Publications by authors named "Quan Zhou"

665 Publications

Metastatic and sentinel lymph node mapping using intravenously delivered Panitumumab-IRDye800CW.

Theranostics 2021 24;11(15):7188-7198. Epub 2021 May 24.

Department of Otolaryngology - Division of Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.

Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.
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http://dx.doi.org/10.7150/thno.55389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210603PMC
May 2021

EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial.

Theranostics 2021 21;11(15):7130-7143. Epub 2021 May 21.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. : Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and , to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. : No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. : Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.
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http://dx.doi.org/10.7150/thno.60582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210618PMC
May 2021

MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats.

Front Physiol 2021 1;12:674430. Epub 2021 Jun 1.

Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, China.

A previous study from our team found that hyperbaric oxygen (HBO) pretreatment attenuated decompression sickness (DCS) spinal cord injury by upregulating heat shock protein 32 (HSP32) via the ROS/p38 MAPK pathway. Meanwhile, a MEK1/2-negative regulatory pathway was also activated to inhibit HSP32 overexpression. The purpose of this study was to determine if normobaric oxygen (NBO) might effectively induce HSP32 while concurrently inhibiting MEK1/2 and to observe any protective effects on spinal cord injury in DCS rats. The expression of HSP32 in spinal cord tissue was measured at 6, 12, 18, and 24 h following NBO and MEK1/2 inhibitor U0126 pretreatment. The peak time of HSP32 was observed at 12 h after simulated air diving. Subsequently, signs of DCS, hindlimb motor function, and spinal cord and serum injury biomarkers were recorded. NBO-U0126 pretreatment significantly decreased the incidence of DCS, improved motor function, and attenuated oxidative stress, inflammatory response, and apoptosis in both the spinal cord and serum. These results suggest that pretreatment with NBO and U0126 combined can effectively alleviate DCS spinal cord injury in rats by upregulating HSP32. This may lead to a more convenient approach for DCS injury control, using non-pressurized NBO instead of HBO.
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http://dx.doi.org/10.3389/fphys.2021.674430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204088PMC
June 2021

Expression and Prognostic Value of ARID5A and its Correlation With Tumor-Infiltrating Immune Cells in Glioma.

Front Oncol 2021 19;11:638803. Epub 2021 May 19.

Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, China.

AT-rich interaction domain 5A (ARID5A) is a member of the ARID family with a function that has been linked to autoimmune as well as inflammatory diseases. Some ARID family members are involved in the initiation and progression of human cancers. However, the function of ARID5A in glioma remains unknown. In this study, ARID5A expression levels were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Subsequently, the relationship between ARID5A expression and the clinical characteristics of glioma patients was evaluated using the Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database. The prognostic value of ARID5A in glioma was estimated by Kaplan-Meier analysis and the receiver operating characteristic (ROC) curve analysis. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed for functional prediction. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between ARID5A and immune cell infiltration in glioma. Our results demonstrate that the expression of ARID5A was upregulated in glioma compared with that in nontumor brain tissues. High expression of ARID5A is associated with poor prognosis in glioma. We found that the expression of ARID5A was significantly upregulated with an increase in tumor malignancy. GO analysis revealed that co-expression genes of ARID5A are significantly involved in some important functions in glioma, and GSEA showed that multiple cancer-associated and immune-associated signaling pathways are enriched in the high ARID5A expression group. TIMER database indicated that ARID5A is correlated with tumor-infiltrating immune cells in glioma. Collectively, these findings indicate that ARID5A may be a potential prognostic biomarker and is correlated with immune infiltration in glioma.
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http://dx.doi.org/10.3389/fonc.2021.638803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172138PMC
May 2021

[Responses of root exudates to intercropping of Chinese milk vetch with rape.]

Ying Yong Sheng Tai Xue Bao 2021 May;32(5):1783-1790

Research Center on Ecological Sciences, Jiangxi Agricultural University/Key Laboratory of Crop Physio-logy, Ecology and Genetic Breeding, Ministry of Education, Nanchang 330045, China.

Root exudates are important carriers for material exchange and information transfer between plant and soil, and important regulators of crop-soil-microorganism interaction in intercropping systems. We examined the interaction between crops in intercropping system by setting three treatments, monoculture Chinese milk vetch, monoculture rape and Chinese milk vetch intercropped with rape. The responses of root exudates were emphatically analyzed. The results showed that 391 root exudates were detected, with 93 of which being identified and divided into nine types of metabo-lites. Among them, organooxygen compounds were the most abundant, mainly in the form of ribitol. Under different planting patterns, root exudates of Chinese milk vetch and rape were significantly different. The characteristics of root exudates in intercropping were similar to monoculture rape, but significantly different from monoculture Chinese milk vetch. Among the root exudates in different planting modes, only 9-fluorenone 1 was negatively correlated with others. The differential root exudates were mainly benzenoids, lipids and lipid-like molecules, organic acids and derivatives, and organooxygen compounds. The benzenoids, lipids and lipid-like molecules were important types that characterized the changes of root exudates of Chinese milk vetch and rape. Chinese milk vetch intercropping with rape changed the characteristics of root exudates, which were closely related to benzenoids, lipids, and lipid-like molecules.
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http://dx.doi.org/10.13287/j.1001-9332.202105.024DOI Listing
May 2021

Cough Recognition Based on Mel-Spectrogram and Convolutional Neural Network.

