Publications by authors named "Jian Gu"

445 Publications

Synergizing metal-support interactions and spatial confinement boosts dynamics of atomic nickel for hydrogenations.

Nat Nanotechnol 2021 Jul 26. Epub 2021 Jul 26.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Chemical Physics, Key Laboratory of Surface and Interface Chemistry and Energy Catalysis of Anhui Higher Education Institutes, CAS Center for Excellence in Nanoscience, University of Science and Technology of China, Hefei, China.

Atomically dispersed metal catalysts maximize atom efficiency and display unique catalytic properties compared with regular metal nanoparticles. However, achieving high reactivity while preserving high stability at appreciable loadings remains challenging. Here we solve the challenge by synergizing metal-support interactions and spatial confinement, which enables the fabrication of highly loaded atomic nickel (3.1 wt%) along with dense atomic copper grippers (8.1 wt%) on a graphitic carbon nitride support. For the semi-hydrogenation of acetylene in excess ethylene, the fabricated catalyst shows extraordinary catalytic performance in terms of activity, selectivity and stability-far superior to supported atomic nickel alone in the absence of a synergizing effect. Comprehensive characterization and theoretical calculations reveal that the active nickel site confined in two stable hydroxylated copper grippers dynamically changes by breaking the interfacial nickel-support bonds on reactant adsorption and making these bonds on product desorption. Such a dynamic effect confers high catalytic performance, providing an avenue to rationally design efficient, stable and highly loaded, yet atomically dispersed, catalysts.
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http://dx.doi.org/10.1038/s41565-021-00951-yDOI Listing
July 2021

Associations of genetically predicted circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 with bladder cancer risk.

Mol Carcinog 2021 Jul 22. Epub 2021 Jul 22.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Insulin-like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF-1 and IGFBP-3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF-1 and IGFBP-3 using 413 genome-wide association study-identified single nucleotide polymorphisms (SNPs) associated with IGF-1 and four SNPs with IGFBP-3, respectively. We found that higher GRS for IGF-1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54-0.82, p < 0.001). We then used a summary statistics-based MR method, inverse-variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54-0.83, p < 0.001). When we categorized individuals into high and low IGF-1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70-0.89) compared to the low GRS group. Genetically predicted circulating IGFBP-3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF-1 level and bladder cancer risk.
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http://dx.doi.org/10.1002/mc.23334DOI Listing
July 2021

Visualizing Material Processing via Photoexcitation-Controlled Organic-Phase Aggregation-Induced Emission.

Research (Wash D C) 2021 7;2021:9862093. Epub 2021 Jun 7.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.

Aggregation-induced emission (AIE) has been much employed for visualizing material aggregation and self-assembly. However, water is generally required for the preparation of the AIE aggregates, the operation of which limits numerous material processing behaviors. Employing hexathiobenzene-based small molecules, monopolymers, and block copolymers as different material prototypes, we herein achieve AIE in pure organic phases by applying a nonequilibrium strategy, photoexcitation-controlled aggregation. This strategy enabled a dynamic change of molecular conformation rather than chemical structure upon irradiation, leading to a continuous aggregation-dependent luminescent enhancement (up to ~200-fold increase of the luminescent quantum yield) in organic solvents. Accompanied by the materialization of the nonequilibrium strategy, photoconvertible self-assemblies with a steady-state characteristic can be achieved upon organic solvent processing. The visual monitoring with the luminescence change covered the whole solution-to-film transition, as well as the in situ photoprocessing of the solid-state materials.
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http://dx.doi.org/10.34133/2021/9862093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208088PMC
June 2021

Perspectives on Immunotherapy of Metastatic Colorectal Cancer.

Front Oncol 2021 9;11:659964. Epub 2021 Jun 9.

Hepatobiliary/Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.
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http://dx.doi.org/10.3389/fonc.2021.659964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219967PMC
June 2021

Identification of a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma: A case report.

Medicine (Baltimore) 2021 May;100(19):e25957

Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing.

Rationale: Gallbladder carcinoma is a malignant biliary tract tumor which is characterized by poor prognosis. Recent advances in genomic medicine have identified a few novel germline mutations that contribute to the increased risk of gallbladder carcinoma. RAD52 is a crucial human deoxyribonucleic acid (DNA) repair gene involved in maintaining genomic stability and preventing tumor occurrence.

Patient Concerns: A 57-year-old man was hospitalized for space-occupying lesions in the gallbladder.

Diagnosis: A diagnosis of gallbladder adenocarcinoma was made based on computed tomography, B-ultrasound, blood tests, and postoperative pathology.

Interventions: Next-generation sequencing using a 599-gene panel and Sanger sequencing were performed to validate the mutation in the proband and his family members, respectively.

Outcomes: A novel potentially pathogenic heterozygous germline RAD52 missense mutation (c.276T > A: p.N92K) was identified in the patient. Sanger sequencing revealed that this variation was not observed in unaffected family members.

Lessons: We identified a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma. Our results added to the current body of knowledge. It also provides new insights into genetic counseling and targeted therapeutic strategies for patients with gallbladder carcinoma.
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http://dx.doi.org/10.1097/MD.0000000000025957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133115PMC
May 2021

Clinical and Basic Research Progress on Treg-Induced Immune Tolerance in Liver Transplantation.

Front Immunol 2021 20;12:535012. Epub 2021 May 20.

