Publications by authors named "Jie Li"

7,119 Publications

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Targeting Plk1 sensitizes pancreatic cancer to immune checkpoint therapy.

Cancer Res 2022 Aug 11. Epub 2022 Aug 11.

University of Kentucky, Lexington, Kentucky, United States.

Polo-like kinase 1 (Plk1) plays an important role in cell cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response in pancreatic ductal adenocarcinoma (PDAC). Although targeting Plk1 to treat PDAC has been attempted in clinical trials, the results were not promising, and the mechanisms of resistance to Plk1 inhibition is poorly understood. In addition, the role of Plk1 in PDAC progression requires further elucidation. Here, we showed that Plk1 was associated with poor outcomes in PDAC patients. In an inducible transgenic mouse line with specific expression of Plk1 in the pancreas, Plk1 overexpression significantly inhibited caerulein-induced acute pancreatitis and delayed development of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Bioinformatics analyses identified the regulatory networks in which Plk1 is involved in PDAC disease progression, including multiple inflammation-related pathways. Unexpectedly, inhibition or depletion of Plk1 resulted in upregulation of PD-L1 via activation of the NFκB pathway. Mechanistically, Plk1-mediated phosphorylation of RB at S758 inhibited the translocation of NFκB to nucleus, inactivating the pathway. Inhibition of Plk1 sensitized PDAC to immune checkpoint blockade therapy through activation of an anti-tumor immune response. Together, Plk1 suppresses PDAC progression and inhibits NFκB activity, and targeting Plk1 can potentiate the efficacy of immunotherapy in PDAC.
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http://dx.doi.org/10.1158/0008-5472.CAN-22-0018DOI Listing
August 2022

Linking oxidative and reductive clusters to prepare crystalline porous catalysts for photocatalytic CO reduction with HO.

Nat Commun 2022 Aug 10;13(1):4681. Epub 2022 Aug 10.

School of Chemistry, South China Normal University, Guangzhou, 510006, P.R. China.

Mimicking natural photosynthesis to convert CO with HO into value-added fuels achieving overall reaction is a promising way to reduce the atmospheric CO level. Casting the catalyst of two or more catalytic sites with rapid electron transfer and interaction may be an effective strategy for coupling photocatalytic CO reduction and HO oxidation. Herein, based on the MOF ∪ COF collaboration, we have carefully designed and synthesized a crystalline hetero-metallic cluster catalyst denoted MCOF-TiCu with spatial separation and functional cooperation between oxidative and reductive clusters. It utilizes dynamic covalent bonds between clusters to promote photo-induced charge separation and transfer efficiency, to drive both the photocatalytic oxidative and reductive reactions. MCOF-TiCu exhibits fine activity in the conversion of CO with water into HCOOH (169.8 μmol gh). Remarkably, experiments and theoretical calculations reveal that photo-excited electrons are transferred from Ti to Cu, indicating that the Cu cluster is the catalytic reduction center.
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http://dx.doi.org/10.1038/s41467-022-32449-zDOI Listing
August 2022

Distinctive Excited State Symmetry Breaking Dynamics in Typical Donor-Acceptor-Donor Fluorophore: Strong Photoluminescence and Ultrafast Charge Separation from a Partial Charge Transfer State.

J Phys Chem Lett 2022 Aug 10:7547-7552. Epub 2022 Aug 10.

Beijing National Laboratory for Molecules Science (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Understanding the structure-property relationships in organic semiconductors is crucial for controlling their photophysical properties and developing new optoelectronic materials. Quadrupolar molecules, donor-acceptor-donor (DAD), have attracted extensive attention in various optoelectronic applications. However, the systematic studies on the differences on photophysical properties between DAD and simple donor-acceptor (DA) chromophores are rarely reported. Herein we present a comparative study on the excited state dynamics of DA and DAD fluorescence systems using theoretical calculation and transient absorption spectroscopy. Results show that DA and DAD molecules exhibit similar excited state dynamics, which are attributed to the distinctive excited-state symmetry breaking (ESSB) phenomenon observed in a DAD system. The strong photoluminescence (PL) and ultrafast charge separation (CS) from an ESSB-induced partial charge transfer (CT) state were clearly detected in different solvent environments. These results not only offer insight into the excited state dynamics of the DAD fluorescence system but also provide some basic guidelines for designing new optoelectronic materials.
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http://dx.doi.org/10.1021/acs.jpclett.2c02342DOI Listing
August 2022

Study of the Associations between Color Doppler Ultrasound Grading of Hyperthyroidism and Biochemical Data on Thyroid Function.

Int J Endocrinol 2022 30;2022:9743654. Epub 2022 Jul 30.

Department of Ultrasonography, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China.

Objective: The main study objective was to investigate the correlation between the color Doppler ultrasound grading of hyperthyroidism and the biochemical data of thyroid function.

Methods: Seventy-six patients were diagnosed with hyperthyroidism based on clinical and laboratory data at our hospital. The patients were examined using color Doppler ultrasound and laboratory investigations before starting I treatment. First, patients were divided into two groups based on the blood flow distribution determined by ultrasound. If the blood flow signal in the parenchyma was scattered and thinned, with dispersive points and discontinuous streaky distribution, the blood flow distribution area in the sample frame was less than or equal to 1/2 of the sample frame area and was judged to be level 1. If the parenchyma was filled with diffuse blood flow signals or if most areas had depicted rich blood flow distribution when the area of blood flow distribution in the sampling frame was greater than 1/2 of the sampling frame area, it was judged to be level 2. Then, the correlations between color Doppler ultrasound grading and biochemical data of thyroid function were analyzed. The indices included FT3, FT4, TSH, anti-TG, anti-TPO, and TRAb. Parameters of thyroid homeostasis, including thyroid's secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD), Jostel's TSH index, and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated and compared.