Front Robot AI 2021 7;8:580080. Epub 2021 May 7.

Beijing National Research Center for Information Science and Technology, Department of Computer Science and Technology, Tsinghua University, Beijing, China.

In daily life, there are a variety of complex sound sources. It is important to effectively detect certain sounds in some situations. With the outbreak of COVID-19, it is necessary to distinguish the sound of coughing, to estimate suspected patients in the population. In this paper, we propose a method for cough recognition based on a Mel-spectrogram and a Convolutional Neural Network called the Cough Recognition Network (CRN), which can effectively distinguish cough sounds.
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http://dx.doi.org/10.3389/frobt.2021.580080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138471PMC
May 2021

Hsa_circ_0000301 facilitates the progression of cervical cancer by targeting miR-1228-3p/IRF4 Axis.

BMC Cancer 2021 May 21;21(1):583. Epub 2021 May 21.

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P.R. China.

Background: With the broadened application of gene expression profiles analysis, the role of miRNA and circRNA are of increasing concern in recent years, especially during the pathogenesis of cancer. However, to date, the reported on this area in cervical cancer are limited.

Method: In this study, Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis were utilized to screen out differentially expressed (DE) circular RNAs in cervical cancer, and then we predicted and screened the combined microRNAs (miRNA) and downstream mRNAs to construct circular (circ)RNA-miRNA-mRNA network.

Result: As a result, a regulatory circular (circ)RNA-miRNA-mRNA with 1 circRNA node, 4 miRNA nodes, 135 mRNA nodes were constructed in an attempt to provide novel biomarkers for the pathogenesis of cervical cancer. In addition, enrichment analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on mRNAs in the network. After further screening of mRNAs by two online databases of GEPIA2 and RNAyhrid, precise target genes were obtained. Next, we screened out four target genes (CXCL16, IRF4, OAS3 and PTGER3) by constructing the protein-protein interaction (PPI) network, and mapped them to the initial network to reconstruct the circRNA-miRNA-mRNA network. Notably, the low expression of IRF4 was demonstrated to be associated with a significantly poorer overall survival in the GEPIA2 database, which was also verified by the immunofluorescence of the sections in Human Protein Atlas (HPA). The upstream miRNA corresponding to IRF4 is hsa-miR-1228-3p.

Conclusion: From above concern, it can conclude that hsa_circ_0000301/hsa-miR-1228-3p/IRF4 may be involved in the occurrence and development of cervical cancer. However, the specific mechanism should be further studied and confirmed.
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http://dx.doi.org/10.1186/s12885-021-08331-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140416PMC
May 2021

Comprehensive analysis of the prognostic value and immune function of the gene in gynecological cancers.

Am J Transl Res 2021 15;13(4):2041-2059. Epub 2021 Apr 15.

Department of Gynecology and Obstetrics, The People's Hospital of China Three Gorges University/The First People's Hospital of Yichang Yichang 443000, Hubei, P. R. China.

Gynecologic cancer is a serious global healthcare issue with high rates of mortality and morbidity. In recent years, tumor immunity and immunotherapy have attracted extensive attention for treatment of gynecological cancers. Indoleamine 2, 3-dioxygenase 1 (IDO1) plays a critical role in cancer immune escape, and its inhibition has been explored for immune-targeted therapies for many malignancies. However, knowledge about IDO1 involvement in the pathogenesis of gynecological cancers and its therapeutic potential is still evolving. In the current study, we integrated bioinformatics analysis of the prognostic value and immune function of IDO1 in gynecologic malignancies using Oncomine, GEPIA, HPA, TIMER, TISIDB, SurvExpress and Metascape database. Comprehensive analysis revealed that the transcription levels of IDO1 were significantly overexpressed in patients with gynecologic cancers, and IDO1-co-expressed gene signatures may be useful potential prognostic markers for gynecologic cancers. Furthermore, increased IDO1 expression correlated with immune infiltration cells, immune marker sets, and immunomodulators in gynecological cancers. These findings suggest that IDO1 plays an important role in immune infiltration and could potentially be an immunotherapeutic target for gynecological cancers. However, future large-scale and comprehensive research is required to validate our results.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129385PMC
April 2021

Association of Carotid Atherosclerosis With White Matter Hyperintensity in an Asymptomatic Japanese Population: A Cross-Sectional Study.

Front Cardiovasc Med 2021 29;8:665573. Epub 2021 Apr 29.

Department of Neurosurgery, The First People's Hospital of Changde, Changde, China.