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

Rejection after organ transplantation is a cause of graft failure. Effectively reducing rejection and inducing tolerance is a challenge in the field of transplantation immunology. The liver, as an immunologically privileged organ, has high rates of spontaneous and operational tolerance after transplantation, allowing it to maintain its normal function for long periods. Although modern immunosuppression regimens have serious toxicity and side effects, it is very risky to discontinue immunosuppression regimens blindly. A more effective treatment to induce immune tolerance is the most sought-after goal in transplant medicine. Tregs have been shown to play a pivotal role in the regulation of immune balance, and infusion of Tregs can also effectively prevent rejection and cure autoimmune diseases without significant side effects. Given the immune characteristics of the liver, the correct use of Tregs can more effectively induce the occurrence of operational tolerance for liver transplants than for other organ transplants. This review mainly summarizes the latest research advances regarding the characteristics of the hepatic immune microenvironment, operational tolerance, Treg generation , and the application of Tregs in liver transplantation. It is hoped that this review will provide a deeper understanding of Tregs as the most effective treatment to induce and maintain operational tolerance after liver transplantation.
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http://dx.doi.org/10.3389/fimmu.2021.535012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173171PMC
June 2021

Integration of circulating tumor cell and neutrophil-lymphocyte ratio to identify high-risk metastatic castration-resistant prostate cancer patients.

BMC Cancer 2021 Jun 2;21(1):655. Epub 2021 Jun 2.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Background: The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). However, no study has examined the prognostic value of NLR and PLR in the context of CTCs.

Methods: Baseline CTCs from mCRPC patients were enumerated using the CellSearch System. Baseline NLR and PLR values were calculated using the data from routine complete blood counts. The associations of CTC, NLR, and PLR values, individually and jointly, with progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis, as well as univariate and multivariate Cox models.

Results: CTCs were detected in 37 (58.7%) of 63 mCRPC patients, and among them, 16 (25.4%) had ≥5 CTCs. The presence of CTCs was significantly associated with a 4.02-fold increased risk for progression and a 3.72-fold increased risk of death during a median follow-up of 17.6 months. OS was shorter among patients with high levels of NLR or PLR than those with low levels (log-rank P = 0.023 and 0.077). Neither NLR nor PLR was individually associated with PFS. Among the 37 patients with detectable CTCs, those with a high NLR had significantly shorter OS (log-rank P = 0.024); however, among the 26 patients without CTCs, the OS difference between high- and low-NLR groups was not statistically significant. Compared to the patients with CTCs and low NLR, those with CTCs and high levels of NLR had a 3.79-fold risk of death (P = 0.036). This association remained significant after adjusting for covariates (P = 0.031). Combination analyses of CTC and PLR did not yield significant results.

Conclusion: Among patients with detectable CTCs, the use of NLR could further classify patients into different risk groups, suggesting a complementary role for NLR in CTC-based prognostic stratification in mCRPC.
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http://dx.doi.org/10.1186/s12885-021-08405-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170812PMC
June 2021

Hypoxia Engineered Bone Marrow Mesenchymal Stem Cells Targeting System with Tumor Microenvironment Regulation for Enhanced Chemotherapy of Breast Cancer.

Biomedicines 2021 May 19;9(5). Epub 2021 May 19.

School of Pharmacy, Southwest University for Nationalities, Chengdu 610051, China.

Improving the tumor targeting of docetaxel (DTX) would not only be favored for the chemotherapeutic efficacy, but also reduce its side effects. However, the regulation of the tumor microenvironment could further inhibit the growth of tumors. In this study, we introduced a system consisting of hypoxia-engineered bone marrow mesenchymal stem cells (H-bMSCs) and DTX micelles (DTX-M) for breast cancer treatment. First, the stem cell chemotherapy complex system ([email protected]) with tumor-targeting ability was constructed according to the uptake of DTX-M by hypoxia-induced bMSCs (H-bMSCs). DTX micellization improved the uptake efficiency of DTX by H-bMSCs, which equipped [email protected] with satisfactory drug loading and stability. Furthermore, the migration of [email protected] revealed that it could effectively target the tumor site and facilitate the drug transport between cells. Moreover, in vitro and in vivo pharmacodynamics of [email protected] exhibited a superior antitumor effect, which could promote the apoptosis of 4T1 cells and upregulate the expression of inflammatory factors at the tumor site. In brief, [email protected] enhanced the chemotherapeutic effect in breast cancer treatment.
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http://dx.doi.org/10.3390/biomedicines9050575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160638PMC
May 2021

A retrospective analysis of 12,400 SARS-CoV-2 RNA tests in patients with COVID-19 in Wuhan.

Medicine (Baltimore) 2021 May;100(20):e25916

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan.

Abstract: The outbreak and widely spread of coronavirus disease 2019 (COVID-19) has become a global public health concern. COVID-19 has caused an unprecedented and profound impact on the whole world, and the prevention and control of COVID-19 is a global public health challenge remains to be solved. The retrospective analysis of the large scale tests of SARS-CoV-2 RNA may indicate some important information of this pandemic. We selected 12400 SARS-CoV-2 tests detected in Wuhan in the first semester of 2020 and made a systematic analysis of them, in order to find some beneficial clue for the consistent prevention and control of COVID-19.SARS-CoV-2 RNA was detected in suspected COVID-19 patients with real-time fluorescence quantitative PCR (RT-qPCR). The patients' features including gender, age, type of specimen, source of patients, and the dynamic changes of the clinical symptoms were recorded and statistically analyzed. Quantitative and qualitive statistical analysis were carried out after laboratory detection.The positive rate of SARS-CoV-2 was 33.02% in 12,400 suspected patients' specimens in Wuhan at the first months of COVID-19 epidemics. SARS-CoV-2 RT-qPCR test of nasopharyngeal swabs might produce 4.79% (594/12400) presumptive results. The positive rate of SARS-CoV-2 RNA was significantly different between gender, age, type of specimen, source of patients, respectively (P < .05). The median window period from the occurrence of clinical symptom or close contact with COVID-19 patient to the first detection of positive PCR was 2 days (interquartile range, 1-4 days). The median interval time from the first SARS-CoV-2 positive to the turning negative was 14 days (interquartile range, 8-19.25 days).This study reveals the comprehensive characteristics of the SARS-CoV-2 RNA detection from multiple perspectives, and it provides important clues and may also supply useful suggestions for future work of the prevention and treatment of COVID-19.
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http://dx.doi.org/10.1097/MD.0000000000025916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137137PMC
May 2021

Transportation container for pre-processing cytogenetic assays in radiation accidents.