Results: Correlations were noted between color Doppler ultrasound grading and FT3, FT4, TRAb, SPINA-GT, TSHI, and TTSI. Moreover, FT3, FT4, TRAb, SPINA-GT, TSHI, and TTSI were higher in level 2 patients compared with level 1 patients.

Conclusion: Correlations were noted between color Doppler ultrasound grading and biochemical data of thyroid function.
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http://dx.doi.org/10.1155/2022/9743654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356896PMC
July 2022

Development and validation of a machine learning-derived radiomics model for diagnosis of osteoporosis and osteopenia using quantitative computed tomography.

BMC Med Imaging 2022 Aug 8;22(1):140. Epub 2022 Aug 8.

Department of Clinical Research Center, Dazhou Central Hospital, No.56 Nanyuemiao Street, Tongchuan District, Dazhou, 635000, Sichuan, China.

Background: To develop and validate a quantitative computed tomography (QCT) based radiomics model for discriminating osteoporosis and osteopenia.

Methods: A total of 635 patients underwent QCT were retrospectively included from November 2016 to November 2019. The patients with osteopenia or osteoporosis (N = 590) were divided into a training cohort (N = 414) and a test cohort (N = 176). Radiomics features were extracted from the QCT images of the third lumbar vertebra. Minimum redundancy and maximum relevance and least absolute shrinkage and selection operator were used for data dimensional reduction, features selection and radiomics model building. Multivariable logistic regression was applied to construct the combined clinical-radiomic model that incorporated radiomics signatures and clinical characteristics. The performance of the combined clinical-radiomic model was evaluated by the area under the curve of receiver operator characteristic curve (ROC-AUC), accuracy, specificity, sensitivity, positive predictive value, and negative predictive value.

Results: The patients with osteopenia or osteoporosis were randomly divided into training and test cohort with a ratio of 7:3. Six more predictive radiomics signatures, age, alkaline phosphatase and homocysteine were selected to construct the combined clinical-radiomic model for diagnosis of osteoporosis and osteopenia. The AUC of the combined clinical-radiomic model was 0.96 (95% confidence interval (CI), 0.95 to 0.98) in the training cohort and 0.96 (95% CI 0.92 to 1.00) in the test cohort, which were superior to the clinical model alone (training-AUC = 0.81, test-AUC = 0.79). The calibration curve demonstrated that the radiomics nomogram had good agreement between prediction and observation and decision curve analysis confirmed clinically useful.

Conclusions: The combined clinical-radiomic model that incorporates the radiomics score and clinical risk factors, can serve as a reliable and powerful tool for discriminating osteoporosis and osteopenia.
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http://dx.doi.org/10.1186/s12880-022-00868-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358842PMC
August 2022

Clinical impact and mechanisms in hepatitis B virus infection concurrent with non-alcoholic fatty liver disease.

Chin Med J (Engl) 2022 Aug 1. Epub 2022 Aug 1.

Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.

Abstract: Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully clear. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes and treatments for CHB patients with NAFLD. This study increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.
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http://dx.doi.org/10.1097/CM9.0000000000002310DOI Listing
August 2022

Effect of low-frequency high-intensity ultrasound (HIU) on the physicochemical properties of chickpea protein.

Food Res Int 2022 Sep 7;159:111474. Epub 2022 Jun 7.

School of Artificial Intelligence, Beijing Technology and Business University, No. 11 Fu Cheng Road, Haidian District, Beijing 100048, China. Electronic address:

The aim of this study was to improve the functional properties of chickpea protein for its potential application in the food industry. The effects of low frequency high intensity ultrasound (HIU) at different power (0-300 W) and time (15-30 min) on the rheological properties, gelation, thermal stability, solubility and microstructure of chickpea protein were tested and analyzed. Based on the analysis, it was found that HIU caused the disruption of non-covalent bonds between protein chains leading to the unfolding of chickpea. The HIU-treated chickpea isolate protein aggregates were smaller and more uniformly dispersed, with increased orderly structure, thermal stability, and exposure of hydrophobic and charged groups originally buried in the interior. The experimental results also showed that the effect of HIU did not become more pronounced with increasing power and time, as the power exceeding 150 W for 30 min led to the formation of new polymers by the interactions between the exposed non-covalent groups, which were more ordered and homogeneous than those without HIU.
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http://dx.doi.org/10.1016/j.foodres.2022.111474DOI Listing
September 2022

First Report of Anthracnose Caused by on var. in China.

Plant Dis 2022 Aug 8. Epub 2022 Aug 8.

Qingdao Agriculture University, Agronomy and Plant Protection, Chengyang, Qingdao, Qingdao, China, 266109;

