Publications by authors named "Mao Li"

628 Publications

Effect of lactic acid bacteria, molasses, and their combination on the fermentation quality and bacterial community of cassava foliage silage.

Anim Sci J 2021 ;92(1):e13635

Japan International Research Center for Agricultural Sciences, Tsukuba, Ibaraki, Japan.

This study investigated the effects of LAB inoculants (L) and molasses (M) on the microbial community and fermentation quality of cassava foliage (CF). The small segments (about 2-3 cm) CF were ensiled in plastic bags and incubated at normal temperature (25°C). Four treatments were carried out as follows: control (no additives, CK), LAB inoculants (Lactobacillus plantarum, L), molasses (M), and LAB in combination with molasses (LM). The LAB and molasses obviously altered the bacterial community structure of the CF silage and enhanced the fermentation quality. The combination addition could increase the abundance of Lactobacillus and reduce the Pseudomonas. The LAB and molasses also significantly elevated the lactic acid concentration (P < 0.001) and decreased the pH (P < 0.001), as well as the concentrations of acetic acid, propionic acid, butyric acid, and ammonia-N (P < 0.05). In addition, the combination treatment displayed more effective results on silage fermentation. The LAB and molasses improved the fermentation quality of the CF silage by altering the bacterial community structure. Furthermore, the bacterial community was significantly correlated with fermentation indexes.
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http://dx.doi.org/10.1111/asj.13635DOI Listing
January 2021

Quantitative dissection of color patterning in the foliar ornamental coleus.

Plant Physiol 2021 Aug 15. Epub 2021 Aug 15.

Donald Danforth Plant Science Center, St Louis, Missouri 63132, USA.

Coleus (Coleus scutellarioides) is a popular ornamental plant that exhibits a diverse array of foliar color patterns. New cultivars are currently hand selected by both amateur and experienced plant breeders. In this study, we reimagine breeding for color patterning using a quantitative color analysis framework. Despite impressive advances in high-throughput data collection and processing, complex color patterns remain challenging to extract from image datasets. Using a phenotyping approach called "ColourQuant," we extract and analyze pigmentation patterns from one of the largest coleus breeding populations in the world. Working with this massive dataset, we can analyze quantitative relationships between maternal plants and their progeny, identify features that underlie breeder-selections, and collect and compare public input on trait preferences. This study is one of the most comprehensive explorations into complex color patterning in plant biology and provides insights and tools for exploring the color pallet of the plant kingdom.
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http://dx.doi.org/10.1093/plphys/kiab393DOI Listing
August 2021

Combination of certainty and uncertainty: Using FusionGAN to create abstract paintings.

Neural Netw 2021 Sep 9;144:443-454. Epub 2021 Sep 9.

College of Computer Science, Sichuan University, Chengdu 610065, PR China.

In the study of generative art, it is relatively easy at present to achieve a high degree of certainty or uncertainty. However, the combination of certainty and uncertainty has always been an area of difficulty in generative art. In this paper, we present a novel FusionGAN system to automate the generation of abstract paintings. These generated abstract paintings combine the factors of certainty and uncertainty. First, we collect an APdataset consisting of three parts: abstract paintings drawn by artists, sketches, and abstract paintings generated by other neural network methods. We then train the proposed FusionGAN system on the collected dataset to learn the expression of abstract paintings. Corresponding to the two-step operation of the combination of certainty and uncertainty in the artist's creation, the proposed FusionGAN system is also divided into two steps for the generation of abstract paintings. More specifically, the first step is the basic structure establishment, which corresponds to the fundamental certainty element in the painting creation. The second step is the realization of details, which integrates the uncertain details based on the basic structure. The experimental results achieved by our system in abstract painting generation enrich the diversity of artistic creation and have been recognized by art institutions, with some results displayed on their websites.
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http://dx.doi.org/10.1016/j.neunet.2021.09.001DOI Listing
September 2021

Transcriptomic and Mutational Analysis Discovering Distinct Molecular Characteristics Among Chinese Thymic Epithelial Tumor Patients.

Front Oncol 2021 8;11:647512. Epub 2021 Sep 8.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Introduction: Thymic epithelial tumors (TETs) are malignancies arising from the epithelium of the thymic gland, rare but with relatively favorable prognosis. TETs have different pathological subtypes: thymomas and thymic carcinoma, and they show different clinical characteristics regarding prognosis, pathology, and molecular profiles, etc. Although some studies have investigated the pathogenesis of TETs, more molecular data is still needed to further understand the underlying mechanisms among different TETs subtypes and populations.

Methods: In this study, we performed targeted gene panel sequencing and whole transcriptome sequencing on the tumor tissues from 27 Chinese TET patients, including 24 thymomas (A, AB, and B subtypes) and 3 thymic squamous cell carcinomas. We analyzed the genetic variations and differentially expressed genes among multiple TET subtypes. Moreover, we compared our data with the published The Cancer Genome Atlas (TCGA) TET data on both the genetic and transcriptomic levels.

Results: Compared with the TCGA TET genomic data, we found that and were the most frequently mutated genes (each with a frequency of 11%, 3/27). These mutations were not mutually exclusive, since one B1 thymoma showed mutations of both genes. The mutation was mainly enriched in subtype A and AB thymomas, consistent with the previous reports. RNA-seq results unveiled that the genes related to thymus development (, and ) were highly expressed in certain TET subtypes, implicating that the developmental process of thymus might be linked to the tumorigenesis of these subtypes. We found high expression of (PD-L1) in B2 and B3 thymoma samples, and validated its expression using immunohistochemistry (IHC). Based on the expression profiles, we further established a machine learning model to predict the myasthenia gravis status of TET patients and achieved 90% sensitivity and 70.6% specificity in the testing cohort.