Sci Rep 2021 May 17;11(1):10398. Epub 2021 May 17.

Center for Applied NanoBioscience and Medicine, Department of Basic Medical Sciences, The University of Arizona, College of Medicine, Phoenix, AZ, 85004, USA.

We report a shipping container that enables a disruptive logistics for cytogenetic biodosimetry for radiation countermeasures through pre-processing cell culture during transportation. The container showed precise temperature control (< 0.01 °C) with uniform sample temperature (< 0.1 °C) to meet the biodosimetry assay requirements. Using an existing insulated shipping box and long shelf life alkaline batteries makes it ideal for national stockpile. Dose curve of cytogenetic biodosimetry assay using the shipping container showed clear dose response and high linear correlation with the control dose curve using a laboratory incubator (Pearson's correlation coefficient: 0.992). The container's ability of pre-processing biological samples during transportation could have a significant impact on radiation countermeasure, as well as potential impacts in other applications such as biobanking, novel molecular or cell-based assays or therapies.
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http://dx.doi.org/10.1038/s41598-021-89832-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129553PMC
May 2021

Critical Comparison between Large and Mini Vertical Flow Immunoassay Platforms for Detection.

Anal Chem 2021 07 14;93(27):9337-9344. Epub 2021 May 14.

Center for Applied NanoBioscience and Medicine, College of Medicine, University of Arizona, Phoenix, Arizona 85004, United States.

is a Gram-negative bacterium that is the causative agent of plague and is widely recognized as a potential biological weapon. Due to the high fatality rate of plague when diagnosis is delayed, the development of rapid, sensitive, specific, and cost-effective methods is needed for its diagnosis. The low calcium response V (LcrV) protein has been identified as a potential microbial biomarker for the diagnosis of plague. In this paper, we present a highly sensitive, paper-based, vertical flow immunoassay (VFI) prototype for the detection of LcrV and the diagnosis of plague. An antigen-capture assay using monoclonal antibodies is employed to capture and detect the LcrV protein, using a colorimetric approach. In addition, the effect of miniaturizing the VFI device is explored based on two different sizes of VFI platforms, denoted as "large VFI" and "mini VFI." Also, a comparative analysis is performed between the VFI platform and a lateral flow immunoassay (LFI) platform to exhibit the improved assay sensitivity suitable for point-of-care (POC) diagnostics. The analytical sensitivity or limit of detection (LOD) in the mini VFI is approximately 0.025 ng/mL, that is, 10 times better than that of the large VFI platform or 80 times over a standard lateral flow configuration. The low LOD of the LcrV VFI appears to be highly suitable for testing clinical samples and potentially diagnosing plague at earlier time points. In addition, optimization of the gold nanoparticle (AuNP) concentration, nanomaterial plasmonic properties, and flow velocity analysis could improve the performance of the VFI. Furthermore, we developed automated image analysis software that shows potential for integrating the diagnostic system into a smartphone. These methods and findings demonstrate that the VFI platform is a highly sensitive device for detecting the LcrV and potentially many other biomarkers.
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http://dx.doi.org/10.1021/acs.analchem.0c05278DOI Listing
July 2021

CHI3L1 alleviate acute liver injury by inhibiting Th1 cells differentiation through STAT3 signaling pathway.

Ann Transl Med 2021 Apr;9(7):529

Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Background: Acute liver injury (ALI) is a severe liver disease. Chitinase 3-like-1 (CHI3L1), a protein belonging to the glycosyl hydrolase family 18, is involved in many diseases, such as inflammatory diseases, bacterial infections, and various malignant tumors; however, the function of CHI3L1 in ALI remains unclear. The objective of this study was to evaluate the protective functions of CHI3L1 against thioacetamide (TAA)-induced ALI in mice and explore its potential mechanisms.

Methods: Data from 20 patients with ALI and 10 healthy subjects was collected. Serum CHI3L1, serum aspartate transaminase (AST), and serum alanine aminotransferase (ALT) were measured. To establish ALI mouse models, thioacetamide was intraperitoneally injected into groups of the CHI3L1-knockout (CHI3L1-KO) and wild-type (WT) mice (80 and 150 mg/kg). Recombinant CHI3L1 protein (rCHI3L1) (5 µg/kg), IFN-γ (500 ng), and WP1033 (an inhibitor of P-STAT3, 0.2 mL) were injected before TAA treatment, after which the effects were estimated. Splenic CD4+CD62L+ naive T cells were isolated from CHI3L1-KO mice and stimulated to differentiate into regulatory T (Treg) cells, T-helper 1 (Th1) cells, T-helper 2 (Th2) cells, and T-helper 17 (Th17) cells.

Results: Increased serum CHI3L1 levels were seen both in healthy subjects and post-therapy patients compared with ALI patients. CHI3L1 levels were negatively correlated with serum ALT and AST levels in ALI patients. CHI3L1-KO group showed higher serum ALT and AST levels than the WT group following TAA treatment, while tail vein injection of rCHI3L1 reduced liver tissue injury and improved Treg cell differentiation . experiment showed that knockout of CHI3L1 improved IFN-γ+ Th1 cell differentiation. Furthermore, intraperitoneal administration of IFN-γ produced more severe hepatocellular necrosis compared with rCHI3L1 injection alone. Mechanism study showed that T-box expressed in T cells (T-bet), and signal transducer and activator of transcription 3 (STAT3), play a critical role in adversely mediating the effect of CHI3L1, which is consistent with the finding that treatment with WP1033 down-regulated the differentiation of the Th1 cells and reduced severity of liver injury .

