Publications by authors named "Xiaoyan Wu"

596 Publications

Effect of nickel (II) on the performance of anodic electroactive biofilms in bioelectrochemical systems.

Water Res 2022 Jul 22;222:118889. Epub 2022 Jul 22.

School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China; Key Laboratory of Biometallurgy, Ministry of Education, Changsha 410083, China. Electronic address:

The impact of nickel (Ni) on the performance of anodic electroactive biofilms (EABs) in the bioelectrochemical system (BES) was investigated in this study. Although it has been reported that Ni influences microorganisms in a number of ways, it is unknown how its presence in the anode of a BES affects extracellular electron transfer (EET) of EABs, microbial viability, and the bacterial community. Results revealed that the addition of Ni decreased power output from 673.24 ± 12.40 mW/m at 0 mg/L to 179.26 ± 9.05 mW/m at 80 mg/L. The metal and chemical oxygen demand removal efficiencies of the microbial fuel cells (MFCs) declined as Ni concentration increased, which could be attributed to decreased microbial viability as revealed by SEM and CLSM. FTIR analysis revealed the involvement of various microbial biofilm functional groups, including hydroxyl, amides, methyl, amine, and carboxyl, in the uptake of Ni. The presence of Ni on the anodic biofilms was confirmed by SEM-EDS and XPS analyses. CV demonstrated that the electron transfer performance of the anodic biofilms was negatively correlated with the various Ni concentrations. EIS showed that the internal resistance of the MFCs increased with increasing Ni concentration, resulting in a decrease in power output. High-throughput sequencing results revealed a decrease in Geobacter and an increase in Desulfovibrio in response to Ni concentrations of 10, 20, 40, and 80 mg/L. Furthermore, the various Ni concentrations decreased the expression of EET-related genes. The Ni-fed MFCs had a higher abundance of the nikR gene than the control group, which was important for Ni resistance. This work advances our understanding of Ni inhibition on EABs, as well as the concurrent removal of organic matter and Ni from wastewater.
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http://dx.doi.org/10.1016/j.watres.2022.118889DOI Listing
July 2022

LuxR family transcriptional repressor YjjQ modulates the biofilm formation and motility of avian pathogenic Escherichia coli.

Res Vet Sci 2022 Jul 22;152:10-19. Epub 2022 Jul 22.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, PR China. Electronic address:

Avian pathogenic Escherichia coli (APEC) can cause the acute and sudden death of poultry, which leads to serious economic losses in the poultry industry. Biofilm formation contributes to the persistence of bacterial infection, drug resistance, and resistance to diverse environmental stress. Many transcription regulators in APEC play an essential role in the formation of biofilm and could provide further insights into APEC pathogenesis. YjjQ has an important role in the pathogenicity of bacteria by regulating the expression of virulence factors, such as flagellar and iron uptake. However, YjjQ regulates other virulence factors, and their role in the overall regulatory network is unclear. Here, we further evaluate the function of YjjQ on APEC biofilm formation and motility. In this study, we successfully constructed mutant (AE27∆yjjQ) and complement (AE27ΔyjjQ-comp) strains of the wild-type strain AE27. Inactivation of the yjjQ gene significantly increased biofilm-forming ability in APEC. Scanning electron microscopy showed that the biofilm formation of the AE27 was single-layered and flat, whereas that of the AE27∆yjjQ had a porous three-dimensional structure. Moreover, the deletion of the yjjQ gene inhibited the motility of APEC. RNA-sequencing was used to further investigate the regulatory mechanism of YjjQ in APEC. The results indicate that YjjQ regulates biofilm formation and flagellar genes in AE27∆yjjQ. RT-qPCR shows that YjjQ affects the transcriptional levels of genes, including flagella genes (flhD, flhC and flgE), and biofilm formation genes (pstA, uhpC, nikD, and ygcS). These results confirm that the transcription regulator YjjQ is involved in APEC biofilm formation and motility, and provide new evidence for the prevention and control of APEC.
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http://dx.doi.org/10.1016/j.rvsc.2022.07.011DOI Listing
July 2022

LuxR family transcriptional repressor YjjQ modulates the biofilm formation and motility of avian pathogenic Escherichia coli.