Conclusion: This study provides the first genomic and transcriptomic analysis of a Chinese TET cohort. The high expression of genes involved in thymus developmental processes suggests the potential association between tumorigenesis of TETs and dysregulation of developmental pathways. The high expression of PD-L1 in B2 and B3 thymomas support the potential application of immunotherapy on certain thymoma subtypes.
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http://dx.doi.org/10.3389/fonc.2021.647512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456088PMC
September 2021

A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation.

Drug Deliv Transl Res 2021 Sep 24. Epub 2021 Sep 24.

Department of Biomedical Engineering, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA.

Background Extending the lifespan of subcutaneous insulin administration sets and infusion pumps requires overcoming unreliable insulin delivery induced by dermal reactions. All commercially available insulin formulations contain insulin phenolic preservatives (IPP), which stabilize the insulin molecule but result in unwanted cell and tissue toxicity. Mast cells, which are the first line of defense once the epithelium is breached, are particularly abundant beneath the skin surface. Thus, we hypothesize a sequence of events initiated by device insertion that activates skin mast cells (MC) that subsequently trigger neutrophil and monocyte/macrophage recruitment. The ensuing inflammatory response compromises effective insulin infusion therapy. Methods We employed a non-genetic, pharmacological approach to MC membrane stabilization using Cromolyn sodium (CS), which inhibits MC degranulation. These studies were conducted in our modified air pouch mouse model using non-diabetic and streptozotocin induced diabetic mice. We evaluated the impact of systemic CS through intraperitoneal injections, as well as the impact of local CS through co-infusion, on infusion catheter insertion and IPP-induced inflammation. Results CS at a concentration of 50 mg/kg minimized inflammation triggered in response to insulin phenolic preservatives present in standard insulin formulations. The resultant degree of tissue inflammation was comparable to that observed with saline injections. Conclusion Targeting MC has the potential to extend the longevity of insulin infusion sets by mitigating the inflammatory response. Future studies should be directed at employing other MC models, such as newer Cre/loxP mouse strains, to confirm the sentinel role of MC in insulin infusion therapy.
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http://dx.doi.org/10.1007/s13346-021-01070-wDOI Listing
September 2021

Preoperative splenic artery embolism followed by splenectomy is safe and effective in patients with sinistral portal hypertension.

Langenbecks Arch Surg 2021 Sep 19. Epub 2021 Sep 19.

Pancreatology Department, West China Hospital, Sichuan University, Chengdu, China.

Background: Although preoperative splenic artery embolism (SAE) has been widely used for splenomegaly, the efficiency and safety of preoperative SAE in patients with sinistral portal hypertension (SPH) is unknown.

Methods: We designed a retrospective cohort of SPH patients who received preoperative SAE in our hospital (February 2018 to September 2020) and compared to those who received splenectomy only, in terms of intraoperative and postoperative outcomes.

Results: In all, 59 patients (18 patients received preoperative SAE) were analyzed. The median age was 44.7 years. Preoperative SAE reduced the intraoperative blood loss (637.0 vs. 420.3 ml, P = 0.041) and operation time (174.0 vs. 141.5 min, P = 0.012). The incidence of complications including postoperative pancreatic fistula (POPF), bleeding, and thromboembolism was comparable. Multivariate analysis showed that SAE was a protective factor for intraoperative blood loss and operation time, while prior pancreatic pseudocyst/abscess was a risk factor.

Conclusions: Preoperative SAE could reduce intraoperative blood loss and operation time in SPH patients without increasing the incidence of complications compared to splenectomy only.
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http://dx.doi.org/10.1007/s00423-021-02329-zDOI Listing
September 2021

Machine learning-based CT radiomics model distinguishes COVID-19 from non-COVID-19 pneumonia.

BMC Infect Dis 2021 Sep 8;21(1):931. Epub 2021 Sep 8.

Department of Radiology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19, Xiuhua St, Xiuying Dic, Haikou, Hainan, 570311, People's Republic of China.

Background: To develop a machine learning-based CT radiomics model is critical for the accurate diagnosis of the rapid spreading coronavirus disease 2019 (COVID-19).

Methods: In this retrospective study, a total of 326 chest CT exams from 134 patients (63 confirmed COVID-19 patients and 71 non-COVID-19 patients) were collected from January 20 to February 8, 2020. A semi-automatic segmentation procedure was used to delineate the volume of interest (VOI), and radiomic features were extracted. The Support Vector Machine (SVM) model was built on the combination of 4 groups of features, including radiomic features, traditional radiological features, quantifying features, and clinical features. By repeating cross-validation procedure, the performance on the time-independent testing cohort was evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.

Results: For the SVM model built on the combination of 4 groups of features (integrated model), the per-exam AUC was 0.925 (95% CI 0.856 to 0.994) for differentiating COVID-19 on the testing cohort, and the sensitivity and specificity were 0.816 (95% CI 0.651 to 0.917) and 0.923 (95% CI 0.621 to 0.996), respectively. As for the SVM models built on radiomic features, radiological features, quantifying features, and clinical features, individually, the AUC on the testing cohort reached 0.765, 0.818, 0.607, and 0.739, respectively, significantly lower than the integrated model, except for the radiomic model.

