strategies.
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http://dx.doi.org/10.1186/s12885-021-08413-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212453PMC
June 2021

The effect of nursing intervention based on the staged behaviour change on recovery, quality of life, and self-efficacy of diabetic patients with scalds.

Int Wound J 2021 Jun 2. Epub 2021 Jun 2.

Department of Burn and Plastic Surgery, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

This study aimed to explore the impact of nursing intervention based on staged behaviour change (SBC) on the quality of life (QoL) and self-efficacy of diabetic patients with scalds. From January 2020 to January 2021, a total of 82 consecutive cases with diabetes and scalds were prospectively enrolled in this study. They were divided into the SBC group (41 cases were given SBC-based nursing intervention) and the control group (41 cases were given routine intervention) using the random number table method. The granulation tissue growth time and wound healing time were compared between the two groups. Pain intensity, QoL, self-efficacy, and score of wound exudation at 3, 7, and 15 days after intervention were observed. The granulation tissue growth time and wound healing time of the SBC group were lower than those of the control group with statistical difference (P < 0.05). The 3-, 5-, and 7-day pain intensity of the SBC group were all lower than those of the control group, with statistical difference (P < 0.05, respectively). Before intervention, there were no significant differences in mental health, role emotional, social function, vitality status, physical pain, role physical, physical function, and general health between the two groups (P > 0.05, respectively). After intervention, the above indicators of the SBC group were significantly higher than those of the control group (P < 0.05, respectively). Before intervention, there were no significant differences between the two groups in communication with doctors, emotional communication, role function, symptom management, medication as prescribed, and control of water and salt intake and nutrition (P > 0.05, respectively). After intervention, the above indicators in the SBC group were all significantly higher than those in the control group (P < 0.05, respectively). The score of wound exudation of the SBC group was lower than that of the control group after intervention (P < 0.05). SBC-based nursing intervention can effectively improve the QoL and self-efficacy of diabetic patients with scalds and can effectively promote wound healing, and can be recommended for clinical use.
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http://dx.doi.org/10.1111/iwj.13622DOI Listing
June 2021

IL-17-Mediated Inflammation Promotes Cigarette Smoke-Induced Genomic Instability.

Cells 2021 May 12;10(5). Epub 2021 May 12.

Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.

(1) Background: Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process have yet to be elucidated. (2) Methods: In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. (3) Results: Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissues of smokers than in those of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides this, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. (4) Conclusions: These results suggest that cigarette smoke induces genomic instability at least partially through IL-17-mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.
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http://dx.doi.org/10.3390/cells10051173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151076PMC
May 2021

Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth.

Sci Adv 2021 May 26;7(22). Epub 2021 May 26.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Compelling evidence suggests that inflammatory components contribute to cancer development. However, eosinophils, involved in several inflammatory diseases, were not fully explored in cancer metastasis. We show that airway inflammatory eosinophilia and colonic inflammation with eosinophil infiltration are both associated with increased metastasis in mice. Eosinophilia is responsible for increased bone metastasis in eosinophil-enriched δ transgenic ( Tg) mice. We also observe increased eosinophils in the malignant pleural effusion of cancer patients with pleural metastasis. Mechanistically, eosinophils promote tumor cell migration and metastasis formation through secreting C-C motif chemokine ligand 6 (CCL6). Genetic knockout of in Tg mice remarkably attenuates bone metastasis. Moreover, inhibition of C-C chemokine receptor 1 (CCR1, the receptor of CCL6) in tumor cells reduces tumor cell migration and metastasis. Thus, our study identifies a CCL6-dependent prometastatic activity of eosinophils, which can be inhibited by targeting CCR1 and represent an approach to preventing metastatic disease.
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http://dx.doi.org/10.1126/sciadv.abb5943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153717PMC
May 2021

Single-Cell Characterization of the Immune Microenvironment of Melanoma Brain and Leptomeningeal Metastases.

Clin Cancer Res 2021 Jul 25;27(14):4109-4125. Epub 2021 May 25.

The Department of Tumor Biology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.

Purpose: Melanoma brain metastases (MBM) and leptomeningeal melanoma metastases (LMM) are two different manifestations of melanoma CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape of MBM, LMM, and melanoma skin metastases.

Experimental Design: scRNA-seq was undertaken on 43 patient specimens, including 8 skin metastases, 14 MBM, and 19 serial LMM specimens. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by IHC and flow cytometry. Association analyses were undertaken to identify immune cell subsets correlated with overall survival.