Res Vet Sci 2022 Jul 22;152:10-19. Epub 2022 Jul 22.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, PR China. Electronic address:

Avian pathogenic Escherichia coli (APEC) can cause the acute and sudden death of poultry, which leads to serious economic losses in the poultry industry. Biofilm formation contributes to the persistence of bacterial infection, drug resistance, and resistance to diverse environmental stress. Many transcription regulators in APEC play an essential role in the formation of biofilm and could provide further insights into APEC pathogenesis. YjjQ has an important role in the pathogenicity of bacteria by regulating the expression of virulence factors, such as flagellar and iron uptake. However, YjjQ regulates other virulence factors, and their role in the overall regulatory network is unclear. Here, we further evaluate the function of YjjQ on APEC biofilm formation and motility. In this study, we successfully constructed mutant (AE27∆yjjQ) and complement (AE27ΔyjjQ-comp) strains of the wild-type strain AE27. Inactivation of the yjjQ gene significantly increased biofilm-forming ability in APEC. Scanning electron microscopy showed that the biofilm formation of the AE27 was single-layered and flat, whereas that of the AE27∆yjjQ had a porous three-dimensional structure. Moreover, the deletion of the yjjQ gene inhibited the motility of APEC. RNA-sequencing was used to further investigate the regulatory mechanism of YjjQ in APEC. The results indicate that YjjQ regulates biofilm formation and flagellar genes in AE27∆yjjQ. RT-qPCR shows that YjjQ affects the transcriptional levels of genes, including flagella genes (flhD, flhC and flgE), and biofilm formation genes (pstA, uhpC, nikD, and ygcS). These results confirm that the transcription regulator YjjQ is involved in APEC biofilm formation and motility, and provide new evidence for the prevention and control of APEC.
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http://dx.doi.org/10.1016/j.rvsc.2022.07.011DOI Listing
July 2022

Collateral-Core Ratio as a Novel Predictor of Clinical Outcomes in Acute Ischemic Stroke.

Transl Stroke Res 2022 Jul 25. Epub 2022 Jul 25.

Department of Radiology, Chinese PLA General Hospital/Chinese PLA Medical School, 28 Fuxing Road, Beijing, 100853, China.

The interaction effect between collateral circulation and ischemic core size on stroke outcomes has been highlighted in acute ischemic stroke (AIS). However, biomarkers that assess the magnitude of this interaction are still lacking. We aimed to present a new imaging marker, the collateral-core ratio (CCR), to quantify the interaction effect between these factors and evaluate its ability to predict functional outcomes using machine learning (ML) in AIS. Patients with AIS caused by anterior circulation large vessel occlusion (LVO) were recruited from a prospective multicenter study. CCR was calculated as collateral perfusion volume/ischemic core volume. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. An ML model was built and tested with a tenfold cross-validation using nine clinical and four imaging variables with mRS score 3-6 as unfavorable outcomes. Among 129 patients, CCR was identified as the most important variable. The prediction model incorporating clinical factors, ischemic core volume, collateral perfusion volume, and CCR showed better discriminatory power in predicting unfavorable outcomes than the model without CCR (mean C index 0.853 ± 0.108 versus 0.793 ± 0.133, P = 0.70; mean net reclassification index 52.7% ± 32.7%, P < 0.05). When patients were divided into two groups based on their CCR value with a threshold of 0.73, unfavorable outcomes were significantly more prevalent in patients with CCR ≤ 0.73 than in those with CCR > 0.73. CCR is a robust predictor of functional outcomes, as identified by ML, in patients with acute LVO. The prediction model that incorporated CCR improved the model's ability to identify unfavorable outcomes. ClinicalTrials.gov Identifier: NCT02580097.
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http://dx.doi.org/10.1007/s12975-022-01066-9DOI Listing
July 2022

Methanol biotransformation toward high-level production of fatty acid derivatives by engineering the industrial yeast .

Proc Natl Acad Sci U S A 2022 Jul 11;119(29):e2201711119. Epub 2022 Jul 11.

Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Methanol-based biorefinery is a promising strategy to achieve carbon neutrality goals by linking CO capture and solar energy storage. As a typical methylotroph, shows great potential in methanol biotransformation. However, challenges still remain in engineering methanol metabolism for chemical overproduction. Here, we present the global rewiring of the central metabolism for efficient production of free fatty acids (FFAs; 23.4 g/L) from methanol, with an enhanced supply of precursors and cofactors, as well as decreased accumulation of formaldehyde. Finally, metabolic transforming of the fatty acid cell factory enabled overproduction of fatty alcohols (2.0 g/L) from methanol. This study demonstrated that global metabolic rewiring released the great potential of for methanol biotransformation toward chemical overproduction.
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http://dx.doi.org/10.1073/pnas.2201711119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303929PMC
July 2022

Arterial Spin Labeling-Based MRI Estimation of Penumbral Tissue in Acute Ischemic Stroke.

J Magn Reson Imaging 2022 Jul 18. Epub 2022 Jul 18.

Department of Radiology, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, China.

Background: Arterial spin labeling (ASL) has shown potential for the assessment of penumbral tissue in patients with acute ischemic stroke (AIS). The postlabeling delay (PLD) parameter is sensitive to arterial transit delays and influences cerebral blood flow measurements.

Purpose: To assess the impact of ASL acquisition at different PLDs for penumbral tissue quantification and to compare their performance regarding assisting patient selection for endovascular treatment with dynamic susceptibility contrast MRI (DSC-MRI) as the reference method.

Study Type: Retrospective.

Population: A total of 53 patients (59.98 ± 12.60 years, 32% women) with AIS caused by internal carotid or middle cerebral artery occlusion.

Field Strength/sequence: A 3-T, three-dimensional pseudo-continuous ASL with fast-spin echo readout.

Assessment: Hypoperfusion volume was measured using DSC-MRI and ASL with PLDs of 1.500 msec and 2.500 msec, respectively. Eligibility for endovascular treatment was retrospectively determined according to the imaging criteria of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial (DEFUSE 3).

Statistical Tests: Kruskal-Wallis tests, Bland-Altman plots, Cohen's kappa, and receiver operating characteristic analyses were used. The threshold for statistical significance was set at P ˂ 0.05.

Results: Hypoperfusion volume for ASL with a PLD of 1.500 msec was significantly larger than that for DSC-MRI, while the hypoperfusion volume for a PLD of 2.500 msec was not significantly different from that of DSC-MRI (P = 0.435). Bland-Altman plots showed that the mean volumetric error between the hypoperfusion volume measured by DSC-MRI and ASL with PLDs of 1.500/2.500 msec was -107.0 mL vs. 4.49 mL. Cohen's kappa was 0.679 vs. 0.773 for DSC-MRI and ASL, respectively, with a PLD of 1.500/2.500 msec. The sensitivity and specificity for ASL with a PLD of 1.500/2.500 msec in identifying patients eligible for treatment were 89.74% vs. 97.44% and 92.86% vs. 64.29%, respectively.

Data Conclusion: In AIS, PLDs for ASL acquisition may have a considerable impact on the quantification of the hypoperfusion volume.

Evidence Level: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.28364DOI Listing
July 2022

Case Report: Extracorporeal Membrane Oxygenation Followed by Intra-Aortic Balloon Counterpulsation Successfully Treated Cardiac Arrest Caused by Anomalous Origin of a Left Coronary Artery From the Right Coronary Sinus.

Front Med (Lausanne) 2022 29;9:936721. Epub 2022 Jun 29.

Department of Intensive Care Medicine, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China.

Background: Anomalous origin of a coronary artery (AOCA) is defined as the failure of the coronary artery to originate from the normal coronary sinus. The anomalous origin of the left coronary artery arising from the right coronary sinus is rare, dangerous and at risk of malignant arrhythmia, sudden death, and high mortality.