Conclusion: The machine learning-based CT radiomics models may accurately classify COVID-19, helping clinicians and radiologists to identify COVID-19 positive cases.
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http://dx.doi.org/10.1186/s12879-021-06614-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424152PMC
September 2021

Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

JAMA Oncol 2021 Sep 2. Epub 2021 Sep 2.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

Importance: Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).

Objective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.

Design, Setting, And Participants: This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC.

Interventions: Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.

Main Outcomes And Measures: The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.

Results: A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P < .001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P < .001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals.

Conclusions And Relevance: In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC.

Trial Registration: ClinicalTrials.gov Identifier: NCT02767804.
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http://dx.doi.org/10.1001/jamaoncol.2021.3523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414368PMC
September 2021

Efficacy and Safety of Liquid Nitrogen Cryotherapy for Lichen Simplex Chronicus: A Meta-Analysis.

Dermatology 2021 Aug 26:1-10. Epub 2021 Aug 26.

Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: Lichen simplex chronicus (LSC) is characterized by localized lichenification and intense itching. It has been reported that the added use of liquid nitrogen cryotherapy (LNC) for LSC has significant efficacy and notable safety. Therefore, we conducted a meta-analysis based on existing randomized controlled trials (RCTs).

Method: We searched RCTs on LNC for LSC published up to August 2020 using various databases, including PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Biomedicine (CBM), Chinese Scientific Journals Database (VIP), and WanFang Database. Other studies were manually identified using the references cited in reviews. We applied fixed- or random-effects models, and all analyses were performed using Review Manager 5.4 software.

Results: Twelve RCTs involving 1,066 participants provided eligible data for the meta-analysis. Based on the clinical effective rate, LNC treatment of LSC (risk ratio, RR 1.25, p = 0.005, I2 = 82%) was superior to controls. Subgroup analysis showed that the use of LNC alone (RR 1.04, I2 = 95%, p > 0.05) is not more effective than other therapies in the treatment of LSC, but the addition of LNC to the existing treatment increases the total clinical efficacy. Furthermore, the combined effect of LNC and topical medication (RR 1.39, I2 = 0%, p < 0.0001) was better than that of LNC and oral medication (RR 1.30, I2 = 0%, p < 0.00001). Greater frequency of LNC treatment did not improve the efficacy (thrice a week: RR 1.39 [1.21, 1.60]; twice a week: RR 1.27; once every 2 weeks: RR 1.32). Data from 6 RCTs with 508 participants showed no significant difference in AEs (p = 0.31) associated with added LNC treatment.

Conclusion: The addition of LNC (applying a cotton swab soaked with liquid nitrogen to wipe the lesion for approximately 10 s each time) to topical ointments, is effective and safe in the treatment of LSC. Increasing the treatment frequency of LNC did not necessarily improve the efficacy.
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http://dx.doi.org/10.1159/000518897DOI Listing
August 2021

miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats.

Biomed Res Int 2021 14;2021:5535788. Epub 2021 Aug 14.

Internal Medicine Department, Cardiology, College of Medicine, Jouf University, Sakaka, Aljouf, Saudi Arabia.

PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3'UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.
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http://dx.doi.org/10.1155/2021/5535788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382530PMC
October 2021

Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine.

Front Immunol 2021 4;12:694959. Epub 2021 Aug 4.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Avian Tembusu virus (TMUV) is a novel flavivirus causing severe egg drop and fatal encephalitis in avian in Asia. In the present study, we screened the structural and functional requirements of TMUV capsid protein (CP) for viral morphogenesis using reverse genetics methods in combination with replicon packaging assays. TMUV-CP showed dramatic functional and structural flexibility, and even though 44 residues were removed from the N-terminus, it was still capable of packaging replicon RNA; in addition, 33 residues were deleted from the C-terminus (containing nearly the entire α4-helix), and infectious particles were still produced, although α4-α4' is supposedly vital for CP dimerization and nucleocapsid formation. We further analyzed two mutants (ΔC20-43 and ΔC64-96 viruses) with relatively large deletions that still replicated well in BHK-21 cells. Our data indicate that internal deletions within CP impaired viral replication or assembly, resulting in attenuated virus proliferation in cells and attenuated virulence in duck embryos, and these deletion mutations are quite stable in cell culture. An assay indicated that both ΔC20-43 virus and ΔC64-96 virus were highly attenuated in ducklings but still immunogenic. Single-dose immunization with ΔC20-43 virus or ΔC64-96 virus could protect ducklings from a lethal challenge with good antigen clearance. Together, our data shed light on replication/assembly defective TMUV with internal deletions in CP and provide an effective approach to attenuate viral virulence in live vaccines without changing the antigen composition.
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http://dx.doi.org/10.3389/fimmu.2021.694959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371329PMC
August 2021

CAFs shape myeloid-derived suppressor cells to promote stemness of intrahepatic cholangiocarcinoma via 5-lipoxygenase.

Hepatology 2021 Aug 13. Epub 2021 Aug 13.

Department of Immunology and Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

Background And Aims: We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth via recruiting of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression via acting its receptor Leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC).

Approach And Results: RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from ICC patients. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 mainly expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identify the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 that were elevated in CAF-educated MDSCs or blockade of BLT2 that was preferentially expressed in stem-like ICC cells significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient derived-xenograft (PDX) models.