Results: The LMM microenvironment was characterized by an immune-suppressed T-cell landscape distinct from that of brain and skin metastases. An LMM patient with long-term survival demonstrated an immune repertoire distinct from that of poor survivors and more similar to normal cerebrospinal fluid (CSF). Upon response to PD-1 therapy, this extreme responder showed increased levels of T cells and dendritic cells in their CSF, whereas poor survivors showed little improvement in their T-cell responses. In MBM patients, therapy led to increased immune infiltrate, with similar T-cell transcriptional diversity noted between skin metastases and MBM. A correlation analysis across the entire immune landscape identified the presence of a rare population of dendritic cells (DC3) that was associated with increased overall survival and positively regulated the immune environment through modulation of activated T cells and MHC expression.

Conclusions: Our study provides the first atlas of two distinct sites of melanoma CNS metastases and defines the immune cell landscape that underlies the biology of this devastating disease.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282775PMC
July 2021

mTOR regulates GPVI-mediated platelet activation.

J Transl Med 2021 05 10;19(1):201. Epub 2021 May 10.

Chronic Disease Research Institute, Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, 866 Yu-Hang-Tang Road, Hangzhou, 310058, China.

Background: Due to mTOR (mammalian/mechanistic target of rapamycin) gene-loss mice die during embryonic development, the role of mTOR in platelets has not been evaluated using gene knockout technology.

Methods: A mouse model with megakaryocyte/platelet-specific deletion of mTOR was established, and be used to evaluate the role of mTOR in platelet activation and thrombus formation.

Results: mTOR platelets were deficient in thrombus formation when grown on low-concentration collagen-coated surfaces; however, no deficiency in thrombus formation was observed when mTOR platelets were perfused on higher concentration collagen-coated surfaces. In FeCl-induced mouse mesenteric arteriole thrombosis models, wild-type (WT) and mTOR mice displayed significantly different responses to low-extent injury with respect to the ratio of occluded mice, especially within the first 40 min. Additionally, mTOR platelets displayed reduced aggregation and dense granule secretion (ATP release) in response to low doses of the glycoprotein VI (GPVI) agonist collagen related peptide (CRP) and the protease-activated receptor-4 (PAR4) agonist GYPGKF-NH; these deficiencies were overcame by stimulation with higher concentration agonists, suggesting dose dependence of the response. At low doses of GPVI or PAR agonist, the activation of αβ in mTOR platelets was reduced. Moreover, stimulation of mTOR platelets with low-dose CRP attenuated the phosphorylation of S6K1, S6 and Akt Ser473, and increased the phosphorylation of PKCδ Thr505 and PKCε Ser729. Using isoform-specific inhibitors of PKCs (δ, ɛ, and α/β), we established that PKCδ/ɛ, and especially PKCδ but not PKCα/β or PKCθ, may be involved in low-dose GPVI-mediated/mTOR-dependent signaling.

Conclusion: These observations indicate that mTOR plays an important role in GPVI-dependent platelet activation and thrombus formation.
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http://dx.doi.org/10.1186/s12967-021-02756-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111939PMC
May 2021

Biomass enhances the reduction of oxidized pellets with carbon monoxide.

Bioresour Technol 2021 Jul 13;331:124973. Epub 2021 Mar 13.

Center for Biorefning and Department of Bioproducts and Biosystems Engineering, University of Minnesota, 1390 Eckles Ave., St. Paul, MN 55108, USA.

In this study, the reduction mechanism of using CO to reduce biomass-oxidized pellets (BOP) and general-oxidized pellets (GOP) was deeply analyzed. The effect of biomass addition on the reduction of oxidized pellets and the change of reduction kinetics were studied. The addition of 2 wt% biomass into pellets increases pores of the oxidized pellets, promotes the rate of CO entering the pellets and the overflow of CO, which results in faster reduction of the oxidized pellets. The reduction reactions of BOP and GOP were controlled by internal diffusion, mixing control and interface control sequentially. Also, addition of the biomass to the pellets decreases the activation energy required for their reduction, from 87.30 to 80.65 kJ·mol. The addition of biomass shortens the reduction time by 3% which can reduce the energy consumption. Therefore, the biomass together with CO enhances the reduction of oxidized pellets and has real environmental benefits.
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http://dx.doi.org/10.1016/j.biortech.2021.124973DOI Listing
July 2021

Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.

Aging Cell 2021 03 3;20(3):e13323. Epub 2021 Mar 3.

Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, USA.

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10 ) and BMPER (rs17169634; p = 1.45 × 10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.
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http://dx.doi.org/10.1111/acel.13323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963337PMC
March 2021

Targeted Therapy Given after Anti-PD-1 Leads to Prolonged Responses in Mouse Melanoma Models through Sustained Antitumor Immunity.