A limited number of scholars concentrated on the relationship between carotid atherosclerosis (CAS) and white matter hyperintensity (WMH) (i.e., CAS-WMH relationship). The current research aimed to clarify the CAS-WMH relationship in Japanese population. All participants underwent MRI of head and ultrasonography of the carotid artery. WMH was diagnosed from MRI results. The carotid ultrasound findings, carotid artery plaque score (PS), and plaque number (PN) could be achieved to indicate the severity of CAS. We also employed multivariate logistic regression models to estimate the CAS-WMH relationship. Interaction and stratified analyses were undertaken on the basis of a number of factors (e.g., gender, age, smoking status, drinking habit, and history of chronic diseases). A total of 1,904 Japanese subjects were included, and the prevalence of WMH was 54.8% (1,044/1,904). It was unveiled that frequency of CAS was greater in cases with WMH. In a fully adjusted model, high PS was associated with the frequency of WMH, followed by high PN. Further analyses revealed a dose-response relationship between PS and incidence of WMH. PS and PN exhibited the greatest influences on determining the frequency of WMH, highlighting the potentially important pathophysiological role of large artery atherosclerosis in intensifying WMH.
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http://dx.doi.org/10.3389/fcvm.2021.665573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118638PMC
April 2021

Rapid mechanochemical synthesis of polyanionic cathode with improved electrochemical performance for Na-ion batteries.

Nat Commun 2021 May 14;12(1):2848. Epub 2021 May 14.

Key Laboratory for Renewable Energy, Beijing Key Laboratory for New Energy Materials and Devices, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.

Na-ion batteries have been considered promising candidates for stationary energy storage. However, their wide application is hindered by issues such as high cost and insufficient electrochemical performance, particularly for cathode materials. Here, we report a solvent-free mechanochemical protocol for the in-situ fabrication of sodium vanadium fluorophosphates. Benefiting from the nano-crystallization features and extra Na-storage sites achieved in the synthesis process, the as-prepared carbon-coated Na(VOPO)F nanocomposite exhibits capacity of 142 mAh g at 0.1C, higher than its theoretical capacity (130 mAh g). Moreover, a scaled synthesis with 2 kg of product was conducted and 26650-prototype cells were demonstrated to proof the electrochemical performance. We expect our findings to mark an important step in the industrial application of sodium vanadium fluorophosphates for Na-ion batteries.
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http://dx.doi.org/10.1038/s41467-021-23132-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121810PMC
May 2021

Calcium Phosphate Cement Causes Nucleus Pulposus Cell Degeneration through the ERK Signaling Pathway.

Open Life Sci 2020 6;15:209-216. Epub 2020 May 6.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006, China.

While calcium phosphate cement (CPC) is recognized as one of the most likely substitutes for the conventional Polymethylmethacrylate (PMMA), there are very few studies about its intradiscal leakage consequences. Herein, the goal of our study was to examine the effect of CPC particles on the ERK (extracellular regulatory kinase) pathway in human nucleus pulposus cell (HNPC) degeneration. Different concentrations of CPC particles (0.00‰, 0.01‰, 0.05‰, 0.1‰ v/v) were added to human nucleus pulposus cell cultures. After 10 days of treatment, HNPC biological behaviors and degeneration degree were analyzed by CCK-8 assay, crystal violet staining, flow cytometer and western blot. The effect of CPC on the ERK pathway was also analyzed by western blot. After activating the ERK path by overexpressing Ras, HNPCs' biological behaviors and degeneration degree were analyzed again. We found that CPC particles had a negative effect on human nucleus pulposus cells (HNPCs), which are mainly reflected in cell growth and the cell cycle. After activation of the ERK signaling pathway, the negative effects of CPC on cell growth and the cell cycle were significantly reduced and the degeneration degree of HNPCs was reversed. CPC particles can probably block the activation of the ERK pathway, thus causing the HNPCs' degeneration.
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http://dx.doi.org/10.1515/biol-2020-0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114789PMC
May 2020

Biodegradability of Micro/Nanomotors: Challenges and Opportunities.

Adv Healthc Mater 2021 May 6:e2100335. Epub 2021 May 6.

School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, China.

Micro/nanomotors (MNMs) are miniature machines that can convert chemical or external energy into their own mechanical motions. In previous decades, significant efforts have been made to improve the performance of MNMs. For practical applications, the biodegradability of MNMs is an important aspect that must be considered, particularly in the biomedical field. In this review, recent progress in the biodegradability of MNMs and their potential applications are summarized. Different biodegradable materials, including metals and polymers, or other strategies for the fabrication of MNMs, are presented. Current challenges and future perspectives are also discussed.
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http://dx.doi.org/10.1002/adhm.202100335DOI Listing
May 2021

Pharmacokinetics of 10-Hydroxy Mesaconitine in Rat Plasma by Ultra-Performance Liquid Chromatography-Tandem Quadrupole Mass Spectrometry.

J Anal Methods Chem 2021 19;2021:6640184. Epub 2021 Apr 19.

The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Lishui 323000, China.