Sansevieria trifasciata var. laurentii (De Wild.) N.E. Brown, commonly known as variegated snake plant or variegated mother-in-law's tongue, is a popular landscape and house plant. In September and October 2019, the obvious leaf spot symptoms were observed on the plants in a 0.2 hm2 of nursery in Qingdao city of China with incidence of 55%. The disease usually starts from the tip or edge of the leaf, initially have slightly water-soaked semi-circular or round brown lesions, which gradually expanded and coalesced into irregular shapes about 3-8 cm in diameter. Grayish brown sunken spots with dark margins that evolve into concentric rings of acervuli which were characteristic of anthracnose, and orange sticky conidial masses were observed under the moist condition. The leaves with typical anthracnose symptoms were collected and deposited in the herbarium of Qingdao agricultural university under accessions no. QDHB074-QDHB087. Subsequently 20 isolates with the same colony and morphological characteristics were obtained from ten diseased leaves by placing surface-sterilized tissue pieces with typical spots on potato dextrose agar (PDA). Colonies are floccose with grayish-white to dark olivaceous gray color, and gray black on the reverse after 14 days at 28°C. Straight conidia [15.0 to 27.5 × 3.5 to 7.0 μm in size (average 18.2 × 6.1 μm) (n = 50)] were cylindrical, aseptate, hyaline, slippery surface, most with one tapering end and the other oval. Setae were black, 185-230 μm in length, with a thin tip and septate in the middle. Appressoria [6.5 to 7.3 × 7.8 to 9.2 μm in size (average 6.8 × 8.1 μm) (n = 15)] were black to dark brown, solitary, spherical with smooth wall. The fungal isolates were identified as Colletotrichum sansevieriae Nakamura (Nakamura et al. 2006), based on the morphological characteristics. To confirm the identification, the internal transcribed spacer (ITS) and calmodulin (CAL) regions of a representative isolate HWL-1016 were amplified by primers ITS1/ITS4 (White et al. 1990) and CMD5/CMD6 (Weir et al. 2012), respectively. The 549 bp ITS (MN922517) and 597 bp CAL (OM994078) sequences had respectively 100% and 99.30% identity with the sequences from holotype species of C. sansevieriae MAFF 239721 (no. NR_152313 and LC180125). Phylogenetic tree based on ITS and CAL sequences respectively or jointly constructed by PAUP4.0 (Swofford 2002) revealed that the fungus in this study clustered with C. sansevieriae isolates (NR_152313, KC790947, HQ433226, JF911349, MN386823). Pathogenicity test of isolate HWL1016 was evaluated on five 3- to 4-month-old potted S. trifasciata var. laurentii under greenhouse conditions (27±2 °C, 16-hr light/8-hr dark photoperiod, 80% relative humidity). Conidial suspension (1×106 conidia/mL) of the isolated fungus from PDA colonies cultured for 15 days and sterile distilled water (as control) were sprayed on pin-pricked surface-sterilized (70% alcohol) leaves of potted plants, respectively. Three replications (three plants) were done for each treatment, and the experiment was repeated twice. The inoculated plants were covered with plastic films for 2 days and obvious water-soaked wounds were observed on the sixth day. After 16 days, the symptoms of the inoculated plants were similar to those in the nursery, with disease incidence reached 100%, while controls remained symptomless. C. sansevieriae was subsequently reisolated from the symptomatic tissues. Anthracnose on S. trifasciata var. laurentii caused by C. sansevieriae has been reported in Australia, Iran, Japan, Malaysia (Kee et al. 2020), South Korea, USA (Talhinhas & Baroncelli 2021), India (Gautam et al. 2012) and Thailand (Li et al. 2020). To our knowledge, this is the first report of C. sansevieriae causing anthracnose on S. trifasciata var. laurentii in China. This study will contribute to guide effective management based on pathogen.
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http://dx.doi.org/10.1094/PDIS-03-22-0673-PDNDOI Listing
August 2022

Efficacy of ablation index-guided pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

Pacing Clin Electrophysiol 2022 Aug 8. Epub 2022 Aug 8.

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Ablation index (AI) is a novel technology of ablation lesion quality to help improve homogeneity of lesion size and continuity. In this study, we aim to evaluate whether AI-guided PVI improves clinical outcomes compared to CF-guided PVI in patients with paroxysmal AF (PAF).

Methods: Patients undergoing first-time radiofrequency ablation for PAF were randomized in a 2:1 ratio to two groups: AI-guided PVI and CF-guided PVI. In the AI group, AI ≥500 was recommended at the anterior/superior/inferior walls, 350-400 at the posterior wall, and inter-lesion distance ≤4 mm. The primary endpoint is the freedom from atrial arrhythmia recurrence during 12 months follow-up, without antiarrhythmic drug therapy (ADT). The key secondary endpoints include intra-procedural efficiency and peri-procedural complications.

Results: 225 patients were randomized (AI group (n = 149) and CF group(n = 76)). First-pass isolation rate in AI group was significantly higher than that in CF group (58.3% vs. 43.4%, p = 0.035). After a median follow-up of 12.2 months, 154/225(68.4%) of patients were free from atrial arrhythmia recurrence without ADT, which was higher in AI group compared with CF group, but without significant difference (71.1% vs. 63.2%, p = 0.253). The incidence of peri-procedural complications is low and without difference between two groups.

Conclusions: AI-guided ablation provided higher acute efficacy than CF-guided ablation in PV isolation for patients with paroxysmal AF. The long-term success rate in AI group was higher than CF group, but did not reach statistical significance. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/pace.14578DOI Listing
August 2022

Synergistic Manipulation of Hydrogen Evolution and Zinc Ion Flux in Metal-Covalent Organic Frameworks for Dendrite-free Zn-based Aqueous Batteries.

Angew Chem Int Ed Engl 2022 Aug 8. Epub 2022 Aug 8.

South China Normal University, school of chemistry, Nanjing wenyuan road No. 1, 51006, Guangzhou, CHINA.

Zn-based aqueous batteries have attracted much attention because of their high theoretical-capacity, safety, and low-cost, yet the H2-evolution, qualification or inhibition mechanism investigations that are closely related to the dendrite-growth are rare and challenging. Herein, a series of zincophilic metal-covalent organic frameworks (e.g., Zn-AAn-COF, Zn-DAAQ-COF, and Zn-DAA-COF) have been explored as model-platforms to manipulate the H2-evolution and Zn2+ flux. Best of them, Zn-AAn-COF based cell only produces 0.002 mmol h-1 cm-2 H2, which is > 2 orders of magnitude lower than bare Zn. Noteworthy, it affords high stability for 3000 cycles (overpotential, < 79.1 mV) at 20 mA cm-2 in symmetric-cell and enhanced cycling-stability up to 6000 cycles at 2000 mA g-1 in the assembled full-battery. Besides, mechanistic characterizations show that Zn-AAn-COF can enhance the energy-barrier of H2-evolution and homogenize the ion-distribution or electric-filed to achieve high performance.
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http://dx.doi.org/10.1002/anie.202210871DOI Listing
August 2022

Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell-Cell Communication Network Using CellChat.