Cancer Immunol Res 2021 May 2;9(5):554-567. Epub 2021 Mar 2.

The Department of Tumor Biology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.

Immunotherapy (IT) and targeted therapy (TT) are both effective against melanoma, but their combination is frequently toxic. Here, we investigated whether the sequence of IT (anti-PD-1)→ TT (ceritinib-trametinib or dabrafenib-trametinib) was associated with improved antitumor responses in mouse models of and -mutant melanoma. Mice with mutant (SW1) or -mutant (SM1) mouse melanomas were treated with either IT, TT, or the sequence of IT→TT. Tumor volumes were measured, and samples from the -mutant melanomas were collected for immune-cell analysis, single-cell RNA sequencing (scRNA-seq), and reverse phase protein analysis (RPPA). scRNA-seq demonstrated that the IT→TT sequence modulated the immune environment, leading to increased infiltration of T cells, monocytes, dendritic cells and natural killer cells, and decreased numbers of tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells. Durable responses to the IT→TT sequence were dependent on T-cell activity, with depletion of CD8, but not CD4, T cells abrogating the therapeutic response. An analysis of transcriptional heterogeneity in the melanoma compartment showed the sequence of IT→TT enriched for a population of melanoma cells with increased expression of MHC class I and melanoma antigens. RPPA analysis demonstrated that the sustained immune response induced by IT→TT suppressed tumor-intrinsic signaling pathways required for therapeutic escape. These studies establish that upfront IT improves the responses to TT in and -mutant melanoma models.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102376PMC
May 2021

Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation.

Signal Transduct Target Ther 2021 Feb 28;6(1):91. Epub 2021 Feb 28.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.

Eosinophils are terminally differentiated cells derived from hematopoietic stem cells (HSCs) in the bone marrow. Several studies have confirmed the effective roles of eosinophils in asthmatic airway pathogenesis. However, their regulatory functions have not been well elucidated. Here, increased C-C chemokine ligand 6 (CCL6) in asthmatic mice and the human orthologs CCL15 and CCL23 that are highly expressed in asthma patients are described, which are mainly derived from eosinophils. Using Ccl6 knockout mice, further studies revealed CCL6-dependent allergic airway inflammation and committed eosinophilia in the bone marrow following ovalbumin (OVA) challenge and identified a CCL6-CCR1 regulatory axis in hematopoietic stem cells (HSCs). Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist BX471. Thus, the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation, which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors (GPCRs) for future clinical treatment of asthma.
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http://dx.doi.org/10.1038/s41392-021-00482-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914252PMC
February 2021

Development and Multi-Data Set Verification of an RNA Binding Protein Signature for Prognosis Prediction in Glioma.

Front Med (Lausanne) 2021 9;8:637803. Epub 2021 Feb 9.

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Increasing evidence emphasizes the clinical implications of RNA binding proteins (RBPs) in cancers. This study aimed to develop a RBP signature for predicting prognosis in glioma. Two glioma datasets as training ( = 693) and validation ( = 325) sets were retrieved from the CGGA database. In the training set, univariate Cox regression analysis was conducted to screen prognosis-related RBPs based on differentially expressed RBPs between WHO grade II and IV. A ten-RBP signature was then established. The predictive efficacy was evaluated by ROCs. The applicability was verified in the validation set. The pathways involving the risk scores were analyzed by ssGSEA. scRNA-seq was utilized for evaluating their expression in different glioma cell types. Moreover, their expression was externally validated between glioma and control samples. Based on 39 prognosis-related RBPs, a ten RBP signature was constructed. High risk score distinctly indicated a poorer prognosis than low risk score. AUCs were separately 0.838 and 0.822 in the training and validation sets, suggesting its well performance for prognosis prediction. Following adjustment of other clinicopathological characteristics, the signature was an independent risk factor. Various cancer-related pathways were significantly activated in samples with high risk score. The scRNA-seq identified that risk RBPs were mainly expressed in glioma malignant cells. Their high expression was also found in glioma than control samples. This study developed a novel RBP signature for robustly predicting prognosis of glioma following multi-data set verification. These RBPs may affect the progression of glioma.
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http://dx.doi.org/10.3389/fmed.2021.637803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900154PMC
February 2021

Pattern and degree of groundwater recharge from river leakage in a karst canyon area under intensive mine dewatering.

Sci Total Environ 2021 Jun 29;774:144921. Epub 2021 Jan 29.

Yiliang Chihong Mining Co., Ltd., Zhaotong 657600, China.