Mesaconitine is the predominant active ingredient in Debx. The compound 10-hydroxy mesaconitine is one known metabolite of mesaconitine and is toxic. In order to better understand its pharmacokinetics, UPLC-MS/MS was used in this paper to measure the concentration of 10-hydroxy mesaconitine in the plasma of rats after oral (5 mg/kg) and intravenous (0.1 mg/kg) administration of 10-hydroxy mesaconitine. The concentrations of 10-hydroxy mesaconitine in rat plasma measured in the standard curve covered the range of 0.3-60 ng/mL. The intraday and interday precisions of the samples of 10-hydroxy mesaconitine in rat plasma were lower than 15%. In addition, the accuracies ranged between 96.0% and 109.3%, the matrix effects ranged between 88.9% and 98.1%, and the recoveries were all higher than 79.1%. The AUC values were 23.6 ± 5.9 and 207.6 ± 72.9 ng/mL·h for intravenous and oral administration, respectively, and the bioavailability of 10-hydroxy mesaconitine was 17.6%. Lastly, was 1.3 ± 0.6 h and 3.1 ± 0.4 h for intravenous and oral administration, respectively.
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http://dx.doi.org/10.1155/2021/6640184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075697PMC
April 2021

Power Spectrum Features of Acupoint Bioelectricity Signal.

Evid Based Complement Alternat Med 2021 12;2021:6638807. Epub 2021 Apr 12.

State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, 19 Fourth Ring Road North, Haidian District, Beijing 100090, China.

Background: Since the 1950s, many studies have been conducted on the electrical properties of acupuncture points (acupoints), especially their bio-resistance characteristics. Results of such studies have been inconclusive due to factors such as sweat gland density and compounding factors of applying electrical stimulation. In this study, a power spectrum instrument was used to assess the power spectrum and power of acupoints and nonacupoints without electrical stimulation. Using such instrumentation, specificity of electrical signals of acupoints was also explored.

Methods: Thirty-six subjects (29 females, 7 males) participated in the study. Stainless steel acupuncture needles (diameter 0.35 mm; length 50 mm) were used. Five acupoints were tested: ST 36, SP 6, GB 39, GB 37, and K I9. Four control sites 0.5-1.0 cm adjacent to each acupoint were chosen. After needle insertion into the acupoint and control sites, the needles were attached to the power spectrum instrument to acquire any electrical signals. Acquire signals were analyzed using self-written software.

Results: Power spectrum difference between acupoint and nonacupoint signals was 0-2 Hz. Results of -test or signed rank sum test ( = 0.05) found that electrical signals between acupoints and nonacupoints were markedly different ( < 0.05).

Conclusion: Acupoint bioelectricity signals are higher than adjacent nonacupoints. The most significant difference is distributed between 0 Hz and 2 Hz.
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http://dx.doi.org/10.1155/2021/6638807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057873PMC
April 2021

Enhanced Peroxidase-mimicking Activity of Plasmonic Gold-modified Mn O Nanocomposites through Photoexcited Hot Electron Transfer.

Chem Asian J 2021 Jun 11;16(12):1603-1607. Epub 2021 May 11.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433, P. R. China.

Enzyme-mimicking artificial nanomaterials often termed nanozymes have broad applications in many fields, including biosensing, pollutant degradation and cancer diagnosis. Herein, we introduce a plasmonic gold nanoparticle-modified Mn O nanozyme (Mn O -Au). Visible or near infrared light excitation into the plasmonic absorption band of the surface-bound gold nanoparticles enhances the catalytic oxidation of tetramethylbenzidine (TMB). The mechanism of light-enhanced peroxidase activity is proposed based on the Mn O conduction band mediated hot electron transfer from photoexcited gold nanoparticles to H O which undergoes further oxygen-oxygen bond cleavage to yield hydroxyl radical. The surface decoration of plasmonic gold nanoparticles endows Mn O -Au to be a light-regulated nanozyme.
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http://dx.doi.org/10.1002/asia.202100337DOI Listing
June 2021

Effects of dacomitinib on the pharmacokinetics of poziotinib and .

Pharm Biol 2021 Dec;59(1):457-464

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Context: Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic.

Objective: This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats.

Materials And Methods: Twelve Sprague-Dawley rats were randomly divided into two groups: the test group (20 mg/kg dacomitinib for 14 consecutive days) and the control group (equal amounts of vehicle). Each group was given an oral dose of 10 mg/kg poziotinib 30 min after administration of dacomitinib or vehicle at the end of the 14 day administration. The concentration of poziotinib in plasma was quantified by UPLC-MS/MS. Both effects of dacomitinib on poziotinib and the mechanism of the observed inhibition were studied in rat liver microsomes and human liver microsomes.

Results: When orally administered, dacomitinib increased the AUC, and decreased CL of poziotinib ( < 0.05). The IC values of M1 in RLM, HLM and CYP3A4 were 11.36, 30.49 and 19.57 µM, respectively. The IC values of M2 in RLM, HLM and CYP2D6 were 43.69, 0.34 and 0.11 µM, respectively, and dacomitinib inhibited poziotinib by a mixed way in CYP3A4 and CYP2D6. The results of the experiments were consistent with those of the experiments.

Conclusions: This research demonstrates that a drug-drug interaction between poziotinib and dacomitinib possibly exists when readministered with poziotinib; thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of poziotinib in clinical settings.
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http://dx.doi.org/10.1080/13880209.2021.1914114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079061PMC
December 2021

Co-delivery of IOX1 and doxorubicin for antibody-independent cancer chemo-immunotherapy.

Nat Commun 2021 04 23;12(1):2425. Epub 2021 Apr 23.

Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.

Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream β-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells' P-glycoproteins (P-gp) through the JMJD1A/β-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-22407-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065121PMC
April 2021

Cocktail Therapy of Fosthiazate and Cupric-Ammoniun Complex for Citrus Huanglongbing.

Front Plant Sci 2021 31;12:643971. Epub 2021 Mar 31.

MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.

Huanglongbing (HLB) is a destructive citrus bacterial disease caused by Liberibacter asiaticus (.Las) and cannot be cured by current pesticides. Root lesion and juveniles were observed in HLB-affected citrus tree roots. We hypothesize that root treatment with fosthiazate (FOS) and Cupric-Ammonium Complex (CAC) will improve the root growth and inhibit HLB. CAC is a broad spectrum fungicide and can promote growth of crops. FOS kills and protects roots from damage by harmful bacteria such as .Las. After 90 days of combination treatment of FOS and CAC through root drenches, the citrus grew new roots and its leaves changed their color to green. The inhibition rate of .Las reached more than 90%. During treatment process, the chlorophyll content and the root vitality increased 396 and 151%, respectively, and starch accumulation decreased by 88%. Transmission electron microscopy (TEM) and plant tissue dyeing experiments showed that more irregular swollen starch granules existed in the chloroplast thylakoid system of the HLB-infected leaves. This is due to the blocking of their secretory tissue by starch. TEM and flow cytometry experiments showed the synergistic effects of FOS and CAC. A transcriptome analysis revealed that the treatment induced the differential expression of the genes which involved 103 metabolic pathways. These results suggested that the cocktail treatment of FOS and CAC may effectively kill various pathogens including .Las on citrus root and thus effectively control HLB.
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http://dx.doi.org/10.3389/fpls.2021.643971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044827PMC
March 2021

Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion-drug conjugates with cell-membrane affinity.

Nat Biomed Eng 2021 Apr 15. Epub 2021 Apr 15.

Zhejiang Key Laboratory of Smart BioMaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.

Effective anticancer nanomedicines need to exhibit prolonged circulation in blood, to extravasate and accumulate in tumours, and to be taken up by tumour cells. These contrasting criteria for persistent circulation and cell-membrane affinity have often led to complex nanoparticle designs with hampered clinical translatability. Here, we show that conjugates of small-molecule anticancer drugs with the polyzwitterion poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) have long blood-circulation half-lives and bind reversibly to cell membranes, owing to the negligible interaction of the polyzwitterion with proteins and its weak interaction with phospholipids. Adsorption of the polyzwitterion-drug conjugates to tumour endothelial cells and then to cancer cells favoured their transcytosis-mediated extravasation into tumour interstitium and infiltration into tumours, and led to the eradication of large tumours and patient-derived tumour xenografts in mice. The simplicity and potency of the polyzwitterion-drug conjugates should facilitate the design of translational anticancer nanomedicines.
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http://dx.doi.org/10.1038/s41551-021-00701-4DOI Listing
April 2021

Association between red blood cell distribution width and in-hospital mortality in acute myocardial infarction.

Medicine (Baltimore) 2021 Apr;100(15):e25404

Department of Cardiovascular, The First People's Hospital of Changde City, Changde, Hunan, China.

Abstract: Previous studies have shown an independent association between increased red cell distribution width (RDW) and mortality after acute myocardial infarction (AMI). However, evidence regarding the predictive significance of repeated measures of RDW in patients with AMI remains scarce. We aimed to investigate the association between the dynamic profile of RDW and in-hospital mortality in patients with AMI.This was a cross-sectional study. We extracted clinical data from the Medical Information Mart for Intensive Care IIIV1.4 database. Demographic data, vital signs, laboratory test data, and comorbidities were collected from the database. The clinical endpoint was in-hospital mortality. Cox proportional hazards models were used to evaluate the prognostic values of basic RDW, and the Kaplan-Meier method was used to plot survival curves. Subgroup analyses were performed to measure mortality across various subgroups. The repeated-measures data were compared using a generalized additive mixed model.In total, 3101eligible patients were included. In multivariate analysis, adjusted for age, sex, and ethnicity, RDW was a significant risk predictor of in-hospital mortality. Furthermore, after adjusting for more confounding factors, RDW remained a significant predictor of in-hospital mortality (tertile 3 vs tertile 1: hazard ratio 2.3; 95% confidence interval 1.39-4.01; P for trend <.05). The Kaplan-Meier curve for tertiles of RDW indicated that survival rates were highest when RDW was ≤13.2% and lowest when RDW was ≥14.2% after adjustment for age, sex, and ethnicity. During the intensive care unit stay, the RDW of nonsurvivors progressively increased until death occurred.Our findings showed that a higher RDW was associated with an increased risk of in-hospital mortality in patients with AMI.
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http://dx.doi.org/10.1097/MD.0000000000025404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052072PMC
April 2021

MRI-based radiomics signature for pretreatment prediction of pathological response to neoadjuvant chemotherapy in osteosarcoma: a multicenter study.

Eur Radiol 2021 Mar 30. Epub 2021 Mar 30.

Department of Radiology, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics. Guangdong Province), 183 Zhongshan Da Dao Xi, Guangzhou, 510630, Guangdong, China.