Front Cell Dev Biol 2022 22;10:919731. Epub 2022 Jul 22.

Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell-cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell-cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell-cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell-cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell-cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell-cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.
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http://dx.doi.org/10.3389/fcell.2022.919731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352955PMC
July 2022

Saponins from bitter melon reduce lipid accumulation via induction of autophagy in and HepG2 cell line.

Curr Res Food Sci 2022 22;5:1167-1175. Epub 2022 Jul 22.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.

Saponins from bitter melon (BMS) are well-known to have various biological activities, especially in the field of fat-lowering. However, many gaps remain in our knowledge of BMS-induced fat reduction and health benefits. Here, we aimed to investigate the precise mechanism of BMS in alleviating fat accumulation in and HepG2 cell line. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by phosphatidylethanolamine (PE) increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS largely depended on /FoxO1 and 30/TFEB mediated lipophagy to reduce fat deposition. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of autophagy-related proteins, such as the phosphorylated AMPK and LC3B. In conclusion, our results elucidated the underlying mechanism of bitter melon saponins interfering with lipid metabolism from the autophagy point of view, which provide new insights into a nutraceutical to mitigate obesity.
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http://dx.doi.org/10.1016/j.crfs.2022.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352806PMC
July 2022

Effect of Nanoscale Zero-Valent Iron on Arsenic Bioaccessibility and Bioavailability in Soil.

Front Chem 2022 22;10:964893. Epub 2022 Jul 22.

College of Geography and Environment, Shandong Normal University, Jinan, China.

Hand-to-mouth activity is considered to be the main way for children to come into contact with contaminated soil, and bioavailability is an important factor affecting their health risk. To reduce soil As risk to humans by oral exposure, nanoscale zero-valent iron (nZVI) has been extensively studied for immobilizing As-contaminated soil, but its efficiency has not been investigated using assay and its influence on As-RBA. In this study, two contaminated soil samples (A and B) were amended with 1% and 2% (w/w) nZVI for 56 days to study its effect on As fraction by sequence extraction, As bioaccessibility by SBRC assay, and As relative bioavailability (RBA) by the mouse liver and kidney model. Based on the sequence extraction, the As associated with the E1 (exchangeable fraction) and C2 (carbonate fraction) fractions were decreased from 3.00% to 1.68% for soil A and from 21.6% to 7.86% for soil B after being treated with 2% nZVI for 56 days. When assessing As bioaccessibility in all soils treated with nZVI by SBRC assay, it was found that As bioaccessibility was significantly higher in the gastric phase (GP) and lower in the intestinal phase (IP) ( < 0.05), and the bioaccessible Fe concentration decreased significantly from the gastric to intestinal phase at the same time. Based on the mouse liver-kidney model, the As-RBA in soil A increased from 21.6% to 22.3% and 39.9%, but in soil B decreased from 73.0% to 55.3% and 68.9%, respectively. In addition, there was a significant difference between As bioaccessibility based on GP or IP of SBRC assay and As-RBA in two soils after being treated with nZVI for 56 days. To more accurately assess the effects of nZVI human arsenic exposure, As-RBA should be considered in concert with secondary evidence provided through fraction and bioaccessibility assessments. In addition, it is necessary to develop a suitable assay to predict As-RBA in nZVI-amended soils.
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http://dx.doi.org/10.3389/fchem.2022.964893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353111PMC
July 2022

Dioscin ameliorates cisplatin-induced intestinal toxicity by mitigating oxidative stress and inflammation.

Int Immunopharmacol 2022 Aug 4;111:109111. Epub 2022 Aug 4.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Cisplatin is the most widely prescribed drug in chemotherapy, but its gastrointestinal toxicity reduces therapeutic efficacy. Oxidative stress and inflammation are considered to be the main pathogenesis of cisplatin-induced intestinal toxicity. Dioscin is a steroidal saponin with potential anti-cancer, antioxidant, and anti-inflammatory activities. In this study, we established a rat model of intestinal injury by tail vein injection of cisplatin, and intragastrically administered dioscin to evaluate its effect on intestinal injury. Biochemical markers, western blotting, qRT-PCR and histopathological staining were used to analyze intestinal injury according to various molecular mechanisms. The results revealed that dioscin significantly inhibited cisplatin-induced intestinal mucosal damage and decreased DAO levels in rats. Furthermore, dioscin activated the Nrf2/HO-1 pathway to increase the level of antioxidant enzymes and reduce the levels of MDA and HO. In addition, dioscin pretreatment significantly reduced ileum epithelial NLRP3 inflammasome formation and decreased the levels of inflammatory factors compared with the cisplatin group. In parallel, Nrf2 inhibitor ML385 blocked the therapeutic effect of dioscin in rat with cisplatin-induced intestinal toxicity. In terms of mechanisms, dioscin reversed cisplatin-induced up-regulation of MAPKs and up-regulated p-PI3K and p-AKT levels. Meanwhile, dioscin potently promoted Wnt3A/β-catenin signaling to relieve cisplatin-induced proliferation inhibition. In conclusion, our study suggests that dioscin could ameliorate the cisplatin-induced intestinal toxicity by reducing oxidative stress and inflammation.
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http://dx.doi.org/10.1016/j.intimp.2022.109111DOI Listing
August 2022

Comparative transcriptome and adaptive evolution analysis on the main liver and attaching liver of Pareuchiloglanis macrotrema.

J Appl Genet 2022 Aug 6. Epub 2022 Aug 6.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.