Conclusions: CHI3L1 reduced the production of IFN-γ and inhibited Th1 cell differentiation through the STAT3 signaling pathway, which could be a potential therapeutic strategy for treating ALI.
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http://dx.doi.org/10.21037/atm-20-6127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105831PMC
April 2021

The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer.

Front Pharmacol 2021 15;12:651976. Epub 2021 Apr 15.

College of Pharmacy, Southwest Minzu University, Chengdu, China.

Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast cancer treatment. In the present study, we evaluated the activities of a novel Stat3 inhibitor named Statmp-151 in the human breast cancer cell lines MCF-7 and MDA-MB-231 and the murine mammary carcinoma cell line 4T1. The results showed that Statmp-151 inhibited the proliferation of breast cancer cell lines in a dose- and time-dependent manner and suppressed the phosphorylation of Stat3 in a dose-dependent manner. Flow cytometry (FCM) assays revealed that Statmp-151 affected mitochondrial membrane potential and reactive oxygen species (ROS) production. Furthermore, Statmp-151 inhibited cell migration, as shown by analysis of the matrix metalloproteinases MMP2 and MMP9. Finally, in a 4T1 tumour-bearing mouse model, intraperitoneal injection of 30 mg/kg/day Statmp-151 significantly suppressed the growth of tumours without obvious toxicity. These results indicated that Statmp-151 might be a potential candidate for the treatment of breast cancer.
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http://dx.doi.org/10.3389/fphar.2021.651976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099110PMC
April 2021

Identification of Mitochondrial-Related Prognostic Biomarkers Associated With Primary Bile Acid Biosynthesis and Tumor Microenvironment of Hepatocellular Carcinoma.

Front Oncol 2021 1;11:587479. Epub 2021 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-associated deaths worldwide. Despite great progress in early diagnosis and multidisciplinary tumor management, the long-term prognosis of HCC remains poor. Currently, metabolic reprogramming during tumor development is widely observed to support rapid growth and proliferation of cancer cells, and several metabolic targets that could be used as cancer biomarkers have been identified. The liver and mitochondria are the two centers of human metabolism at the whole organism and cellular levels, respectively. Thus, identification of prognostic biomarkers based on mitochondrial-related genes (Mito-RGs)-the coding-genes of proteins located in the mitochondria-that reflect metabolic changes associated with HCC could lead to better interventions for HCC patients. In the present study, we used HCC data from The Cancer Genome Atlas (TCGA) database to construct a classifier containing 10 Mito-RGs (ACOT7, ADPRHL2, ATAD3A, BSG, FAM72A, PDK3, PDSS1, RAD51C, TOMM34, and TRMU) for predicting the prognosis of HCC by using 10-fold Least Absolute Shrinkage and Selection Operation (LASSO) cross-validation Cox regression. Based on the risk score calculated by the classifier, the samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), t-distributed stochastic neighbor embedding (t-SNE), and consensus clusterPlus algorithms were used to identify metabolic pathways that were significantly different between the high- and low-risk groups. We further investigated the relationship between metabolic status and infiltration of immune cells into HCC tumor samples by using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm combined with the Tumor Immune Estimation Resource (TIMER) database. Our results showed that the classifier based on Mito-RGs could act as an independent biomarker for predicting survival of HCC patients. Repression of primary bile acid biosynthesis plays a vital role in the development and poor prognosis of HCC, which provides a potential approach to treatment. Our study revealed cross-talk between bile acid and infiltration of tumors by immune cells, which may provide novel insight into immunotherapy of HCC. Furthermore, our research may provide a novel method for HCC metabolic therapy based on modulation of mitochondrial function.
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http://dx.doi.org/10.3389/fonc.2021.587479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047479PMC
April 2021

High circulating insulin-like growth factor-1 reduces the risk of renal cell carcinoma: a Mendelian randomization study.

Carcinogenesis 2021 Jun;42(6):826-830

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Insulin and insulin-like growth factors play important roles in carcinogenesis. Circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have been linked to cancer susceptibility. The associations of circulating IGF-1 and IGFBP-3 with the risk of renal cell carcinoma (RCC) are inconsistent. Recent large genome-wide association studies have identified 413 single nucleotide polymorphisms (SNPs) associated with IGF-1 and 4 SNPs associated with IGFBP-3. In this large case-control study consisting of 2069 RCC patients and 2052 healthy controls of European ancestry, we used a two-sample Mendelian randomization (MR) approach to investigate the associations of genetically predicted circulating IGF-1 and IGFBP-3 with RCC risk. We used an individual level data-based genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses. We found that genetically predicted IGF-1 was significantly associated with RCC risk in both the GRS analysis [odds ratio (OR) = 0.43 per SD increase, 95% confidence interval (CI), 0.34-0.53] and the IVW analysis (OR = 0.46 per SD increase, 95% CI, 0.37-0.57). Dichotomized at the median GRS value of IGF-1 in controls, individuals with high GRS had a 45% reduced RCC risk (OR = 0.55, 95% CI, 0.48-0.62) compared with those with low GRS. Genetically predicted circulating IGFBP-3 was not associated with RCC risk. This is the largest RCC study of circulating IGF-1 and IGFBP-3 to date and our data suggest a strong inverse relationship between circulating IGF-1 level and RCC risk.
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http://dx.doi.org/10.1093/carcin/bgab031DOI Listing
June 2021

Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs.