Objective: To develop and validate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for preoperative prediction of pathologic response to neoadjuvant chemotherapy (NAC) in patients with osteosarcoma.

Methods: We retrospectively enrolled 102 patients with histologically confirmed osteosarcoma who received chemotherapy before treatment from 4 hospitals (68 in the primary cohort and 34 in the external validation cohort). Quantitative imaging features were extracted from contrast-enhanced fat-suppressed T1-weighted images (CE FS T1WI). Four classification methods, i.e., the least absolute shrinkage and selection operator logistic regression (LASSO-LR), support vector machine (SVM), Gaussian process (GP), and Naive Bayes (NB) algorithm, were compared for feature selection and radiomics signature construction. The predictive performance of the radiomics signatures was assessed with the area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis (DCA).

Results: Thirteen radiomics features selected based on the LASSO-LR classifier were adopted to construct the radiomics signature, which was significantly associated with the pathologic response. The prediction model achieved the best performance between good and poor responders with an AUC of 0.882 (95% CI, 0.837-0.918) in the primary cohort. Calibration curves showed good agreement. Similarly, findings were validated in the external validation cohort with good performance (AUC, 0.842 [95% CI, 0.793-0.883]) and good calibration. DCA analysis confirmed the clinical utility of the selected radiomics signature.

Conclusion: The constructed CE FS T1WI-radiomics signature with excellent performance could provide a potential tool to predict pathologic response to NAC in patients with osteosarcoma.

Key Points: • The radiomics signature based on multicenter contrast-enhanced MRI was useful to predict response to NAC. • The prediction model obtained with the LASSO-LR classifier achieved the best performance. • The baseline clinical characteristics were not associated with response to NAC.
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http://dx.doi.org/10.1007/s00330-021-07748-6DOI Listing
March 2021

FSTL1 promotes growth and metastasis in gastric cancer by activating AKT related pathway and predicts poor survival.

Am J Cancer Res 2021 1;11(3):712-728. Epub 2021 Mar 1.

The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, P. R. China.

Accumulating evidence on the role of Follistatin-like protein 1 (FSTL1) in tumorigenesis and cancer progression is conflicting. Nevertheless, the underlying mechanisms by which FSTL1 contributes to gastric cancer (GC) remain unknown. This study shows that FSTL1 was frequently upregulated in primary GC tissues and significantly correlated with infiltrating depth, lymph node metastasis, unfavorable tumor stage and poor prognosis of GC. Down or up-regulation of FSTL1 inhibited or increased, respectively, the proliferation by reducing apoptosis, clonogenicity, migration and invasion of GC cells . Moreover, the higher expression of FSTL1 promoted subcutaneous xenograft tumor growth and lung/liver tumor metastasis . Furthermore, we demonstrate that FSTL1 is involved in regulation of the AKT signaling through analyzing databases and experimental results. Mechanistic studies showed that FSTL1 promoted proliferation, migration and invasion in GC, at least partially, by activating AKT via regulating TLR4/CD14. In all, this study highlights the role of the FSTL1-TLR4/CD14-AKT axis, which provided novel insights into the mechanism of growth and metastasis in GC for the first time.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994156PMC
March 2021

Temperature-Sensitive Lipid-Coated Carbon Nanotubes for Synergistic Photothermal Therapy and Gene Therapy.

ACS Nano 2021 04 22;15(4):6517-6529. Epub 2021 Mar 22.

Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, Dalian Minzu University, Dalian 116600, China.

The combination of photothermal therapy (PTT) and gene therapy (GT) shows great potential to achieve synergistic anti-tumor activity. However, the lack of a controlled release of genes from carriers remains a severe hindrance. Herein, peptide lipid (PL) and sucrose laurate (SL) were used to coat single-walled carbon nanotubes (SCNTs) and multi-walled carbon nanotubes (MCNTs) to form bifunctional delivery systems (denoted SCNT-PS and MCNT-PS, respectively) with excellent temperature-sensitivity and photothermal performance. CNT/siRNA suppressed tumor growth by silencing survivin expression while exhibiting photothermal effects under near-infrared (NIR) light. SCNT-PS/siRNA showed very high anti-tumor activity, resulting in the complete inhibition of some tumors. It was highly efficient for systemic delivery to tumor sites and to facilitate siRNA release owing to the phase transition of the temperature-sensitive lipids, due to PL and SL coating. Thus, SCNT-PS/siRNA is a promising anti-tumor nanocarrier for combined PTT and GT.
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http://dx.doi.org/10.1021/acsnano.0c08790DOI Listing
April 2021

Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes and in an Cocktail Method.