Pareuchiloglanis macrotrema is a glyptosternoid fish belonging to the Siluriform family and is endemic to the Qinghai-Tibet Plateau tributaries. P. macrotrema is an ideal model for studying the adaptive evolution of fish at high altitudes. P. macrotrema has two attaching livers connected to the main liver, a common feature in most Sisoridae fishes but is a special phenomenon relative to other vertebrates. Using RNA-Seq, 42 differentially expressed genes were found between the main liver and attaching liver, of which 31 were upregulated and 11 were downregulated in the main liver. The major differentially expressed genes between the main liver and attaching liver of P. macrotrema are related to metabolism, immunity, and digestive processes. Meanwhile, a comparative transcriptome analysis was carried out on P. macrotrema fish and six non-plateau Siluriformes fishes. We found 268 positively selected genes in P. macrotrema that are related to energy metabolism, immunity, and hypoxic responses. The findings of this study highlight the gene expression differences between the main liver and attaching livers of Sisoridae fishes and provide greater insight into the evolution of Tibetan fishes.
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http://dx.doi.org/10.1007/s13353-022-00712-0DOI Listing
August 2022

The influence of alkali-modified biochar on the removal and release of Zn in bioretention systems: Adsorption and immobilization mechanism.

Environ Pollut 2022 Aug 2:119874. Epub 2022 Aug 2.

College of Environmental Science and Engineering, Ocean University of China, Qingdao, 266100, China; Key Laboratory of Marine Environment and Ecology, Ministry of Education of China, Ocean University of China, Qingdao, 266100, China; Shandong Provincial Key Laboratory of Marine Environment and Geological Engineering, Ocean University of China, Qingdao, 266100, China.

Generally, Zn in stormwater runoff is considered as low toxicity, but in the senarios of roads and zinc-based materials roof runoff, the concentration of Zn becomes extremely high and cannot be ignored. Bioretention systems are used to remove heavy metals from stormwater runoff, while Zn adsorption is insufficient by conventional filler and is prone to secondary release when exposed to acid rain or high salinity runoff. This study integrated batch experiments and density functional theory calculation to investigate the mechanisms of how KOH-modified biochar (KBC) influences the removal and release of Zn in bioretention systems. The results revealed that KBC adsorbed 89.0-97.5% Zn in the influent, the main adsorption mechanism were complexation and precipitation, and precipitation is more important. In addition, 67% of Zn was immoblized as the residual form by KBC. In acidic and saline runoff, KBC reduced Zn secondary release by 43.6% and 37.08% compared to the results in the absence of KBC, which was attributed to the convertion of most dissolved Zn in acidic and saline runoff into residual Zn. Therefore, KBC has a considerable application potential not only to decontaminate the runoff of roads and Zn-containing roofs, but also to deal with secondary Zn release in acid rain or under the treatment of snow-melting agents.
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http://dx.doi.org/10.1016/j.envpol.2022.119874DOI Listing
August 2022

Characterizing and comparing microbial community and biofilm structure in three nitrifying moving bed biofilm reactors.

J Environ Manage 2022 Aug 3;320:115883. Epub 2022 Aug 3.

Australian Centre for Water and Environmental Biotechnology, The University of Queensland, St Lucia, QLD, 4072, Australia. Electronic address:

This study investigated biofilm establishment, biofilm structure, and microbial community composition of biofilms in three laboratory-scale moving bed biofilm reactors. These reactors were filled with three types of plastic carriers with varied depths of living space for microbial growth. The reactors were operated under the same influent and operational conditions. Along with the operation, the results showed that carriers with grids of 50 μm in height delayed the biofilm development and formed the thinnest biofilm and a carpet-like structure with the lowest α-diversity. In comparison, another two carriers with grids of 200 and 400 μm in height formed thick biofilms and large colonies with more voids and channels. Quantified properties of biofilm thickness, biomass, heterogeneity, portion of the biofilm exposed to the nutrient, and maximum diffusion distance were examined, and the results demonstrated that they almost (except for heterogeneity) strongly correlated to the α-diversity of microbial community. These illustrate that depth of living space, as an important parameter for carrier, could drive the formation of biofilm structure and community composition. It improves understanding of influencing factors on biofilm establishment, structure and its microbial community, and would be helpful for the design of biofilm processes.
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http://dx.doi.org/10.1016/j.jenvman.2022.115883DOI Listing
August 2022

Single-Cell Transcriptomics Reveals Killing Mechanisms of Antitumor Cytotoxic CD4 TCR-T Cells.

Front Immunol 2022 19;13:939940. Epub 2022 Jul 19.

Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, China.

T cell receptor-engineered T cells (TCR-Ts) have emerged as potent cancer immunotherapies. While most research focused on classical cytotoxic CD8 T cells, the application of CD4 T cells in adoptive T cell therapy has gained much interest recently. However, the cytotoxic mechanisms of CD4 TCR-Ts have not been fully revealed. In this study, we obtained an MHC class I-restricted MART-1-specific TCR sequence based on the single-cell V(D)J sequencing technology, and constructed MART-1-specific CD4 TCR-Ts and CD8 TCR-Ts. The antitumor effects of CD4 TCR-Ts were comparable to those of CD8 TCR-Ts and . To delineate the killing mechanisms of cytotoxic CD4 TCR-Ts, we performed single-cell RNA sequencing and found that classical granule-dependent and independent cytolytic pathways were commonly used in CD4 and CD8 TCR-Ts, while high expression of and various costimulatory receptors were unique features for cytotoxic CD4 TCR-Ts. Further signaling pathway analysis revealed that transcription factors Runx3 and Blimp1/Tbx21 were crucial for the development and killing function of cytotoxic CD4 T cells. Taken together, we report the antitumor effects and multifaceted killing mechanisms of CD4 TCR-Ts, and also indicate that MHC class I-restricted CD4 TCR-Ts could serve as potential adoptive T cell therapies.
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http://dx.doi.org/10.3389/fimmu.2022.939940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343810PMC
August 2022

Double Pump Sequential Constant Citrate Anticoagulation in General Hemodialysis.