Most lead-zinc (Pb-Zn) deposits in southwestern China located in karst canyon areas are faced with difficulties to identify the connection between surface water and groundwater. Hydrological dynamics monitoring, tracer injection test, and riverbed dredging test were applied to discuss the contribution of river leakage to the mining area under intensive mine dewatering. The water level of surface water (~887 m asl), pore groundwater (~886 m asl), and karst groundwater (882-886 m asl) decreased in turn in the Maoping Pb-Zn deposit, which suggested the Luoze River as a losing stream. The groundwater temperature dynamics did not respond to rainfall events. Karst groundwater presented a peak delay and amplitude decay when compared with the overlying pore groundwater. Lower electrical conductivity (40-70 μS/cm) was generated due to cation exchange process during vertical infiltration. It could be concluded firstly that pore groundwater ran horizontally and rapidly according to the synchronous response within an hour of groundwater level in the upstream and downstream boreholes to riverbed dredging test. Secondly, pore groundwater could supply the underlying karst groundwater vertically and slowly, which caused an increase of groundwater level lasting for one week during the dredging test until the recovery of decreasing trend in the dry season. Finally, the injected tracer cost more than seven months to eliminate, indicating a slow velocity around 0.01 m/d in the karst aquifer. Overall, it could be proved that surface water could be an indirect and limited water-filling source for the karst groundwater in the mining area under the control of the riverbed sediment structure. Despite the significant groundwater level drawdown caused by intensive mine dewatering, the mining area would not be threatened by the possible river leakage, and the river ecological system would not be reshaped greatly due to the weak interaction process between surface water and groundwater.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144921DOI Listing
June 2021

Characterization of the human skin resistome and identification of two microbiota cutotypes.

Microbiome 2021 02 17;9(1):47. Epub 2021 Feb 17.

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, and Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Background: The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity.

Results: In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as Staphylococcus spp, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria ("superbugs") existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified Moraxella osloensis as a species specific for Chinese skin. Importantly, Moraxella osloensis proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with Cutibacterium acnes indicating the second one. Each of such "cutotypes" was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development.

Conclusions: The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00995-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890624PMC
February 2021

Cyanide Ion-Promoted Nucleophilic Displacement of Aromatic Nitro Groups: A Mild, One-Pot, Transition Metal-Free Synthesis of Nitrile-Containing Naphthalimide Aryl Ether Derivatives.

J Org Chem 2021 Feb 12;86(3):3059-3064. Epub 2021 Jan 12.

School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, P. R. China.

Herein we report the novel synthesis of nitrile-containing naphthalimide aryl ether derivatives via transition metal-free cyanide ion-promoted nucleophilic displacement of nitronaphthalimide with alcohols or phenols. The transformation involves a one-pot reaction, which is operationally simple and mild and bereft of transition metal catalysts. This work provides a novel route for the preparation of diaryl ether derivatives.
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http://dx.doi.org/10.1021/acs.joc.0c02598DOI Listing
February 2021

Self-Supported Reduced Graphene Oxide Membrane and Its Cu Adsorption Capability.

Materials (Basel) 2020 Dec 31;14(1). Epub 2020 Dec 31.

College of Textile and Clothing Engineering, Soochow University, Suzhou 215006, China.

Graphene stratiform membrane materials have been recently applied to heavy metal removal in aqueous systems via adsorption due to their high mechanical strength, chemical stability, and other properties. We applied reduced graphene oxide (rGO) alone as an adsorbent to remove heavy metal ions from wastewater. Self-supported rGO membrane was prepared using a green reduction method with sodium hydrosulfite. We used the Raman spectra to observe the structure of the rGO membrane. The morphology of the self-supported membrane was measured by a scanning electron microscope. The Cu adsorption performance was measured in terms of pH, reaction time, metal ion concentration, and temperature. The maximum Cu adsorption capacity of the rGO membrane was found to be 149.25 mg/g. The adsorption process followed a pseudo-second-order kinetic model, and adsorption isotherms were simulated by the Freundlich model.
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http://dx.doi.org/10.3390/ma14010146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794842PMC
December 2020

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Cancer Epidemiol Biomarkers Prev 2021 01 3;30(1):217-228. Epub 2020 Nov 3.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.

Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers ( = 0.43, = 2.66 × 10). We found seven loci associated with risk for both cancers ( < 2.4 × 10). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified ( < 5 × 10). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.

Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.

Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0739DOI Listing
January 2021

Enhanced adsorption of tetracycline by an iron and manganese oxides loaded biochar: Kinetics, mechanism and column adsorption.

Bioresour Technol 2021 Jan 26;320(Pt A):124264. Epub 2020 Oct 26.