Conclusions: Our study reveals a previously unrecognized role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs and suggests 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.
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http://dx.doi.org/10.1002/hep.32099DOI Listing
August 2021

Correction to: The germline/somatic DNA damage repair gene mutations modulate the therapeutic response in Chinese patients with advanced pancreatic ductal adenocarcinoma.

J Transl Med 2021 Aug 12;19(1):345. Epub 2021 Aug 12.

Department of Abdominal Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1186/s12967-021-02997-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361738PMC
August 2021

Transcriptome and Proteomic Analysis Reveals Up-Regulation of Innate Immunity-Related Genes Expression in Caprine Herpesvirus 1 Infected Madin Darby Bovine Kidney Cells.

Viruses 2021 07 2;13(7). Epub 2021 Jul 2.

College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea.

Caprine herpesvirus 1 (CpHV-1) is a member of the alpha subfamily of herpesviruses, which is responsible for genital lesions and latent infections in goat populations worldwide. In this study, for the first time, the transcriptome and proteomics of CpHV-1 infected Madin Darby bovine kidney (MDBK) cells were explored using RNA-Sequencing (RNA-Seq) and isobaric tags for relative and absolute quantitation-liquid chromatography tandem mass spectrometry (iTRAQ-LC-MS/MS) technology, respectively. RNA-Seq analysis revealed 81 up-regulated and 19 down-regulated differentially expressed genes (DEGs) between infected and mock-infected MDBK cells. Bioinformatics analysis revealed that most of these DEGs were mainly involved in the innate immune response, especially the interferon stimulated genes (ISGs). Gene Ontology (GO) enrichment analysis results indicated that the identified DEGs were significantly mainly enriched for response to virus, defense response to virus, response to biotic stimulus and regulation of innate immune response. Viral carcinogenesis, the RIG-I-like receptor signaling pathway, the cytosolic DNA-sensing pathway and pathways associated with several viral infections were found to be significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Eleven selected DEGs (Mx1, RSAD2, IFIT1, IFIT2, IFIT5, IFIH1, IFITM3, IRF7, IRF9, OAS1X and OAS1Y) associated with immune responses were selected, and they exhibited a concordant direction both in RNA-Seq and quantitative real-time RT-PCR analysis. Proteomic analysis also showed significant up-regulation of innate immunity-related proteins. GO analysis showed that the differentially expressed proteins were mostly enriched in defense response and response to virus, and the pathways associated with viral infection were enriched under KEGG analysis. Protein-protein interaction network analysis indicated most of the DEGs related to innate immune responses, as DDX58(RIG-I), IFIH1(MDA5), IRF7, Mx1, RSAD2, OAS1 and IFIT1, were located in the core of the network and highly connected with other DGEs. Our findings support the notion that CpHV-1 infection induced the transcription and protein expression alterations of a series of genes related to host innate immune response, which helps to elucidate the resistance of host cells to viral infection and to clarify the pathogenesis of CpHV-1.
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http://dx.doi.org/10.3390/v13071293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310103PMC
July 2021

miR-133a-3p inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells by regulating ankyrin repeat domain 44.

Gen Physiol Biophys 2021 Jul;40(4):329-339

Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, Dongcheng District, Beijing, China.

In this study, we aimed to identify the specific microRNAs (miRNAs) that are involved in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) mice, and to further explore the mechanism by which these miRNAs regulate osteogenic differentiation. Based on the existing studies, the expression of seven miRNAs in BMSCs from OVX mice was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of miR-133a-3p and osteogenesis-related genes (runt-related transcription factor 2 (Runx2), Osterix, alkaline phosphatase (ALP), and osteopontin) in BMSCs treated with miR-133a-3p mimics or inhibitors was detected by qRT-PCR or Western blotting. Osteogenesis efficiency was determined using ALP and alizarin red staining. The effector-target relationship between miR-133a-3p and ankyrin repeat domain 44 (ANKRD44) was confirmed by bioinformatics and a dual luciferase assay. Among the seven selected miRNAs, miR-133a-3p expression was significantly increased in BMSCs from OVX mice. Overexpression of miR-133a-3p dramatically inhibited the expression of osteogenesis-related genes in BMSCs and reduced ALP activity and mineralization. However, these processes were markedly ameliorated upon miR-133a-3p inhibition. Moreover, miR-133a-3p appeared to target ANKRD44, and the ANKRD44 expression was negatively regulated by miR-133a- 3p. Furthermore, ANKRD44 upregulation eliminated the anti-osteogenic differentiation effects of miR-133a-3p in BMSCs. Thus, our results indicated that miR-133a-3p inhibits the osteogenic differentiation of BMSCs by suppressing ANKRD44.
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http://dx.doi.org/10.4149/gpb_2020038DOI Listing
July 2021

Effects of General Anesthesia Combined with Epidural Anesthesia on Cognitive Dysfunction and Inflammatory Markers of Patients after Surgery for Esophageal Cancer: A Randomised Controlled Trial.

J Coll Physicians Surg Pak 2021 Aug;31(8):885-890

Department of Anesthesiology, Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.

Objective: To evaluate the impact of general anesthesia (GA) combined with epidural anesthesia (GAEA) on postoperative cognitive dysfunction (POCD) and inflammatory markers in patients with esophageal cancer (EC).   Study Design: A randomised controlled trial.

Place And Duration Of Study: Department of Anesthesiology, Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China, from August 2019 to April 2020.