Appl Bionics Biomech 2022 26;2022:6047074. Epub 2022 Jul 26.

Zigong Third People's Hospital, Sichuan 643000, China.

Objective: To investigate the safety and efficacy of single-pump and double-pump sequential anticoagulation in general hemodialysis under the condition of constant citrate.

Methods: A total of 32 patients with end-stage renal disease complicated with hemorrhage admitted by Zigong Third People's Hospital from December 2019 to December 2020 were collected. Randomly divided into single pump group ( = 17) and double pump group ( = 15). The coagulation of dialyzer and intravenous pot was compared between the two groups. Then, the changes of serum calcium before treatment, after 2 h treatment, and after the completion of the treatment, and the front of the blood pump and intravenous pot, as well as behind the intravenous pot were observed and recorded in the two groups. Then, single-pool clearance of urea/volume (spKt/V) was compared between the two groups.

Results: There were few differences in dialyzer coagulation between the single pump group and double pump group. However, the single pump group had a significant increase in the number of intravenous pot coagulations than the double pump group. At 2 h for dialysis, the serum calcium level behind the intravenous pot in the double pump group was notably lower than that in the single pump group. And after the completion of dialysis, the serum calcium returned to pretreatment level. The Kt/v in both groups reached the normal standard without statistically significant difference. And there were no adverse reactions in the patients of both groups after dialysis.

Conclusion: For hemodialysis patients with bleeding, dual-pump segmented anticoagulation is superior to single-pump anticoagulation in intravenous pot anticoagulation. Double pump segmented sequential constant citrate anticoagulation can be utilized as a new simple and effective anticoagulation method for clinical hemodialysis.
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http://dx.doi.org/10.1155/2022/6047074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345715PMC
July 2022

Deoxynivalenol induces caspase-3/GSDME-dependent pyroptosis and inflammation in mouse liver and HepaRG cells.

Arch Toxicol 2022 Aug 4. Epub 2022 Aug 4.

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, 510642, Guangdong, People's Republic of China.

Deoxynivalenol (DON), a frequent food and feed contaminant, poses a severe threat to human and livestock health. Some studies have demonstrated that DON could induce liver damage and cell death. However, novel cell death styles and detailed mechanisms to explain DON-induced liver inflammatory injury are still lacking. Here, we found both chronic and subacute oral administration of DON (3 mg/kg for 4 weeks and 4 mg/kg for 8 days) induced mouse liver inflammatory injury and activated caspase-3, PARP and gasdermin E (GSDME), which were inhibited by caspase-3 inhibitor Z-DEVD and Ac-DEVD. In vitro, HepaRG cells showed typical pyroptotic characteristics after 32 and 64 μM DON exposure for 24 h, including balloon-like bubbling emerging, release of lactate dehydrogenase (LDH), secretion of IL-1β and IL-6 and activation of caspase-3 and GSDME. Furthermore, knocking down GSDME and inhibiting caspases activity by Z-VAD and Z-DEVD dramatically blocked DON-induced pyroptotic characteristics, while over-expressed GSDME prompted that. These data demonstrate that caspase-3/GSDME pathway plays a key factor in DON-induced pyroptosis and inflammation in liver. Interestingly, knocking down GSDME could inhibit DON-induced pyroptosis but prompt DON-induced apoptosis, while opposite results were obtained when over-expressed GSDME, indicating the critical role of GSDME in DON-induced crosstalk between apoptosis and pyroptosis. Taken together, our data determine DON-induced caspase-3/GSDME-dependent pyroptosis in liver and its role in DON-induced liver inflammatory injury, which provide a novel mechanistic view into DON-induced hepatotoxicity and may offer a new target to reduce latent harm of DON to both humans and animals.
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http://dx.doi.org/10.1007/s00204-022-03344-9DOI Listing
August 2022

Morphometric Integrated Classification Index: A Multisite Model-Based, Interpretable, Shareable and Evolvable Biomarker for Schizophrenia.

Schizophr Bull 2022 Aug 4. Epub 2022 Aug 4.

Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China.

Background And Hypothesis: Multisite massive schizophrenia neuroimaging data sharing is becoming critical in understanding the pathophysiological mechanism and making an objective diagnosis of schizophrenia; it remains challenging to obtain a generalizable and interpretable, shareable, and evolvable neuroimaging biomarker for schizophrenia diagnosis.

Study Design: A Morphometric Integrated Classification Index (MICI) was proposed as a potential biomarker for schizophrenia diagnosis based on structural magnetic resonance imaging data of 1270 subjects from 10 sites (588 schizophrenia patients and 682 normal controls). An optimal XGBoost classifier plus sample-weighted SHapley Additive explanation algorithms were used to construct the MICI measure.

Study Results: The MICI measure achieved comparable performance with the sample-weighted ensembling model and merged model based on raw data (Delong test, P > 0.82) while outperformed the single-site models (Delong test, P < 0.05) in either the independent-sample testing datasets from the 9 sites or the independent-site dataset (generalizable). Besides, when new sites were embedded in, the performance of this measure was gradually increasing (evolvable). Finally, MICI was strongly associated with the severity of schizophrenia brain structural abnormality, with the patients' positive and negative symptoms, and with the brain expression profiles of schizophrenia risk genes (interpretable).

Conclusions: In summary, the proposed MICI biomarker may provide a simple and explainable way to support clinicians for objectively diagnosing schizophrenia. Finally, we developed an online model share platform to promote biomarker generalization and provide free individual prediction services (http://micc.tmu.edu.cn/mici/index.html).
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http://dx.doi.org/10.1093/schbul/sbac096DOI Listing
August 2022

Dermatofibrosarcoma protuberans presenting as an annulare cutaneous lesion: A case report.