School of Environment, Henan Normal University, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Xinxiang 453007, China.

A Fe/Mn oxides loaded biochar (FeMn-BC) was prepared to enhance the adsorption of tetracycline (TC). γ-FeO and MnO were assigned to the Fe and Mn oxides, respectively. The enhanced adsorption of TC was dominated by the loaded γ-FeO and MnO. According to Akaike-Information-Criteria evaluation, Elovich kinetic and Langmuir isotherm models could best describe the adsorption with a maximum capacity of 14.24 mg/g. During adsorption process, the γ-FeO and MnO hydrolyzed into hydroxides (FeOOH and MnOOH) which acted as bases to complex with TC ion under alkaline condition (pH = 11). After the adsorption, the concentrations of leached Fe and Mn could meet the requirements PRC standards GB13456-2012 and GB8978-1996, respectively. The FeMn-BC had ~24% on TC removal (initial concentration of 20 mg/L) after four-cycles regeneration. The FeMn-BC was also available for TC adsorptions in column tests and actual wastewater.
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http://dx.doi.org/10.1016/j.biortech.2020.124264DOI Listing
January 2021

MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation.

Thorax 2020 12 18;75(12):1047-1057. Epub 2020 Oct 18.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Introduction: Airway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)-autophagy axis in airway epithelial injury in asthma.

Methods: We examined the MTOR-autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related mice were used for allergic models.

Results: MTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice.

Conclusion: Collectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.
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http://dx.doi.org/10.1136/thoraxjnl-2019-213771DOI Listing
December 2020

Mutation Revealed from Myofibroblastoma-Discordant Monozygotic Twins Leads to p53/p21 Deficit and WEE1 Inhibitor Sensitivity.

Adv Sci (Weinh) 2020 Oct 5;7(19):2001041. Epub 2020 Aug 5.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 310009 China.

High-throughput gene sequencing has identified various genetic variants as the culprits for some common hereditary cancers. However, the heritability of a substantial proportion of cancers remains unexplained, which may result from rare deleterious mutations hidden in a myriad of nonsense genetic variations. This poses a great challenge to the understanding of the pathology and thus the rational design of effective treatments for affected patients. Here, whole genome sequencing is employed in a representative case in which one monozygotic twin is discordant for lung inflammatory myofibroblastoma to disclose rare tumor-related mutations. A missense single nucleotide variation rs61955126 T>C in the lysine methyltransferase SETD8 (accession: NM_020382, ) is exposed. It is shown that SETD8 is vital for genomic integrity by promoting faithful DNA replication, and its C302R mutation downregulates the p53/p21 pathway. Importantly, the mutation significantly increases the sensitivity of cancer cells to WEE1 inhibition. Given that WEE1 inhibitors have shown great promise for clinical approval, these results impart a potential therapeutic approach using WEE1 inhibitor for cancer patients carrying the same mutation, and indicate that genome sequencing and genetic functional studies can be integrated into individualized therapies.
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http://dx.doi.org/10.1002/advs.202001041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539211PMC
October 2020

Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) promotes glioblastoma cell invasion in the brain microenvironment.

Oncogene 2020 12 10;39(50):7253-7264. Epub 2020 Oct 10.

Departments of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Glioblastoma (GBM), or grade IV astrocytoma, is a malignant brain cancer that contains subpopulations of proliferative and invasive cells that coordinately drive primary tumor growth, progression, and recurrence after therapy. Here, we have analyzed functions for megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1), an eight-transmembrane protein normally expressed in perivascular brain astrocyte end feet that is essential for neurovascular development and physiology, in the pathogenesis of GBM. We show that Mlc1 is expressed in human stem-like GBM cells (GSCs) and is linked to the development of primary and recurrent GBM. Genetically inhibiting MLC1 in GSCs using RNAi-mediated gene silencing results in diminished growth and invasion in vitro as well as impaired tumor initiation and progression in vivo. Biochemical assays identify the receptor tyrosine kinase Axl and its intracellular signaling effectors as important for MLC1 control of GSC invasive growth. Collectively, these data reveal key functions for MLC1 in promoting GSC growth and invasion, and suggest that targeting the Mlc1 protein or its associated signaling effectors may be a useful therapy for blocking tumor progression in patients with primary or recurrent GBM.
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http://dx.doi.org/10.1038/s41388-020-01503-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736299PMC
December 2020

Identification and Estimation of Solute Storage and Release in Karst Water Systems, South China.

Int J Environ Res Public Health 2020 10 2;17(19). Epub 2020 Oct 2.