Case Presentation: In this study, we present a 14-year-old adolescent male who went to a hospital with transient unconsciousness after exercise, who subsequently developed cardio arrest due to malignant arrhythmia. He was admitted to the intensive care unit, and who subsequently received successful veno-arterial extracorporeal membrane oxygenation (VA ECMO) assisted circulation followed by intra-aortic balloon counterpulsation (IABP). Echocardiography and cardiac CTA were also performed, further confirming that the abnormal left coronary artery originated from the right coronary sinus. The patient subsequently underwent heart surgery.

Conclusion: The successful treatment of the patient in this report was attributed to the immediately VA ECMO, supplemented by IABP. Establishing clear diagnosis is a process of multidisciplinary joint diagnosis, which provides a reference for clinicians when encountering similar cases.
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http://dx.doi.org/10.3389/fmed.2022.936721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276961PMC
June 2022

Dose-Response Association of Low and Normal Ankle Brachial Index With the Risk of Cardiovascular Disease Morbidity and Mortality.

Angiology 2022 Jul 13:33197221114701. Epub 2022 Jul 13.

Department of Epidemiology and Biostatistics, College of Public Health, 12636Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

We quantitatively evaluated the dose-response association of low and normal ankle brachial index (ABI) with the risk of morbidity and mortality from cardiovascular diseases (CVDs). PubMed, Embase, and Web of Science were systematically searched for cohort studies. Random effects or fixed effects models were used to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to assess study-specific dose-response associations per 0.1 ABI decrease. Restricted cubic splines were used to evaluate linear or nonlinear trends. Twelve cohort studies (57 031 participants) were included in this meta-analysis. For low vs normal ABI levels, the pooled RRs were 2.03 (95% CI, 1.72-2.41; = 52.9%; p=0.030) and 2.29 (95% CI, 1.98-2.64; = 39.5%; p =0.158) for CVD morbidity and CVD mortality, respectively. For per 0.1 ABI decrease from 1.40 the risk for CVD morbidity and CVD mortality increased by 8% (1.08, 95% CI 1.04-1.11) and 11% (1.11, 95% CI 1.07-1.15), respectively. Restricted cubic splines showed inverse linear associations for CVD morbidity and CVD mortality. As a non-invasive index, lower ABI was significantly associated with the increased risk of morbidity and mortality from CVDs in an inverse linear manner.
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http://dx.doi.org/10.1177/00033197221114701DOI Listing
July 2022

Qishen Yiqi dropping pills improve isoproterenol-induced cardiomyocyte hypertrophy by regulating X-inactive specific transcript (XIST) expression in rats.

J Thorac Dis 2022 Jun;14(6):2213-2223

Department of Cardiology, the Second Affiliated Hospital of Hainan Medical College, Haikou, China.

Background: This study aimed to explore the potential mechanism of Qishen Yiqi dropping pills (QYDPs) in the treatment of chronic heart failure (CHF) by regulating the expression of lncRNAs during CHF.

Methods: Differences in the expression of the long non-coding RNA (lncRNA), X-inactive specific transcript (XIST), in an isoproterenol (ISO)-induced cardiomyocyte hypertrophy model treated with QYDPs was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). A cell counting kit-8 (CCK8) assay, flow cytometry (FCM), and enzyme linked immunosorbent assay (ELISA) were used to analyze the protective effects of QYDPs on the proliferation rate, apoptosis, myocardial enzyme, oxidative stress, and inflammation of cardiomyocytes, as well as the molecular mechanism of XIST.

Results: Our results showed that in the ISO-induced cardiomyocyte hypertrophy model, XIST expression and apoptosis were increased, the cell proliferation rate was decreased, and myocardial enzyme levels increased [i.e., increased lactate dehydrogenase (LDH) and creatine kinase (CK) levels]. Furthermore, cellular oxidative stress [i.e., increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) levels] and inflammatory response [i.e., increased interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α protein secretion] were also promoted. QYDP treatment effectively mitigated the effects of ISO induction. Subsequently, we found that suppressing XIST expression reversed the effect of ISO induction, whereas overexpression (ov) of XIST enhanced the effect of ISO induction. Finally, this study confirmed that QYDP treatment improved the ISO-induced decrease in proliferation, apoptosis, and promotion of oxidative stress and inflammatory response in cardiomyocytes, whereas ov of XIST partially negated the effect of QYDPs.