Asian J Surg 2022 Jul 31. Epub 2022 Jul 31.

Department of Dermatology, GuiQian International General Hospital, No. 1, Dongfeng Street, Wudang District, Guiyang, Guizhou, 550018, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.07.013DOI Listing
July 2022

Lithium stabilizes square-two-dimensional metal sheets: a computational exploration.

Nanoscale 2022 Aug 3. Epub 2022 Aug 3.

School of Physical Science and Technology, Inner Mongolia University, Hohhot, 010021, China.

Based on the M-square-containing MLi (M = Al, Ga, In, Tl, Ge, Sn, Pb, Sb, Bi, Cu, Ag, Au, and Hg) clusters, we computationally designed two-dimensional (2D) MLi sheets consisting of M-square motifs. The four MLi-I (M = Sb, Bi, Ag, and Au) monolayers with Li square sublayer sandwiched between two M square sublayers (4/ space group) were confirmed to be stable (high cohesive energies, positive vibrational frequencies, moderate Young's moduli, and structural integrity during first-principles molecular dynamics simulations at 500 K), and the particle swarm optimization (PSO) method identified these constructed monolayers as the global minima in the 2D space. The three MLi-I (M = Sb, Bi, and Ag) monolayers demonstrated a half-auxetic behavior. AgLi-I could well activate CO and convert it into HCOOH by following the path * → *CO → *OCHO → *HCOOH → *+HCOOH. Particularly, AgLi-I shows great promise as an electrocatalyst for CO reduction as its limiting potential is as low as 0.40 (0.27) V without (with) considering the solvent effect. Our theoretical explorations reveal that lithium can stabilize the square metal monolayers, and the stable square binary metal sheets exhibit diverse mechanical and electrochemical properties, which can be used in the fields of mechanics and electrochemical catalysis.
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http://dx.doi.org/10.1039/d2nr02079cDOI Listing
August 2022

Enhanced biocrude production from hydrothermal conversion of municipal sewage sludge co-liquefaction with various model feedstocks.

RSC Adv 2022 Jul 13;12(31):20379-20386. Epub 2022 Jul 13.

Shenergy Environmental Technologies Co., Ltd Buiding 7. Vanka Canter, 988 Shenchang Rd Shanghai 201100 China

Hydrothermal co-liquefaction has the potential to improve biocrude yield. To investigate the influence of various types of biomass on co-liquefaction with municipal sewage sludge (MSS), experiments on MSS with three kinds of model feedstocks (soy oil, soy protein, and starch) were carried out. Reaction temperatures of 300, 320, and 340 °C proved to be the appropriate reaction temperatures for the highest biocrude yield for soy oil, soy protein, and starch, respectively. A synergistic effect on the biocrude yield of co-liquefaction was proved, and starch showed the highest synergistic effect with a 57.25% increase in biocrude yield, while soy oil only presented a slight synergistic effect. Thermal gravimetric analysis (TGA) results suggested that co-liquefaction with soy oil increased the light oil fractions in biocrude by 20.81%, but protein and starch led to more heavy oil fractions. Gas chromatography-mass spectrometry (GC-MS) indicated that co-liquefaction with protein or starch produced more cyclic compounds in the biocrude, while almost no new components appeared from co-liquefaction with soy oil.
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http://dx.doi.org/10.1039/d2ra02325cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277621PMC
July 2022

Non-coding RNAs in lung cancer: emerging regulators of angiogenesis.

J Transl Med 2022 08 2;20(1):349. Epub 2022 Aug 2.

Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Lung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.
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http://dx.doi.org/10.1186/s12967-022-03553-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344752PMC
August 2022

FedIPR: Ownership Verification for Federated Deep Neural Network Models.

IEEE Trans Pattern Anal Mach Intell 2022 Aug 2;PP. Epub 2022 Aug 2.

Federated learning models are collaboratively developed upon valuable training data owned by multiple parties. During the development and deployment of federated models, they are exposed to risks including illegal copying, re-distribution, misuse and/or free-riding. To address these risks, the ownership verification of federated learning models is a prerequisite that protects federated learning model intellectual property rights (IPR) i.e., FedIPR. We propose a novel federated deep neural network (FedDNN) ownership verification scheme that allows private watermarks to be embedded and verified to claim legitimate IPR of FedDNN models. In the proposed scheme, each client independently verifies the existence of the model watermarks and claims respective ownership of the federated model without disclosing neither private training data nor private watermark information. The effectiveness of embedded watermarks is theoretically justified by the rigorous analysis of conditions under which watermarks can be privately embedded and detected by multiple clients. Moreover, extensive experimental results on computer vision and natural language processing tasks demonstrate that varying bit-length watermarks can be embedded and reliably detected without compromising original model performances. Our watermarking scheme is also resilient to various federated training settings and robust against removal attacks.
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http://dx.doi.org/10.1109/TPAMI.2022.3195956DOI Listing
August 2022

Plasmonic Ag-decorated CuO nanowires for boosting photoelectrochemical CO reduction to multi-carbon products.

Chem Commun (Camb) 2022 Aug 2. Epub 2022 Aug 2.

School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China.

The generation of multi-carbon products on the CuO photocathode remains a great challenge. Herein, effective charge separation and surface catalytic reaction are achieved for photoelectrochemical CO reduction through plasmon metal (Ag) decoration on CuO nanowires. The CuO/Ag composite photocathode achieves a 47.7% faradaic efficiency for CHCOOH and the generation rate is 212.7 μmol cm h under illumination, which is about five times that in dark (44.4 μmol cm h) at -0.7 V RHE.
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http://dx.doi.org/10.1039/d2cc03167aDOI Listing
August 2022

Seeking Subjectivity in Visual Emotion Distribution Learning.