School of Environmental Studies, China University of Geosciences, Wuhan 430074, China.

Solute storage and release in groundwater are key processes in solute transport for groundwater remediation and protection. In karst areas where concentrated recharge conditions exist, pollution incidents can easily occur in springs that are hydraulically connected to densely inhabited karst depressions. The intrinsic heterogeneity common in karst media makes modeling solute transport very difficult with great uncertainty. Meanwhile, it is noteworthy that solute storage and release within subsurface conduits and fissures exhibit strong controlling function on pollutant attenuation during underground floods. Consequently, in this paper, we identified and estimated the solute storage and release processes in karst water systems under concentrated recharge conditions. The methodology uses the advection-dispersion method and field tracer tests to characterize solute transport in different flow paths. Two solute transport pathways were established (i.e., linear pathway (direct transport through karst conduits) and dynamic pathway (flow through fissures)). Advection-dispersion equations were used to fit the breakthrough curves in conduit flow, while the volume of solute storage in fissures were calculated by segmenting the best fitting curves from the total breakthrough curves. The results show that, greater recharge flow or stronger dynamic conditions leads to lower solute storage rate, with the storage rate values less than 10% at high water level conditions. In addition, longer residence time was recorded for solute exchange between conduits and fissures at the low water level condition, thereby contributing to a higher solute storage rate of 26% in the dynamic pathway.
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http://dx.doi.org/10.3390/ijerph17197219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578940PMC
October 2020

Response of patients with chest tightness variant asthma with routine asthma treatment regimen: A 1-year multicenter, prospective, real-world study.

Clin Transl Med 2020 Sep;10(5):e178

Department of Pulmonary Medicine, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma [CTVA]) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA); however, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear.

Objective: The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long-acting beta-agonists was explored in a 52-week multicenter, prospective, real-world study.

Results: After 52 weeks of treatment with therapy regimens used for CA, the mean 5-point Asthma Control Questionnaire (ACQ-5) score decreased markedly from 1.38(first administration) to 0.71 (52 weeks, mean decrease: 0.674, 95%CI: 0.447-0.900, P<.001).The mean asthma quality-of-life questionnaire (AQLQ) score increased from 5.77 (first administration) to 6.20 (52 weeks, mean increase: 0.441, 95% CI 0.258-0.625, P<.001). Furthermore, at week 52, FVC, FEV %, the diurnal variation in PEFand the PD20-FEV were significantly improved. Subgroup analysis revealed that the patients at first administration in the responsive group had higher ACQ-5 scores than those in the nonresponsive group (P < .05).

Conclusion: In conclusion, patients with CTVA had a good therapeutic response to the guideline-recommended routine treatment (containing inhaled corticosteroids). The association between the treatment response and the severity of CTVA suggested that CTVA patients with higher ACQ-5 scores had better therapeutic effects.
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http://dx.doi.org/10.1002/ctm2.178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503098PMC
September 2020

Heat-sensitive moxibustion self-administration in patients in the community with primary hypertension: A protocol for a multi-center, pragmatic, non-randomized trial.

Medicine (Baltimore) 2020 Sep;99(38):e22230

The Second Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Jiangxi, China.

Background: Although the efficacy of antihypertensive drugs has been well established for primary hypertension, their effectiveness is always limited by side effects and poor compliance. Heat-sensitive moxibustion is an innovative acupoint stimulation therapy that is promising as a community health care intervention for hypertension.

Aims: This study aims to evaluate the pragmatic effectiveness and safety of heat-sensitive moxibustion self-administration by patients in the community with primary hypertension.

Methods: This study will adopt a multi-center, pragmatic, nonrandomized design. Six hundred patients with primary hypertension will be recruited from 4 communities. Each patient will choose to either receive heat-sensitive moxibustion self-administration + original antihypertensive drugs or maintain their original antihypertensive drugs without heat-sensitive moxibustion for 1 year.

Expected Outcomes: The primary outcome will be changes in systolic and diastolic blood pressures and the percentage changes in the doses of antihypertensive drugs. The secondary outcomes will be changes in quality of life assessed by a validated patient-reported outcome scale and the levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urinary albumin, and serum creatinine. The proportion of patients with poor compliance with the heat-sensitive moxibustion regimen will also be evaluated as a secondary outcome. The safety of heat-sensitive moxibustion will be considered by analyzing the incidence of all and serious adverse events and their correlation with heat-sensitive moxibustion.

Discussion: The findings of this study will provide pragmatic evidence for heat-sensitive moxibustion self-administration in patients in the community with primary hypertension and may also establish an ethical basis for further randomized controlled trials.