Front Cell Dev Biol 2021 25;9:637248. Epub 2021 Mar 25.

Department of Neonatology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.
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http://dx.doi.org/10.3389/fcell.2021.637248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027316PMC
March 2021

Genome-wide DNA methylation profiling of leukocytes identifies CpG methylation signatures of aggressive prostate cancer.

Am J Cancer Res 2021 1;11(3):968-978. Epub 2021 Mar 1.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center Houston, TX 77030, USA.

Most of screening-detected prostate cancer (PCa) are indolent and not lethal. Biomarkers that can predict aggressive diseases independently of clinical features are needed to improve risk stratification of localized PCa patients and reduce overtreatment. We aimed to identify leukocyte DNA methylation differences between clinically defined aggressive and non-aggressive PCa. We performed whole genome DNA methylation profiling in leukocyte DNA from 287 PCa patients with Gleason Score (GS) 6 and ≥8 using Illumina 450k methylation arrays. We observed a global hypomethylation in GS≥8 patients compared to GS=6 PCa patients; in contrast, the methylation level in core promoter and exon 1 region was significantly higher in GS≥8 patients than GS=6 PCa. We then performed 5-fold cross validated random forest model training on 1,459 differentially methylated CpG Probes (DMPs) with false discovery rate (FDR) <0.01 between GS=6 and GS≥8 groups. The power of the predictive model was further reinforced by ranking the DMPs with Decreased Gini and re-train the model with the top 97 DMPs (Testing AUC=0.920, predict accuracy =0.847). In conclusion, we identified a CpG methylation signature in leukocyte DNA that is associated with aggressive clinical features of PCa at diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994169PMC
March 2021

Alpha-Lipoic Acid Attenuates Cadmium- and Lead-Induced Neurotoxicity by Inhibiting Both Endoplasmic-Reticulum Stress and Activation of Fas/FasL and Mitochondrial Apoptotic Pathways in Rat Cerebral Cortex.

Neurotox Res 2021 Aug 10;39(4):1103-1115. Epub 2021 Mar 10.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

Although many studies have reported toxic effects of cadmium (Cd) and lead (Pb) in the central nervous system, few studies have investigated the combined toxicity of Cd and Pb. The mechanisms by which these combined heavy metals induce toxicity, as well as effective means to exert neuroprotection from these agents, remain poorly understood. To investigate the protective effects of alpha-lipoic acid (α-LA) on Cd- and/or Pb-induced cortical damage in rats, 48 Sprague-Dawley rats were exposed to drinking water containing 50 mg/L of Cd and/or 300 mg/L of Pb for 12 weeks, in the presence or absence of α-LA co-treatment (50 mg/kg) via gavage. We observed that exposure to Cd and/or Pb decreased the brain weight/body weight ratio and increased Cd and/or Pb contents as well as ultrastructural damage to the cerebral cortex. Cd and/or Pb also induced endoplasmic-reticulum (ER) stress and activated Fas (CD95/APO-1)/Fas ligand (FasL) and mitochondrial apoptotic pathways. Furthermore, co-treatment of Cd and Pb further exacerbated part of these phenotypes than treatment of Cd or Pb alone. However, simultaneous supplementation with α-LA attenuated Cd and/or Pb-induced neurotoxicity by increasing the brain weight/body weight ratio, reducing Cd and/or Pb contents, ameliorating both nuclear/mitochondrial damage and ER stress, and attenuating activation of Fas/FasL and mitochondrial apoptotic pathways. Collectively, our results indicate that the accumulation of Cd and/or Pb causes cortical damage and that α-LA exerts protection against Cd- and/or Pb-induced neurotoxicity. These findings highlight that α-LA may be exploited for the treatment and prevention of Cd- and/or Pb-induced neurotoxicity.
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http://dx.doi.org/10.1007/s12640-021-00348-8DOI Listing
August 2021

The Role of Dyslipidemia in Colitis-Associated Colorectal Cancer.

J Oncol 2021 12;2021:6640384. Epub 2021 Feb 12.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Dyslipidemia, characterized by metabolic abnormalities, has become an important participant in colorectal cancer (CRC). Dyslipidemia aggravates intestinal inflammation, destroys the protective mucous layer, and disrupts the balance between injury and recovery. On the other hand, antioxidants induced by oxidative stress enhance glycolysis to maintain the acquisition of ATP allowing epithelial cells with damaged genomes to survive. In the repetitive phase of colitis, survival factors enable these epithelial cells to continuously proliferate. The main purpose is to restore and rebuild damaged mucosa, mainly aiming to recover mucosal damage and reconstruct mucosa, but it is also implicated in the occurrence and malignancy of CRC. The metabolic reprogramming of aerobic glycolysis and lipid synthesis enables these transformed epithelial cells to convert raw carbohydrate and amino acid substrates, thereby synthesizing protein and phospholipid biomass. Stearoyl-CoA desaturase, responsible for the fatty acid desaturation, improves the fluidity and permeability of cell membranes, which is one of the key factors affecting metabolic rate. In response to available fat, tumor cells reprogram their metabolism to better plunder energy-rich lipids and rapidly scavenge these lipids through continuous proliferation. However, lipid metabolic disorders inhibit the function of immune-infiltrating cells in the tumor microenvironment through the cross-talk between tumor cells and immunosuppressive stromal cells, thereby providing opportunities for tumor progress. Nonsteroidal anti-inflammatory drugs and lipid-lowering drugs can decrease the formation of aberrant crypt foci, lower the burden of the adenomatous polyp, and reduce the incidence of CRC. This review provides a comprehensive understanding of dyslipidemia on tumorigenesis and tumor progression and a development prospect of lipid disorders on tumor immunity.
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http://dx.doi.org/10.1155/2021/6640384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895570PMC
February 2021

Improved Prognostic Stratification Using Circulating Tumor Cell Clusters in Patients with Metastatic Castration-Resistant Prostate Cancer.