IEEE Trans Image Process 2022 4;31:5189-5202. Epub 2022 Aug 4.

Visual Emotion Analysis (VEA), which aims to predict people's emotions towards different visual stimuli, has become an attractive research topic recently. Rather than a single label classification task, it is more rational to regard VEA as a Label Distribution Learning (LDL) problem by voting from different individuals. Existing methods often predict visual emotion distribution in a unified network, neglecting the inherent subjectivity in its crowd voting process. In psychology, the Object-Appraisal-Emotion model has demonstrated that each individual's emotion is affected by his/her subjective appraisal, which is further formed by the affective memory. Inspired by this, we propose a novel Subjectivity Appraise-and-Match Network (SAMNet) to investigate the subjectivity in visual emotion distribution. To depict the diversity in crowd voting process, we first propose the Subjectivity Appraising with multiple branches, where each branch simulates the emotion evocation process of a specific individual. Specifically, we construct the affective memory with an attention-based mechanism to preserve each individual's unique emotional experience. A subjectivity loss is further proposed to guarantee the divergence between different individuals. Moreover, we propose the Subjectivity Matching with a matching loss, aiming at assigning unordered emotion labels to ordered individual predictions in a one-to-one correspondence with the Hungarian algorithm. Extensive experiments and comparisons are conducted on public visual emotion distribution datasets, and the results demonstrate that the proposed SAMNet consistently outperforms the state-of-the-art methods. Ablation study verifies the effectiveness of our method and visualization proves its interpretability.
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http://dx.doi.org/10.1109/TIP.2022.3193749DOI Listing
August 2022

Downregulated Dual-Specificity Protein Phosphatase 1 in Ovarian Carcinoma: A Comprehensive Study With Multiple Methods.

Pathol Oncol Res 2022 15;28:1610404. Epub 2022 Jul 15.

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

We aimed to explore the abnormal expression of dual-specificity protein phosphatase 1 (DUSP1) and its latent molecular mechanisms in ovarian carcinoma (OVCA). Two clinical cohorts collected from two different hospitals were used to evaluate the expression of DUSP1 protein in OVCA tissues. RNA-sequencing and microarray datasets were utilised to verify DUSP1 expression at mRNA levels in both OVCA tissues and in the peripheral blood of OVCA patients. Furthermore, an integrated calculation was performed to pool the standard mean difference (SMD) from each cohort in order to comprehensively assess the expression of DUSP1 in OVCA. Furthermore, we examined the relationship among DUSP1, tumour microenvironment (TME), and chemotherapy resistance in OVCA. Moreover, we used pathway enrichment analysis to explore the underlying mechanisms of DUSP1 in OVCA. A pooled SMD of -1.19 (95% CI [-2.00, -0.38], = 0.004) with 1,240 samples revealed that DUSP1 was downregulated in OVCA at both mRNA and protein levels. The area under the receiver operating characteristic curve of 0.9235 indicated the downregulated DUSP1 in peripheral blood may have a non-invasive diagnostic value in OVCA. Through six algorithms, we identified that DUSP1 may related to tumour-infiltrating T cells and cancer associated fibroblasts (CAFs) in OVCA. Pathway enrichment demonstrated that DUSP1 might participate in the mitogen-activated protein kinase (MAPK) signalling pathway. Furthermore, DUSP1 may have relations with chemotherapy resistance, and a favourable combining affinity was observed in the paclitaxel-DUSP1 docking model. DUSP1 was downregulated in OVCA, and this decreasing trend may affect the infiltration of CAFs. Finally, DUSP1 may have a targeting relation with paclitaxel and participate in MAPK signaling pathways.
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http://dx.doi.org/10.3389/pore.2022.1610404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336223PMC
August 2022

The Establishment of a Mouse Model for Degenerative Kyphoscoliosis Based on Senescence-Accelerated Mouse Prone 8.

Oxid Med Cell Longev 2022 20;2022:7378403. Epub 2022 Jul 20.

Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China.

Objective: Degenerative kyphoscoliosis (DKS) is a complex spinal deformity associated with degeneration of bones, muscles, discs, and facet joints. The aim of this study was to establish an animal model of degenerative scoliosis that recapitulates key pathological features of DKS and to validate the degenerative changes in senescence-accelerated mouse prone 8 (SAMP8) mice.

Methods: Thirty male mice were divided into 2 groups: 10 bipedal C57BL/6J mice were used as the control group, and 20 bipedal SAMP8 mice were used as the experimental group. Mice were bipedalized under general anesthesia. The incidence of scoliosis and bone quality was determined using radiographs and in vivo micro-CT images 4, 8, and 12 weeks after surgery, respectively. Histomorphological studies of muscle samples were performed after sacrifice at 12 weeks after surgery.

Results: On the 12th week, the incidence rates of kyphosis in C57BL/6J and SAMP8 groups were 50% and 100%, respectively. Overall, the incidence and angle of kyphosis were significantly higher in the bipedal SAMP8 group compared to the C57BL/6J group (44.7°± 6.2° vs. 84.3°± 10.3°, P<0.001). Based on 3D reconstruction of the entire spine, degeneration of the intervertebral disc was observed in bipedal SAMP8 mice, including the reduction of disc height and the formation of vertebral osteophytes. The bone volume ratio (BV/TV) was significantly suppressed in the bipedal SAMP8 group compared with the bipedal C57BL/6J group. In addition, HE staining and Mason staining of the paraspinal muscle tissue showed chronic inflammation and fibrosis in the muscles of the bipedal SAMP8 group.

Conclusions: The SAMP8 mouse model can be taken as a clinically relevant model of DKS, and accelerated aging of the musculoskeletal system promotes the development of kyphosis.
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http://dx.doi.org/10.1155/2022/7378403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329026PMC
August 2022
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