Methodology: SPSS was used to randomly divide 142 cases into two groups, namely: the GA (n=71) and GAEA (n=71) categories. 128 candidates were used in this study. Cognitive function and the levels of interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis markers α (TNF-α) in serum were evaluated at baseline, 1, 3 and 7 days after operation by Montreal Cognitive Assessment (MoCA) and enzyme-linked immunosorbent assay (ELISA), respectively. Pearson correlation analysis was used to assess the interrelationships between MoCA score and inflammatory markers levels.

Results: Compared to the GA group (n=64), the GAEA category (n=64) showed significantly higher MoCA score on 1 day and 3 days postoperatively (all p <0.05). IL-6, IL-8 and TNF-α in the GA group were significantly increased on 1, 3 and 7 days after surgery (all p <0.05). Pearson correlation analysis indicated that the three inflammatory markers were inversely correlated with cognitive function score (all p <0.05). The postoperative adverse events between the two groups were comparable (all p >0.05).

Conclusion: Combining general and epidural anesthesia may reduce the incidence of POCD in patients undergoing esophagectomy by suppressing inflammatory response. Key Words: General anesthesia, Epidural anesthesia, Esophageal cancer, Postoperative cognitive dysfunction, Inflammatory markers.
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http://dx.doi.org/10.29271/jcpsp.2021.08.885DOI Listing
August 2021

Can Neighborhood Social Infrastructure Modify Cognitive Function? A Mixed-Methods Study of Urban-Dwelling Aging Americans.

J Aging Health 2021 Oct 23;33(9):772-785. Epub 2021 Jul 23.

Social Environment and Health Program, Survey Research Center, Institute for Social Research, 1259University of Michigan, Ann Arbor, MI, USA.

Socialization predicts cognitive aging outcomes. Neighborhoods may facilitate socially engaged aging and thus shape cognition. We investigated places where older adults socialized and whether availability of these sites was associated with cognitive outcomes. Qualitative analysis of interviews and ethnography with 125 older adults (mean age 71 years) in Minneapolis identified where participants socialized outside of home. This informed quantitative analysis of a national sample of 21,151 older Americans (mean age at baseline 67 years) from the study. Multilevel generalized additive models described associations between access to key social places and cognitive function and decline. Qualitative analysis identified eateries, senior centers, and civic groups as key places to socialize. We identified significant positive associations between kernel density of senior centers, civic/social organizations, and cognitive function. Specific neighborhood social infrastructures may support cognitive health among older adults aging in place.
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http://dx.doi.org/10.1177/08982643211008673DOI Listing
October 2021

Insulin Derived Fibrils Induce Cytotoxicity and Trigger Inflammation in Murine Models.

J Diabetes Sci Technol 2021 Jul 21:19322968211033868. Epub 2021 Jul 21.

Department of Biomedical Engineering, Integrative Biosciences Center. Wayne State University, Detroit, MI, USA.

Background: Effective exogenous insulin delivery is the cornerstone of insulin dependent diabetes mellitus management. Recent literature indicates that commercial insulin-induced tissue reaction and cellular cytotoxicity may contribute to variability in blood glucose as well as permanent loss of injection or infusion site architecture and function. It is well accepted that insulin formulations are susceptible to mechanical and chemical stresses that lead to insulin fibril formation. This study aims to characterize and toxicity, as well as pro-inflammatory activity of insulin fibrils.

Method: cell culture evaluated cytotoxicity and fibril uptake by macrophages and our modified murine air-pouch model quantified inflammatory activity. The latter employed FLOW cytometry and histopathology to characterize fibril-induced inflammation , which included fibril uptake by inflammatory phagocytes.

Results: These studies demonstrated that insulin derived fibrils are cytotoxic to cells . Furthermore, inflammation is induced in the murine air-pouch model and in response, macrophages uptake fibrils both and .

Conclusions: Administration of insulin fibrils can lead to cytotoxicity in macrophages. data demonstrate insulin fibrils to be pro-inflammatory which over time can lead to cumulative cell/tissue toxicity, inflammation, and destructive wound healing. Long term, these tissue reactions could contribute to loss of insulin injection site architecture and function.
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http://dx.doi.org/10.1177/19322968211033868DOI Listing
July 2021

Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial.

Lancet Respir Med 2021 09 21;9(9):1021-1029. Epub 2021 Jul 21.

Thoracic Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study.

Methods: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m on days 1 and 8 of each cycle plus cisplatin 75 mg/m on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m plus cisplatin 75 mg/m on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797.

Findings: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group.

Interpretation: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection.

Funding: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(21)00134-XDOI Listing
September 2021

Identification of Two Novel Candidate Genetic Variants Associated With the Responsiveness to Influenza Vaccination.

Front Immunol 2021 1;12:664024. Epub 2021 Jul 1.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, China.

Background: Annual vaccination is the most effective prevention of influenza infection. Up to now, a series of studies have demonstrated the role of genetic variants in regulating the antibody response to influenza vaccine. However, among the Chinese population, the relationship between genetic factors and the responsiveness to influenza vaccination has not been clarified through genome-wide association study (GWAS).

Method: A total of 1,968 healthy volunteers of Chinese descent were recruited and 1,582 of them were available for the subsequent two-stage analysis. In the discovery stage, according to our inclusion criteria, 123 of 1,582 subjects were selected as group 1 and received whole-genome sequencing to identify potential variants and genes. In the verification stage, 29 candidate variants identified by GWAS were selected for further validation in 481 subjects in group 2. Besides, we also analyzed nine variants from previously published reports in our study.