Front Pharmacol 2020 5;11:593518. Epub 2021 Jan 5.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). As poziotinib is partially metabolized by CYPs, cocktail probes are used to study the interaction between drugs metabolized by each CYP subtype. Midazolam, bupropion, dextromethorphan, tolbutamide, chlorzoxazone, phenacetin, and their metabolites were used to examine the effects of poziotinib on the activity of cyp1a2, 2b1, 2d1, 2c11, 2e1, and 3a1/2, respectively. The experiment was carried out by using rat liver microsomes (RLMs), whereas the experiment involved the comparison of the pharmacokinetic parameters of the probes after co-administration with poziotinib to rats to those of control rats treated with only probes. UPLC-MS/MS was used to detect the probes and their metabolites in rat plasma and rat liver microsomes. The results revealed that the half-maximal inhibitory concentration values of bupropion and tolbutamide in RLMs were 8.79 and 20.17 μM, respectively, indicating that poziotinib showed varying degrees of inhibition toward cyp2b1 and cyp2c11. Poziotinib was a competitive inhibitor of cyp2b1 and cyp2c11, with Ki values of 16.18 and 17.66 μM, respectively. No time- or concentration-dependence of inhibition by poziotinib was observed toward cyp2b1 and cyp2c11 in RLMs. Additionally, no obvious inhibitory effects were observed on the activity of cyp1a2, cyp2d1, cyp2e1, and cyp3a1/2. analysis revealed that bupropion, tolbutamide, phenacetin, and chlorzoxazone showed significantly different pharmacokinetic parameters after administration ( < 0.05); there was no significant difference in the pharmacokinetic parameters of dextromethorphan and midazolam. These results show that poziotinib inhibited cyp2b1 and cyp2c11, but induced cyp1a2 and cyp2e1 in rats. Thus, poziotinib inhibited cyp2b1 and cyp2c11 activity in rats, suggesting the possibility of interactions between poziotinib and these CYP substrates and the need for caution when combining them in clinical settings.
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http://dx.doi.org/10.3389/fphar.2020.593518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970697PMC
January 2021

Inhibitor of DNA-binding family regulates the prognosis of ovarian cancer.

Future Oncol 2021 May 17;17(15):1889-1906. Epub 2021 Mar 17.

Department of Gynecology & Obstetrics, The People's Hospital of China Three Gorges University/The First People's Hospital of Yichang, Hubei, 443000, PR China.

The mechanistic role of inhibitor of DNA binding or differentiation (ID) family in ovarian cancer (OC) has remained unclear. We used the Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, SurvExpress, PROGgene V2, TIMER, and FunRich to evaluate the prognostic value of IDs in patients with OC. the mRNA transcripts of all IDs were markedly downregulated in OC compared with normal tissue. The prognostic value of IDs was also explored within the subtypes, pathological stages, clinical stages and TP53 mutational status. The group with low-risk IDs showed relatively good overall survival (OS) compared with the high-risk group ID1/3/4 may be exploited as promising prognostic biomarkers and therapeutic targets in OC patients.
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http://dx.doi.org/10.2217/fon-2020-1006DOI Listing
May 2021

Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma.

Sci Rep 2021 Mar 11;11(1):5710. Epub 2021 Mar 11.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.

The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.
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http://dx.doi.org/10.1038/s41598-021-84831-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952570PMC
March 2021

Excellent electrochemical stability of Co3O4 array with carbon hybridization derived from metal-organic framework.

Nanotechnology 2021 Mar 11. Epub 2021 Mar 11.

Southern University of Science and Technology, Shenzhen, Guangdong, CHINA.

Hybrid supercapacitors have attracted considerable attention for the use in the energy storage systems due to the simultaneous possession of high power and energy. Herein, Co3O4 array with amorphous carbon on Ni foam has been derived from the Co-MOF. The electrochemical dynamics and energy storage mechanism of the prepared electrode have been investigated, which reveal the enhancement of the capacitive behavior with the scan rate. The electrochemically active specific surface area (ECSA) of our sample is calculated as 1416 cm2 for per square centimeter of electrode. The prepared material exhibits an excellent electrochemical performance (3.17 F·cm-2 at 1 mA·cm-2 and 2.076 F·cm-2 at 30 mA·cm-2). Further, the long-term life shows 96.7% capacitance retention at 50 mV·s-1 after 20,000 cycles in KOH aqueous electrolyte. The coulomb efficiency is noted to range from 95% to 100% even after 20,000 cycles. Further, the symmetrical solid-state supercapacitor represents a wide operating voltage range and high scan rate for practical applications. Three charged solid-state supercapacitors are observed to lit 160 parallel green LEDs (20 mA, 2.2V) for approximately 50 s. These findings from this study confirm the potential of Co3O4 array with carbon hybridization as an effective supercapacitor electrode material.
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http://dx.doi.org/10.1088/1361-6528/abedefDOI Listing
March 2021

Towards the understanding of hyperthermophilic methanogenesis from waste activated sludge at 70 °C: Performance, stability, kinetic and microbial community analyses.

Waste Manag 2021 Apr 8;125:172-181. Epub 2021 Mar 8.

Key Laboratory of Coal Science and Technology, Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, China.