Cancers (Basel) 2021 Jan 13;13(2). Epub 2021 Jan 13.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Liquid biopsy-based biomarkers have advantages in monitoring the dynamics of metastatic castration-resistant prostate cancer (mCRPC), a bone-predominant metastatic disease. Previous studies have demonstrated associations between circulating tumor cells (CTCs) and clinical outcomes of mCRPC patients, but little is known about the prognostic value of CTC-clusters. In 227 longitudinally collected blood samples from 64 mCRPC patients, CTCs and CTC-clusters were enumerated using the CellSearch platform. The associations of CTC and CTC-cluster counts with progression-free survival (PFS) and overall survival (OS), individually and jointly, were evaluated by Cox models. CTCs and CTC-clusters were detected in 24 (37.5%) and 8 (12.5%) of 64 baseline samples, and in 119 (52.4%) and 27 (11.9%) of 227 longitudinal samples, respectively. CTC counts were associated with both PFS and OS, but CTC-clusters were only independently associated with an increased risk of death. Among patients with unfavorable CTCs (≥5), the presence of CTC-clusters signified a worse survival (log-rank = 0.0185). mCRPC patients with both unfavorable CTCs and CTC-clusters had the highest risk for death (adjusted hazard ratio 19.84, = 0.0072), as compared to those with <5 CTCs. Analyses using longitudinal data yielded similar results. In conclusion, CTC-clusters provided additional prognostic information for further stratifying death risk among patients with unfavorable CTCs.
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http://dx.doi.org/10.3390/cancers13020268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828213PMC
January 2021

Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

Clin Infect Dis 2020 12;71(Suppl 4):S363-S371

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015.

Methods: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System.

Results: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions.

Conclusions: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.
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http://dx.doi.org/10.1093/cid/ciaa1536DOI Listing
December 2020

High-accuracy optical extensometer realized by two parallel cameras and two-dimensional digital image correlation.

Appl Opt 2020 Dec;59(34):10813-10825

A conventional optical extensometer realized by a single common camera and two-dimensional digital image correlation (2D-DIC) often provides unsatisfactory strain results owing to the out-of-plane motion of the specimen. In this work, we propose an improved optical extensometer based on two parallel cameras and 2D-DIC. In the proposed extensometer, the gauge points are selected at the image centers of two cameras, which are negligibly affected by the out-of-plane translation and rotation, leading to higher accuracy of strain measurement as compared with the conventional optical extensometer. A rigid out-of-plane translation experiment and four repeated uniaxial tensile tests were conducted to verify the feasibility, reliability, and accuracy of the proposed method. Experimental results indicate that the proposed method has a strong ability to resist the effect of out-of-plane motion and experimental vibrations. Moreover, the strain measurement results obtained with the proposed method were found to be in excellent agreement with those obtained with a strain gauge, and the strain errors between them were only a few microstrains. Given that no compensation method is required, the proposed method is easy to implement with 2D-DIC and can be used for specimens of different sizes by adjusting the distance between the two cameras.
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http://dx.doi.org/10.1364/AO.405419DOI Listing
December 2020

[Study on protective mechanism of Tibetan medicine Ershiwuwei Songshi Pills on cholestatic liver injury in rats based on FXR signaling pathway].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(21):5273-5279

College of Pharmacy, Southwest Minzu University Chengdu 610041, China.

This paper aimed to investigate the protective effect and mechanism of the Tibetan medicine Ershiwuwei Songshi Pills on α-naphthalene isothiocyanate(ANIT)-induced cholestatic liver injury in rats based on the farnesol X receptor(FXR) signaling pathway. SD rats were randomly divided into blank group, model group, ursodeoxycholic acid(UDCA) group, Tibetan medicine Ershiwuwei Songshi Pills low, medium and high dose groups(0.09, 0.18, 0.36 g·kg~(-1)). A prophylactic dosing regimen was used in the experiment. From the 1 st to 4 th days, the UDCA group and the Tibetan medicine Ershiwuwei Songshi Pills suspension groups received prophylactic gavage administration; on the 5 th day, the blank control group was given an equal volume of olive oil blank reagent, and the remaining groups were given ANIT modeling reagent. Administration was continued on day 5 to 6 in each administration group. Forty-eight hours after modeling on the 7 th day, blood was collected from the femoral artery of rats. Serum alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), direct bilirubin(DBIL), total bilirubin(TBIL), and total bile acid(TBA) levels were detected, and liver histopathological changes were observed. The relative expression changes of FXR, SHP, CYP7 A1, MRP2, MRP3, NTCP, BSEP mRNA in liver tissues were detected by Real-time fluorescence quantitative method, and the expression changes of FXR, SHP, UGT2 B4 protein in liver tissues were detected by Western blot. The results showed that the Tibetan medicine Ershiwuwei Songshi Pills significantly reduced the levels of ALT, ALP, DBIL, TBIL and TBA in the serum of the ANIT mo-del rats(P<0.01, P<0.05), significantly up-regulated the mRNA expressions of SHP and NTCP(P<0.01, P<0.05), significantly down-regulated the mRNA expression of CYP7 A1 and MRP3(P<0.01, P<0.05); and significantly up-regulated the protein expressions of FXR and SHP(P<0.01, P<0.05). The Tibetan medicine Ershiwuwei Songshi Pills have an obvious protective effect on ANIT-induced cholestatic liver injury in rats, and its mechanism may be related to the bile acid metabolism mediated by the FXR signaling pathway.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200727.401DOI Listing
November 2020

Inhibition of Glycogen Synthase Kinase 3β Increases the Proportion and Suppressive Function of CD19CD24CD27 Breg Cells.