Trial Registration: The protocol of this trial was registered in ClinicalTrials.gov at May 11, 2020 (No. NCT04381520).
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http://dx.doi.org/10.1097/MD.0000000000022230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505380PMC
September 2020

Control strategy of stable walking for a hexapod wheel-legged robot.

ISA Trans 2021 Feb 14;108:367-380. Epub 2020 Sep 14.

Key Laboratory of Intelligent Control and Decision of Complex Systems, School of Automation, Beijing Institute of Technology, Beijing 100081, China; Key Laboratory of Servo Motion System Drive and Control, Ministry of Industry and Information Technology, School of Automation, Beijing Institute of Technology, Beijing 100081, China.

This paper provides a legged stable walking control strategy based on multi-sensor information feedback about BIT-NAZA-II, a large load parallel hexapod wheel-legged robot developing for the problem of vertical contact impact and horizontal sliding of heavy leg robot in complex terrain environments. The BIT-NAZA-II robot has six legs and six wheels, and the wheels are installed on the foot-end. The wheels of each foot-end for the legs of the robot are locked when walking with legs. In order to realize the smooth transition between swing phase and stance phase, the leg motion is divided into different stages for control by state machine switching controller based on event (SMSCE). In the Z-direction, in order to avoid the shaking of the body caused by the contact impact at the moment of contact between the foot-end and the ground during the walking of the robot, an active compliance controller (ACC) based on impedance control (IC) is applied to solve the problem of contact impact. Moreover, in the X-direction, the swing leg retraction (SLR) based on Bezier curve (BC) is introduced to generate the foot-end trajectory of the robot, which solves the slip problem of the heavy leg robot and improves the horizontal stability. Finally, the control strategy of stable walking is respectively verified by the simulations and experiments. The results show that the ACC based on IC can effectively reduce the contact impact between the foot-end and the ground in the Z-direction and improve the stability of body. Besides, the anti-sliding ability is realized after introducing SLR based on BC in the X-direction, and we also verify that stable walking control strategy is effective, which provides a reference value for the stable walking of heavy leg robot in complex terrain.
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http://dx.doi.org/10.1016/j.isatra.2020.08.033DOI Listing
February 2021

Managing a Large-Scale Multiomics Project: A Team Science Case Study in Proteogenomics.

Methods Mol Biol 2021 ;2194:187-221

Department of Molecular Oncology/Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Highly collaborative scientists are often called on to extend their expertise to different types of projects and to expand the scope and scale of projects well beyond their previous experience. For a large-scale project involving "big data" to be successful, several different aspects of the research plan need to be developed and tested, which include but are not limited to the experimental design, sample collection, sample preparation, metadata recording, technical capability, data acquisition, approaches for data analysis, methods for integration of different data types, recruitment of additional expertise as needed to guide the project, and strategies for clear communication throughout the project. To capture this process, we describe an example project in proteogenomics that built on our collective expertise and experience. Key steps included definition of hypotheses, identification of an appropriate clinical cohort, pilot projects to assess feasibility, refinement of experimental designs, and extensive discussions involving the research team throughout the process. The goal of this chapter is to provide the reader with a set of guidelines to support development of other large-scale multiomics projects.
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http://dx.doi.org/10.1007/978-1-0716-0849-4_11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771375PMC
March 2021

The vascular endothelial cell-expressed prion protein doppel promotes angiogenesis and blood-brain barrier development.

Development 2020 09 23;147(18). Epub 2020 Sep 23.

Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA

The central nervous system (CNS) contains a complex network of blood vessels that promote normal tissue development and physiology. Abnormal control of blood vessel morphogenesis and maturation is linked to the pathogenesis of various neurodevelopmental diseases. The CNS-specific genes that regulate blood vessel morphogenesis in development and disease remain largely unknown. Here, we have characterized functions for the gene encoding prion protein 2 () in CNS blood vessel development and physiology. encodes the glycosylphosphatidylinositol (GPI)-linked protein doppel, which is expressed on the surface of angiogenic vascular endothelial cells, but is absent in quiescent endothelial cells of the adult CNS. During CNS vascular development, doppel interacts with receptor tyrosine kinases and activates cytoplasmic signaling pathways involved in endothelial cell survival, metabolism and migration. Analysis of mice genetically null for revealed impaired CNS blood vessel morphogenesis and associated endothelial cell sprouting defects. mice also displayed defects in endothelial barrier integrity. Collectively, these data reveal novel mechanisms underlying doppel control of angiogenesis in the developing CNS, and may provide new insights about dysfunctional pathways that cause vascular-related CNS disorders.
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http://dx.doi.org/10.1242/dev.193094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522017PMC
September 2020

The efficacy of intraoperative ICG fluorescence angiography on anastomotic leak after resection for colorectal cancer: a meta-analysis.