Conclusions: QYDPs protected H9c2 cells from ISO-induced damage by downregulating XIST expression.
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http://dx.doi.org/10.21037/jtd-22-606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264057PMC
June 2022

Slc6a13 Deficiency Attenuates Pasteurella multocida Infection-Induced Inflammation via Glycine-Inflammasome Signaling.

J Innate Immun 2022 Jul 7:1-15. Epub 2022 Jul 7.

College of Veterinary Medicine, Southwest University, Chongqing, China.

We have previously demonstrated that Slc6a13-deficient (Slc6a13-/-; KO) mice are resistant to P. multocida infection, which might be in connection with macrophage-mediated inflammation; however, the specific metabolic mechanism is still enigmatic. Here we reproduce the less sensitive to P. multocida infection in overall survival assays as well as reduced bacterial loads, tissue lesions, and inflammation of lungs in KO mice. The transcriptome sequencing analysis of wild-type (WT) and KO mice shows a large number of differentially expressed genes that are enriched in amino acid metabolism by functional analysis. Of note, glycine levels are substantially increased in the lungs of KO mice with or without P. multocida infection in comparison to the WT controls. Interestingly, exogenous glycine supplementation alleviates P. multocida infection-induced inflammation. Mechanistically, glycine reduces the production of inflammatory cytokines in macrophages by blocking the activation of inflammasome (NALP1, NLRP3, NLRC4, AIM2, and Caspase-1). Together, Slc6a13 deficiency attenuates P. multocida infection through lessening the excessive inflammatory responses of macrophages involving glycine-inflammasome signaling.
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http://dx.doi.org/10.1159/000525089DOI Listing
July 2022

8-Oxypalmatine, a novel oxidative metabolite of palmatine, exhibits superior anti-colitis effect via regulating Nrf2 and NLRP3 inflammasome.

Biomed Pharmacother 2022 Jun 29;153:113335. Epub 2022 Jun 29.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, PR China. Electronic address:

Palmatine (PAL) is an isoquinoline alkaloid derived from Fibraureae caulis Pierre that has been used to relieve inflammatory diseases like ulcerative colitis (UC). The metabolites of PAL were believed to contribute significantly to its outstanding biological activities. 8-Oxypalmatine (OPAL), a liver-mediated oxidative metabolite of PAL, has been firstly identified in the present work. We aimed to comparatively investigate the potential effect and mechanism of OPAL and PAL on dextran sodium sulfate (DSS)-induced colitis in Balb/c mice. Results indicated that OPAL and PAL effectively mitigated clinical manifestations, DAI scores and pathological damage compared with the model group. Moreover, treatment with OPAL and PAL effectively mitigated oxidative stress markers and inflammatory mediators in colon. Additionally, OPAL and PAL significantly activated the Nrf2 pathway, while substantially suppressed the activation of NLRP3 inflammasome. Furthermore, OPAL showed superior anti-colitis effect to PAL, which was similar to the positive drug mesalazine with much smaller dosage. These findings suggested that OPAL exerted appreciable protective effect on DSS-induced colitis, at least in part, via activating Nrf2 pathway and inhibiting NLRP3 inflammasome. OPAL might have the potential to be further developed into a promising candidate for the treatment of UC.
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http://dx.doi.org/10.1016/j.biopha.2022.113335DOI Listing
June 2022

Protective cellular and humoral immune responses to Edwardsiella tarda in flounder (Paralichthys olivaceus) immunized by an inactivated vaccine.

Mol Immunol 2022 Jun 28;149:77-86. Epub 2022 Jun 28.

Laboratory of Pathology and Immunology of Aquatic Animals, KLMME, Ocean University of China, Qingdao 266003, PR China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, No. 1 Wenhai Road,Aoshanwei Town, Qingdao, PR China.