Front Immunol 2020 4;11:603288. Epub 2020 Dec 4.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

CD19CD24CD27 memory Breg cells exhibit decreased abundance in patients with chronic graft-versus-host disease (cGVHD) after liver transplantation and produce less IL-10 than those from patients without cGVHD and healthy donors. Due to the lack of Breg cells and the difficulty in expanding them , in mouse models and early human clinical trials, the adoptive transfer of Breg cells to autoimmune diseases is greatly restricted. Glycogen synthase kinase 3β (GSK-3β) is a multifunctional serine/threonine (ser/thr) protein kinase that can participate in B cell growth, metabolic activity, and proliferation. Phosphoprotein array analysis showed that p-GSK-3β-s9 was highly expressed in mBreg cells. Furthermore, here, we demonstrated that GSK-3β expression in mBreg cells is lower than that observed in B cells by flow cytometry. We found that the treatment of B cells with the specific GSK-3β inhibitor SB216763 can significantly increase the proportion and immunosuppressive function of mBreg cells . Nuclear factor of activated T cells (NFAT) is one of a pivotal regulator of gene expression in adaptive immune system. Here, we observed that inhibition of GSK-3β by SB216763 results in enhanced expression of NFATc1 in B cells, which is essential in regulating the ability of B cells to secrete IL-10. By constructing a xGVHD mouse model, we observed that SB216763-treated mBreg cells effectively prevent xenogeneic GVHD. Here we propose a novel strategy using SB216763 to inhibit GSK-3β and then enhance the proportion and immunosuppressive function of mBreg cells by increasing the expression of NFATc1. This approach may be used as a therapy to ameliorate GVHD and inflammatory diseases.
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http://dx.doi.org/10.3389/fimmu.2020.603288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746849PMC
June 2021

Green preparation of high-quality and low-cost graphene from discarded polyethylene plastic bags.

Chem Commun (Camb) 2021 Jan;57(1):129-132

Science and Technology on Aerospace Chemical Power Laboratory, Xiangyang 441003, P. R. China.

A facile method was used to prepare graphene from discarded polyethylene plastic bags in our work. In order to make high-quality graphene, PE plastic bags were ultrasonically cleaned, ball milled and microwave sintered successively. The height of the 2D band was 1.3 times that of the G band, which reveals that the layer number of as-prepared graphene was 1-2. The atomic ratio of C and O for graphene was more than 54, which indicates that it mainly consists of carbon. The size of graphene was within 4-10 μm. Bi-layer sheets were inevitably observed through high resolution imaging of graphene edges. The BET SSA and the electrical conductivity of graphene were 1521.3 m2 g-1 and 4618 S m-1, respectively. This work provides a new approach to large-scale and high-quality synthesis of graphene from waste polluting materials.
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http://dx.doi.org/10.1039/d0cc06999jDOI Listing
January 2021

Synthesis of Quasi-Bilayer Subnano Metal-Oxide Interfacial Cluster Catalysts for Advanced Catalysis.

Small 2020 Dec 30;16(52):e2005571. Epub 2020 Nov 30.

Department of Chemical Physics, Key Laboratory of Surface and Interface Chemistry and Energy Catalysis of Anhui Higher Education Institutes, University of Science and Technology of China, Hefei, Anhui, 230026, China.

Planar metal clusters possess high metal utilization, distinct electronic properties, and catalytic functions from their 3D counterparts. However, synthesis of these materials is challenging due to much elevated surface free energies. Here it is reported that silica supported planar bilayer Pt-CoO subnano clusters, consisting of approximately one atomic layer of Pt and one CoO layer on top, can be achieved by employing strong-electrostatic interactions during impregnation and precisely-controlled CoO coating using atomic layer deposition. Such bilayer structure is unambiguously confirmed by electron microscopy and in situ X-ray absorption fine spectroscopy which is never reported before. This synthetic approach can be extended to another eight permutations of planar metal-oxide subnano clusters. The resulting bilayer catalysts, owing to unique electronic properties and the abundant metal-oxide interfaces created, exhibit excellent catalytic performances in the reactions of preferential oxidation of CO in H and selective hydrogenation of acetylene, by showing much higher selectivity and intrinsic activities at least 8 and 48 times greater than those conventional oxide coated 3D metal clusters/nanoparticles, highlighting the advances of bilayer interfacial structure. These findings open a new avenue to design abundant and highly active metal-oxide interfaces for advanced metal catalysis.
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http://dx.doi.org/10.1002/smll.202005571DOI Listing
December 2020

Prognostic value of leukocyte telomere length in renal cell carcinoma patients.

Am J Cancer Res 2020 1;10(10):3428-3439. Epub 2020 Oct 1.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center Houston, TX 77030, USA.

Telomeres play important roles in cancer initiation and progression. Leukocyte telomere length (LTL) can modulate cancer risk and outcome. We hypothesize that genetically predicted short LTL is associated with worse prognosis in renal cell carcinoma (RCC). A total of 1,086 histologically confirmed RCC patients were included in this study. A weighted genetic risk score (GRS) predictive of LTL was constructed using 10 confirmed LTL-associated single nucleotide polymorphisms (SNPs). The associations of individual SNPs and GRS with recurrence and survival were determined by multivariate Cox proportional hazards analysis. In individual SNP analysis, long LTL-associated allele of rs7675998 in NAF1 gene at chromosome 4 was significantly associated with a reduced risk of recurrence (HR=0.85, 95% CI, 0.73-0.99, P=0.043), while the long LTL-associated allele of rs10936599 in TERC at chromosome 3 conferred a reduced risk of death (HR=0.85, 95% CI, 0.73-1.00, P=0.047). More importantly, genetically predicted LTL was associated with both recurrence and survival. Dichotomized at the median value of GRS, patients with low GRS (indicating short LTL) exhibited significantly increased risks of recurrence (HR=1.26, 95% CI, 1.03-1.54, P=0.025) and death (HR=1.23, 95% CI, 1.00-1.50, P=0.045). Hence, we concluded that genetically predicted short LTL is associated with worse prognosis in RCC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642657PMC
October 2020

Indocyanine green fluorescence navigation in laparoscopic hepatectomy: a retrospective single-center study of 120 cases.