Results: Multivariate logistic regression analysis showed that compared with the TT genotype of rs2281929, the TC + CC genotype was associated with a lower risk of low responsiveness to influenza vaccination adjusted for gender and age (Group 2: = 7.75E-05, OR = 0.466, 95%CI = 0.319-0.680; Combined group: = 1.18E-06, OR = 0.423, 95%CI = 0.299-0.599). In the combined group, rs2455230 GC + CC genotype was correlated with a lower risk of low responsiveness to influenza vaccination compared with the GG genotype ( = 8.90E-04, OR = 0.535, 95%CI = 0.370-0.774), but the difference was not statistically significant in group 2 ( = 0.008). The antibody fold rises of subjects with rs2281929 TT genotype against H1N1, H3N2,and B were all significantly lower than that of subjects with TC + CC genotype ( < 0.001). Compared with rs2455230 GC + CC carriers, GG carriers had lower antibody fold rises to H1N1 ( = 0.001) and B ( = 0.032). The GG genotype of rs2455230 tended to be correlated with lower antibody fold rises ( = 0.096) against H3N2, but the difference was not statistically significant. No correlation was found between nine SNPs from previously published reports and the serological response to influenza vaccine in our study.

Conclusion: Our study identified two novel candidate missense variants, rs2281929 and rs2455230, were associated with the immune response to influenza vaccination among the Chinese population. Identifying these variants will provide more evidence for future research and improve the individualized influenza vaccination program.
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http://dx.doi.org/10.3389/fimmu.2021.664024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281270PMC
July 2021

The germline/somatic DNA damage repair gene mutations modulate the therapeutic response in Chinese patients with advanced pancreatic ductal adenocarcinoma.

J Transl Med 2021 07 12;19(1):301. Epub 2021 Jul 12.

Department of Abdominal Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine.

Methods: The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan-Meier survival analyses were performed by the R version 3.6.1.

Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutation was an independent prognostic factor for survival analysis of advanced PDAC patients (p = 0.032). For DDR mutant patients, treatment with platinum-based chemotherapy (p = 0.0096) or olaparib (p = 0.018) respectively improved the overall survival. No statistical difference between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significantly improved OS to DDR-mutated patients than the naive DDR group (p = 0.14).

Conclusions: In this retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy in Chinese patients. However, the value of DDR mutation in the prediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.
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http://dx.doi.org/10.1186/s12967-021-02972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273977PMC
July 2021

Fatty acid oxidation: driver of lymph node metastasis.

Cancer Cell Int 2021 Jul 3;21(1):339. Epub 2021 Jul 3.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Fatty acid oxidation (FAO) is the emerging hallmark of cancer metabolism because certain tumor cells preferentially utilize fatty acids for energy. Lymph node metastasis, the most common way of tumor metastasis, is much indispensable for grasping tumor progression, formulating therapy measure and evaluating tumor prognosis. There is a plethora of studies showing different ways how tumor cells metastasize to the lymph nodes, but the role of FAO in lymph node metastasis remains largely unknown. Here, we summarize recent findings and update the current understanding that FAO may enable lymph node metastasis formation. Afterward, it will open innovative possibilities to present a distinct therapy of targeting FAO, the metabolic rewiring of cancer to terminal cancer patients.
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http://dx.doi.org/10.1186/s12935-021-02057-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254237PMC
July 2021

Exosomal microRNA let-7-5p from Cysticercus Prompted Macrophage to M2 Polarization through Inhibiting the Expression of C/EBP δ.

Microorganisms 2021 Jun 29;9(7). Epub 2021 Jun 29.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou 730046, China.

, the larval stage of , causes serious illness in rabbits that severely impacts the rabbit breeding industry. An inhibitive Th2 immune response can be induced by let-7-enriched exosomes derived from cysticercus. However, the underlying molecular mechanisms are not completely understood. Here, we report that exosomal miR-let-7-5p released by cysticercus played a critical role in the activation of M2 macrophages. We found that overexpression of let-7-5p in M1 macrophages decreased M1 phenotype expression while promoting polarization to the M2 phenotype, which is consistent with experimental data in exosome-treated macrophages alone. In contrast, knockdown of let-7-5p in exosome-like vesicles promoted M1 polarization and decreased M2 phenotype expression. Furthermore, down-regulation of transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ resulted in the decrease of M1 phenotype markers and increase of M2 phenotype markers. These results suggested that let-7 enriched in exosome-like vesicles from metacestodes can induce M2 macrophage polarization via targeting C/EBP δ, which may be involved in macrophage polarization induced by metacestodes. The finding helps to expand our knowledge of the molecular mechanism of immunosuppression and Th2 immune response induced by metacestodes.
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http://dx.doi.org/10.3390/microorganisms9071403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307393PMC
June 2021

Detecting and Quantifying Polyhaloaromatic Environmental Pollutants by Chemiluminescence-Based Analytical Method.