Int J Colorectal Dis 2021 Jan 4;36(1):27-39. Epub 2020 Sep 4.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang, Fuzhou, Fujian, 350004, People's Republic of China.

Objective: The purpose of this study was to investigate whether intraoperative indocyanine green fluorescence angiography can reduce the incidence of anastomotic leak.

Methods: Present authors conducted a systematic search of PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), prospective nonrandomized trials, and retrospective trials up to March 2020. Eleven papers fulfilling the screening criteria were included.

Intervention: Indocyanine green was injected intravenously after the division of the mesentery and colon but before anastomosis. The primary outcome measure was AL rate with at least 3 months of follow-up. Secondary outcome measure was operation time, postoperative complications, surgical site infection, reoperation, and ileus rate. The results were analyzed using STATA 12.0 software (Stata Corp, College Station, TX, USA).

Result: A total of 3137 patients were collected in 11 studies. Meta-analysis showed that compared with conventional surgery, the ICG fluorescence angiography resulted in a fewer AL rate (OR = 0.31; 95% CI 0.21 to 0.44; P < 0.0001), postoperative complications (OR = 0.70; 95% CI 0.51 to 0.96; P < 0.025), and reoperation rate (OR = 0.334; 95% CI 0.16 to 0.68; P = 0.003). Operation time (weighted mean difference - 25.162 min; 95% CI - 58.7 to 8.375; P = 0.141), surgical site infection rate (OR = 1.11; 95% CI 0.59 to 2.09; P = 0.742) did not differ between the two groups.

Conclusion: The result revealed that indocyanine green was associated with a lower anastomotic leakage rate after colorectal cancer resection. However, larger, multicentered, high-quality randomized controlled trials are needed to confirm the benefit of indocyanine green fluorescence angiography.
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http://dx.doi.org/10.1007/s00384-020-03729-1DOI Listing
January 2021

Meta-analysis of natural orifice specimen extraction versus conventional laparoscopy for colorectal cancer.

Langenbecks Arch Surg 2021 Mar 2;406(2):283-299. Epub 2020 Sep 2.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang, Fuzhou, Fujian, 350004, People's Republic of China.

Objective: To compare natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic (LAP) surgery in treating colorectal cancer.

Methods: The present authors conducted a systematic search in the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), prospective nonrandomized studies, and retrospective studies up to May 2019. We used postoperative complications as the main endpoints, and used hospital stay, time to first flatus, operative time, postoperative pain, cosmetic result, wound infections, and oncological outcomes as the secondary endpoints. Subgroup analyses were conducted according to the different specimen extraction sites (transanal and transvaginal). A sensitivity analysis was carried out to evaluate the reliability of the outcomes. RevMan5.3 software was used for statistical analysis.

Result: Twelve studies (one RCT, ten retrospective studies, and one prospective nonrandomized study) involving a total of 1437 patients (NOSES group 665 patients and LAP surgery group 772 patients) were included. Meta-analysis showed that compared with LAP surgery, NOSES resulted in a shorter hospital stay (WMD = -0.79 days; 95% CI -1.17 to -0.42; P < 0.001; P = 0.02), a shorter time to first flatus (WMD = -0.58 days; 95% CI -0.75 to -0.40; P < 0.001), less postoperative pain (WMD = -1.51; 95% CI -1.99 to -1.04; P < 0.001), a better cosmetic result (WMD = 1.37; 95% CI 0.59 to 2.14; P < 0.001), and fewer wound infections (OR = 0.13; 95% CI 0.05 to 0.35; P < 0.001) and postoperative complications (OR = 0.48; 95% CI 0.36 to 0.65; P < 0.001). Oncological outcomes did not differ between the two groups, while the operative time (WMD = 13.95 min; 95% CI 4.55 to 23.35; P = 0.004) was longer in the NOSES group.

Conclusion: The present systematic meta-analysis is an attempt to assess the impact of NOSES, namely, its oncological outcomes and surgical safety in colorectal cancer patients. Pooled comparisons revealed that NOSES was superior to LAP surgery in terms of postoperative morbidity, postoperative pain, hospital stay, the time to first flatus, cosmetic results, and wound infections; however, NOSES was associated with a longer operative time. Considering the abovementioned limitations and the very low level of evidence of the comparisons, further RCTs are required to verify the results of our study.
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http://dx.doi.org/10.1007/s00423-020-01934-8DOI Listing
March 2021