Anaerobic digestion is promising for waste activated sludge (WAS) degradation. However, conventional processes were generally stuck with limited hydrolysis and poor pathogen destruction. Hyperthermophilic digestion at 70 °C has drawn attention in overcoming those issues at a relatively low energy requirement and operating difficulties. In order to illuminate its operation characteristics, a single-stage hyperthermophilic digester was controlled at 70 °C and operated continuously to degrade WAS. 88.7 mL/g VS of methane yield could be achieved in the hyperthermophilic system, fourfold higher than that in the mesophilic system. Kinetic analysis revealed that hyperthermophilic digestion was advantageous in converting the non-degradable fraction. Consequently, hydrolysis under the hyperthermophilic condition was able to be significantly improved. Above 10 d was necessary for the hyperthermophilic system to gain such a high methane production. In the case of stability, the organic loading of higher than 10.2 g VS/L/d resulted in increasing limitation from methanogenesis and accumulation of propionic, butyric and valeric acids. In addition to the dominant acetoclastic genus Methanothrix for methane production in the hyperthermophilic system, two hydrogenotrophic methanogens Methanospirillum and Methanothermobacter reached 18.84% and 8.31%, respectively. The genus Coprothermobacter, affiliated with the phylum Firmicutes, made more contribution to protein hydrolysis in the hyperthermophilic digester.
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http://dx.doi.org/10.1016/j.wasman.2021.02.037DOI Listing
April 2021

Associations between air pollutant exposure and renal function: A prospective study of older adults without chronic kidney disease.

Environ Pollut 2021 May 16;277:116750. Epub 2021 Feb 16.

Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China. Electronic address:

We used real-world exposure scenarios to evaluate the effect of six ambient air pollutant (PM, PM, NO, SO, CO, and O) exposure on renal function among older adults without chronic kidney disease (CKD). We recruited 169 older adults without CKD in Beijing, China, for a longitudinal study from 2016 to 2018. The Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (EPI) equations were employed to derive the estimated glomerular filtration rate (eGFR). A linear mixed-effects model with random intercepts for participants was employed to determine the effects of air pollutants on renal function evaluated on the basis of eGFR and urinary albumin/creatinine ratio at different exposure windows (1-, 2-, 3-, 5-, 7-, 14-, 28-, 45-, and 60-days moving averages). An interquartile range (IQR) increase in NO for was associated with significant decreases of in eGFR (MDRD equation) [percentage changes: -4.49 (95% confidence interval: -8.44, -0.37), -5.51 (-10.43, -0.33), -2.26 (-4.38, -0.08), -3.71 (-6.67, -0.65), -5.44 (-9.58, -1.11), -5.50 (-10.24, -0.51), -6.15 (-10.73, -1.33), and -6.34 (-11.17, -1.25) for 1-, 2-, 5-, 7-, 14-, 28-, 45-, and 60-days moving averages, respectively] and in eGFR (EPI equation) [percentage changes: -5.04 (-7.09, -2.94), -6.25 (-8.81, -3.62), -5.16 (-7.34, -2.92), -5.10 (-7.85, -2.28), -5.83 (-8.23, -3.36), -6.04 (-8.55, -3.47) for 1-, 2-, 14-, 28-, 45-, and 60-days moving averages, respectively]. In two-pollutant model, only the association of NO exposure with eGFR remained robust after adjustment for any other pollutant. This association was stronger for individuals with hypertension for the EPI equation or BMI <25 kg/m for the MDRD equation at lags 1 and 1-2. Our findings suggest that NO exposure is associated with eGFR reduction among older adults without CKD for short (1-, 2-days) and medium (14-, 28-, 45-, 60-days) term exposure periods; thus, NO exposure may contribute to renal impairment.
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http://dx.doi.org/10.1016/j.envpol.2021.116750DOI Listing
May 2021

The Relationship Between the Serum Anion Gap and All-Cause Mortality in Acute Pancreatitis: An Analysis of the MIMIC-III Database.

Int J Gen Med 2021 19;14:531-538. Epub 2021 Feb 19.

Cardiovascular Medicine Department, The First People's Hospital of Changde, Changde City, Hunan Province, 415000, People's Republic of China.

Purpose: We aimed to investigate the relationship between the serum anion gap (AG) and all-cause mortality in patients with acute pancreatitis (AP) in intensive care units (ICUs).

Patients And Methods: In this retrospective cohort analysis, data of patients with AP were extracted from the Medical Information Mart for Intensive Care database (version III). We collected the maximum serum AG value within the first 24 hours of ICU admission. The main outcome was 90-day all-cause mortality. A multivariate Cox proportional hazard regression model was used to examine the association between the serum AG and mortality. The restricted cubic spline curve was used to confirm a non-linear relationship between serum AG values and mortality.

Results: Of the 279 patients included in the study, 87 (31.18%) died. The serum AG value was positively associated with 90-day all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.02-1.14), after adjusting for age, sex, alcohol consumption, congestive heart failure, diabetes mellitus, hypertension, eGFR, albumin, and the SOFA score. There was a non-linear relationship between serum AG values and mortality after adjusting for potential confounders. We used a two-piecewise regression model to obtain a threshold inflection point value of 13.8 mmol/L. The HR and the 95% CI on the left inflection point were 0. 82 (0.61-1.09; p = 0.1719), and on the right inflection point were 1.15 (1.08-1.23; p < 0.0001).

Conclusion: The relationship between all-cause mortality in patients with acute pancreatitis and serum AG values was non-linear. All-cause mortality and serum AG values were positively correlated when the serum AG value was >13.8 mmol/L.
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http://dx.doi.org/10.2147/IJGM.S293340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903165PMC
February 2021