Molecules 2021 Jun 2;26(11). Epub 2021 Jun 2.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Polyhaloaromatic compounds (XAr) are ubiquitous and recalcitrant in the environment. They are potentially carcinogenic to organisms and may induce serious risks to the ecosystem, raising increasing public concern. Therefore, it is important to detect and quantify these ubiquitous XAr in the environment, and to monitor their degradation kinetics during the treatment of these recalcitrant pollutants. We have previously found that unprecedented intrinsic chemiluminescence (CL) can be produced by a haloquinones/HO system, a newly-found OH-generating system different from the classic Fenton system. Recently, we found that the degradation of priority pollutant pentachlorophenol by the classic Fe(II)-Fenton system could produce intrinsic CL, which was mainly dependent on the generation of chloroquinone intermediates. Analogous effects were observed for all nineteen chlorophenols, other halophenols and several classes of XAr, and a novel, rapid and sensitive CL-based analytical method was developed to detect these XAr and monitor their degradation kinetics. Interestingly, for those XAr with halohydroxyl quinoid structure, a Co(II)-mediated Fenton-like system could induce a stronger CL emission and higher degradation, probably due to site-specific generation of highly-effective OH. These findings may have broad chemical and environmental implications for future studies, which would be helpful for developing new analytical methods and technologies to investigate those ubiquitous XAr.
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http://dx.doi.org/10.3390/molecules26113365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199721PMC
June 2021

TDP-43 and Phosphorylated TDP-43 Levels in Paired Plasma and CSF Samples in Amyotrophic Lateral Sclerosis.

Front Neurol 2021 14;12:663637. Epub 2021 Jun 14.

Department of Neurology, First Medical Center, Chinese PLA General Hospital, Beijing, China.

The aim of this study was to measure both plasma and cerebrospinal fluid (CSF) TAR DNA-binding protein 43 (TDP-43) and phosphorylated TDP-43 (pTDP-43) levels in sporadic amyotrophic lateral sclerosis (sALS) patients, and to compare them with that of healthy controls. The correlation between plasma or CSF TDP-43/pTDP-43 and clinical indicators of ALS patients was assessed. Paired plasma and CSF TDP-43/pTDP-43 levels in 69 ALS patients and 59 healthy controls were measured by sandwich ELISA. Time to generalization (TTG), an indicator suggested that the time of symptoms spreading from spinal or bulbar localization to both, was evaluated in all patients screened for mutations in genes associated with ALS. Both of the plasma TDP-43 and pTDP-43 levels were significantly higher in ALS patients than HCs ( < 0.001). The pTDP-43/TDP-43 ratios in plasma were significantly higher in HCs than ALS patients ( < 0.001). The area under the curve (AUC) value was 0.924 for plasma TDP-43 level, with a 91.3% sensitivity and 91.5% specificity. Moreover, the correlation between plasma and CSF TDP-43 was observed in each ALS patient ( = 0.195, = 0.027). A correlation between CSF pTDP-43 levels and the ALSFRS-R ( = -0.245; = 0.042) was established. A correlation was observed between plasma TDP-43 levels and TTG in ALS patients, which indicated that high levels of plasma TDP-43 correlated with prolonged TTG ( = 0.415; = 0.004). The plasma TDP-43 and pTDP-43 levels might play an important role in diagnosis in the future study of ALS. The plasma TDP-43 might differentiate ALS and HC groups based on high sensitivity and specificity, and as an indicator of progression of disease.
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http://dx.doi.org/10.3389/fneur.2021.663637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236522PMC
June 2021

Deep Learning on Enhanced CT Images Can Predict the Muscular Invasiveness of Bladder Cancer.

Front Oncol 2021 11;11:654685. Epub 2021 Jun 11.

Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Background: Clinical treatment decision making of bladder cancer (BCa) relies on the absence or presence of muscle invasion and tumor staging. Deep learning (DL) is a novel technique in image analysis, but its potential for evaluating the muscular invasiveness of bladder cancer remains unclear. The purpose of this study was to develop and validate a DL model based on computed tomography (CT) images for prediction of muscle-invasive status of BCa.

Methods: A total of 441 BCa patients were retrospectively enrolled from two centers and were divided into development (n=183), tuning (n=110), internal validation (n=73) and external validation (n=75) cohorts. The model was built based on nephrographic phase images of preoperative CT urography. Receiver operating characteristic (ROC) curves were performed and the area under the ROC curve (AUC) for discrimination between muscle-invasive BCa and non-muscle-invasive BCa was calculated. The performance of the model was evaluated and compared with that of the subjective assessment by two radiologists.

Results: The DL model exhibited relatively good performance in all cohorts [AUC: 0.861 in the internal validation cohort, 0.791 in the external validation cohort] and outperformed the two radiologists. The model yielded a sensitivity of 0.733, a specificity of 0.810 in the internal validation cohort and a sensitivity of 0.710 and a specificity of 0.773 in the external validation cohort.

Conclusion: The proposed DL model based on CT images exhibited relatively good prediction ability of muscle-invasive status of BCa preoperatively, which may improve individual treatment of BCa.
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http://dx.doi.org/10.3389/fonc.2021.654685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226179PMC
June 2021

Phenolic Preservative Removal from Commercial Insulin Formulations Reduces Tissue Inflammation while Maintaining Euglycemia.

ACS Pharmacol Transl Sci 2021 Jun 26;4(3):1161-1174. Epub 2021 Apr 26.

Department of Biomedical Engineering, Integrative Biosciences Center, Wayne State University, Detroit, Michigan 48202,United States.