Surg Today 2021 May 31;51(5):695-702. Epub 2020 Oct 31.

Hepatobiliary Center, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Purpose: To explore the role of indocyanine green (ICG) fluorescence navigation in laparoscopic hepatectomy and investigate if the timing of its administration influences the intraoperative observation.

Methods: The subjects of this retrospective study were 120 patients who underwent laparoscopic hepatectomy; divided into an ICG-FN group (n = 57) and a non-ICG-FN group (n = 63). We analyzed the baseline data and operative data.

Results: There were no remarkable differences in baseline data such as demographic characteristics, lesion-related characteristics, and liver function parameters between the groups. Operative time and intraoperative blood loss were significantly lower in the ICG-FN group. The rate of R0 resection of malignant tumors was comparable in the ICG-FN and non-ICG-FN groups, but the wide surgical margin rate was significantly higher in the ICG-FN group. The administration of ICG 0-3 or 4-7 days preoperatively did not affect the intraoperative fluorescence imaging. Operative time, intraoperative blood loss, and a wide surgical margin correlated with ICG fluorescence navigation. ICG fluorescence navigation helped to minimize intraoperative blood loss and achieve a wide surgical margin.

Conclusion: ICG fluorescence navigation is safe and efficient in laparoscopic hepatectomy. It helps to achieve a wide surgical margin, which could result in a better prognosis. The administration of ICG 0-3 days preoperatively is acceptable.
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http://dx.doi.org/10.1007/s00595-020-02163-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055570PMC
May 2021

Association between Serum Calcium and First Incident Acute Myocardial Infarction: A Cross-Sectional Study.

Iran J Public Health 2020 Jul;49(7):1278-1288

Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Background: The role of serum calcium in coronary artery disease (CAD) patients with or without first incident acute myocardial infarction has not been studied previously. This study aimed to assess the relationship between serum calcium and first incident acute myocardial infarction.

Methods: This cross-sectional study was conducted from Jan 2014 to Dec 2016. All the participants were from our database, described in detail elsewhere including 1609 cases and 3252 controls. Multiple logistic regression was carried out to explore the effect of serum calcium on first incident acute myocardial infarction. Interaction between serum calcium and risk factors were evaluated.

Results: Patients with first incident acute myocardial infarction have significantly lower serum calcium concentrations than those without acute myocardial infarction (2.18 (0.21) vs 2.24 (0.19) mmol/L, <0.0001). After adjusting for sex and age, logistic regression showed that serum calcium was significantly associated with first incident acute myocardial infarction (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.41-1.60). Further adjusted for potential confounders, serum calcium was associated with first incident acute myocardial infarction (OR: 1.32, 95% CI: 1.22-1.42). Moreover, the association still existed when patients were divided into subgroups according to gender and age. A significant interaction was found between serum calcium and diabetes mellitus (DM), lipoprotein (a) (Lp (a)), and serum albumin.

Conclusion: Serum calcium was associated with first incident acute myocardial infarction among CAD patients in both sexes and in age categories. This study provides further evidence showing the value of serum calcium levels in clinical practice.
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http://dx.doi.org/10.18502/ijph.v49i7.3581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548486PMC
July 2020

Leukocyte Telomere Length and Bladder Cancer Risk: A Large Case-Control Study and Mendelian Randomization Analysis.

Cancer Epidemiol Biomarkers Prev 2021 01 30;30(1):203-209. Epub 2020 Sep 30.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Leukocyte telomere length (LTL) has been associated with risk of several cancers. The association between LTL and bladder cancer is still inconsistent.

Methods: In this large case-control study consisting of 2,011 patients with bladder cancer and 2,259 healthy controls of European ancestry, we investigated the associations of real-time qPCR-measured LTL (a retrospective case-control study) and genetically predicted LTL [a Mendelian randomization (MR) study] with bladder cancer risk. Genotypes from 10 LTL-associated SNPs were used as instrumental variables to predict LTL. We used an individual level data-based weighted genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses.

Results: The qPCR-measured LTL was shorter in cases with muscle-invasive bladder cancer (MIBC) than those with non-muscle-invasive bladder cancer [NMIBC; ratio of telomere repeats copy number to single gene copy number (T/S): 1.19 ± 0.34 vs. 1.23 ± 0.36, = 0.081]. Multivariable logistic regression analyses showed long qPCR-measured LTL was associated with a reduced risk of MIBC. In MR analyses, genetically predicted LTL was weakly associated with bladder cancer risk in both the GRS analysis [OR = 1.13, per SD increase; 95% confidence interval (CI), 0.73-1.75; = 0.595] and the IVW analysis (OR = 1.14 per SD increase; 95% CI, 0.75-1.74; = 0.543).

Conclusions: There was no strong evidence supporting an association between LTL and bladder cancer risk in European Americans.

Impact: This is the largest study of LTL and bladder cancer risk. The study showed that LTL does not play an important role in bladder cancer etiology.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0351DOI Listing
January 2021
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