: Exogenous insulin therapy requires stabilization of the insulin molecule, which is achieved through the use of excipients (e.g., phenolic preservatives (PP)) that provide protein stability, sterility and prolong insulin shelf life. However, our laboratory recently reported that PP, (e.g., -creosol and phenol) are also cytotoxic, inducing inflammation and fibrosis. Optimizing PP levels through filtration would balance the need for insulin preservation with PP-induced inflammation. : Zeolite Y (Z-Y), a size-exclusion-based resin, was employed to remove PP from commercial insulin formulations (Humalog) before infusion. : PP removal significantly decreased cell toxicity and inflammation . Infusion site histological analysis after a 3 day study demonstrated that leukocyte accumulation increased with nonfiltered preparations but decreased after filtration. Additional studies demonstrated that a Z-Y fabricated filter effectively removed excess PP such that the filtered insulin solution achieved equivalent glycemic control in diabetic mice when compared to nonfiltered insulin. : This approach represents the proof of concept that using Z-Y for in-line PP removal assists in lowering inflammation at the site of insulin infusion and thus could lead to extending the functional lifespan of insulin infusion sets .
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http://dx.doi.org/10.1021/acsptsci.1c00047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205237PMC
June 2021

Mechanistic Study on Oxidative DNA Damage and Modifications by Haloquinoid Carcinogenic Intermediates and Disinfection Byproducts.

Chem Res Toxicol 2021 Jul 18;34(7):1701-1712. Epub 2021 Jun 18.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, P.R. China.

Haloquinones (XQs) are a group of carcinogenic intermediates of the haloaromatic environmental pollutants and newly identified chlorination disinfection byproducts (DBPs) in drinking water. The highly reactive hydroxyl radicals/alkoxyl radicals and quinone enoxy/ketoxy radicals were found to arise in XQs and HO or organic hydroperoxides system, independent of transition-metal ions. However, it was not clear whether these haloquinoid carcinogens and hydroperoxides can cause oxidative DNA damage and modifications, and if so, what are the underlying molecular mechanisms. We found that 8-oxodeoxyguanosine (8-oxodG), DNA strand breaks, and three methyl oxidation products could arise when DNA was treated with tetrachloro-1,4-benzoquinone and HO via a metal-independent and intercalation-enhanced oxidation mechanism. Similar effects were observed with other XQs, which are generally more efficient than the typical Fenton system. We further extended our studies from isolated DNA to genomic DNA in living cells. We also found that potent oxidation of DNA to the more mutagenic imidazolone dIz could be induced by XQs and organic hydroperoxides such as -butylhydroperoxide or the physiologically relevant hydroperoxide 13S-hydroperoxy-9Z,11E-octadecadienoic acid via an unprecedented quinone-enoxy radical-mediated mechanism. These findings should provide new perspectives to explain the potential genotoxicity, mutagenesis, and carcinogenicity for the ubiquitous haloquinoid carcinogenic intermediates and DBPs.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00158DOI Listing
July 2021

Melatonin Is a Promising Silage Additive: Evidence From Microbiota and Metabolites.

Front Microbiol 2021 26;12:670764. Epub 2021 May 26.

Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Danzhou, China.

The safe and effective storage of forage are very important. As an important storage method, ensiling can keep fresh forage for a long time with less nutritional loss. Melatonin has antioxidant and bacteriostasis, usually used as a natural preservative. The influence of melatonin on silage microbial or fermentation quality has not been clarified. In the present study, we aimed to clarify whether melatonin affected stylo () silage quality via microbiota and metabolites. Melatonin addition significantly improved the silage fermentation quality, including the increased contents of lactic acid and total acid (244.18-255.81% and 63.95-78.97%, respectively), as well as the decreased in pH and butyric acid content compare with control group. Moreover, 16S rRNA sequencing indicated that melatonin addition enhanced the silage microbial diversity indices (such as increase in Shannon indices but decrease in Simpson indices), and significantly shaped the composition of silage microbiota (such as increased abundances of , , , and , and decreased abundance of ). Melatonin addition also dramatically affected the metabolites of sylo silage, such as raised malonic acid and some amino acid metabolism(glycine, threonine, methionine and ornithine), while reduced nucleic acid metabolism(2-deoxyuridine and thymine) and carbon metabolism(allose and 2-deoxy-D-glucose). Collectively, our results confirmed that the lowest melatonin addition (5 mg/kg) could improve the fermentation quality, and the potential mechanisms might be associated with the microbiota and metabolites in stylo.
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http://dx.doi.org/10.3389/fmicb.2021.670764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187806PMC
May 2021

A shining proposal for the detection of dissolved O in aqueous medium: Self-calibrated optical sensing via a covalent hybrid structure of carbon-dots&Ru.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 25;261:120003. Epub 2021 May 25.

School of Materials Science & Engineering, Jiangsu University, Zhenjiang 212013, China.

O is a life-supporting gas and has been widely recognized as an important analyte in life science, medical care and environmental science. Optical sensing for gaseous oxygen has been widely reported owing to the simple, cost-effective and easy-to-go procedure. On the other hand, optical sensors for dissolved oxygen in aqueous media have been rarely reported, since most of them are incompatible with water, leading to poor sensitivity and linearity. In this effort, we tried the combination of Ru(II)-bpy complex and carbon dots (CDs) via covalent bonds, where bpy = bipyridine. A hybrid structure, named as [email protected], was constructed for the detection of dissolved oxygen, using Ru(II)-bpy as sensing probe and CDs as water-compatible supporting matrix. [email protected] was carefully characterized to confirm its hybrid structure. Detailed analysis suggested that its emission showed self-calibrated sensing signals for dissolved oxygen. A good linearity of 99.1% was realized. Its sensitivity (3.18) was higher than most literature values for dissolved oxygen detection. Its working equation was confirmed as a corrected Stern-Volmer equation (Lehrer mode). Good selectivity and signal stability were observed.
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http://dx.doi.org/10.1016/j.saa.2021.120003DOI Listing
November 2021
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