Protection is crucial for a vaccine. In this study, flounder was inoculated with an inactivated Edwardsiella tarda for 5 weeks then challenged with E. tarda, after that, the protective cellular and humoral immune responses were studied using specific antibodies against CD4, CD8 and IgM, respectively, previously produced in our lab. And then gene transcription, relative percent survival (RPS), innate enzyme activities and histopathology were investigated. The results showed that, in the vaccine group, the percentage of CD4 T and CD8 T lymphocytes increased significantly, peaking on 7th post challenge day. The percentage of IgM B lymphocytes increased significantly first and peaked at 2nd post challenge week. Total and specific antibodies significantly increased and peaked at 3rd week. The mRNA expressions of MHCIα, MHCIIα, CD4-1 and CD8α were significantly upregulated. In the meantime, alkaline phosphatase, acid phosphatase, superoxide dismutase and lysozyme significantly rose and reached to the maximum. The RPS was 54.76 ± 1.92%. The bacterial load in spleen and head kidney was lower in the vaccine group than that of PBS group. These data illustrated that T lymphocyte subsets, B lymphocytes, immune enzymes were induced strong protection against E. tarda for flounder. These results revealed a strong support protection of the vaccine from four aspects, and provided a new perspective for the evaluation of fish vaccines.
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http://dx.doi.org/10.1016/j.molimm.2022.06.008DOI Listing
June 2022

Association between trajectories of problematic mobile phone use and chronotype among Chinese college students.

Addict Behav 2022 Jun 9;134:107398. Epub 2022 Jun 9.

Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, China. Electronic address:

Aims: This study aimed to describe the prevalence of problematic mobile phone use (PMPU) and chronotype among Chinese college students, estimate PMPU development trajectories, and further examine the effect of PMPU trajectories on chronotype.

Design: In a stratified cluster sampling design, PMPU and chronotype were evaluated in 999 college students from two universities in a 2-year prospective investigation from April 2019 to April 2021, and an investigation was conducted every six months (time 1 ∼ time 5, T1 ∼ T5).

Participants: N = 999 college students (mean age at T1: 18.8 years (SD = 1.2), 37.7% male) took part in the study.

Measurements: The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and the Pittsburgh Sleep Quality Index (PSQI) were used to assess the PMPU and sleep quality of college students at each time point. The Morning and Evening Questionnaire (MEQ) was adopted to investigate the chronotype of college students at T5.

Findings: The prevalence of PMPU at T1 ∼ T5 was 24.3%, 27.3%, 35.1%, 31.2% and 31.9%, respectively. The prevalence rates of morning types (M-types), neutral types (N-types), and evening types (E-types) were 19.1%, 70.8%, and 10.1%, respectively. Using latent growth mixture modelling, we identified three trajectories of PMPU: low-level (49.5%), moderate-level (38.6%), and high-level score trajectories (11.9%). Multivariate logistic regression analysis results showed that a trajectory with a high score was positively associated with E-types (P < 0.05). After stratification by gender, a high-level score trajectory was positively associated with E-types only among female college students (P < 0.05). There were sex differences in the association between trajectories of PMPU and chronotype.

Conclusion: Long-term symptoms of PMPU may be a potential risk factor for circadian rhythm disturbance among college students, and this effect was significantly different between genders.
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http://dx.doi.org/10.1016/j.addbeh.2022.107398DOI Listing
June 2022

Insight into the microbial mechanisms for the improvement of composting efficiency driven by Aneurinibacillus sp. LD3.

Bioresour Technol 2022 Sep 17;359:127487. Epub 2022 Jun 17.

School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China; Key Laboratory of Biometallurgy, Ministry of Education, Changsha 410083, China. Electronic address:

This work explored the microbial mechanisms for the improvement of composting efficiency driven by thermotolerant lignin-degrading bacterium Aneurinibacillus sp. LD3 (LD3). Results showed that LD3 inoculant prolonged the thermophilic period by 4 days, improved the final content of humic acid, total phosphorus (TP), nitrogen, potassium and seed germination index. Inoculating LD3 enhanced the relative abundance of thermotolerant and phosphate-solubilizing microbes including the phyla of Proteobacteria, Bacteroidota, Firmicutes, and Actinobacteriota, and the genus of Bacillus, Thermoactinomyces, and Pseudomonas. Metabolic function analysis showed that sequences involved in carbohydrate and amino acid metabolism were boosted, while sequences associated with human disease were reduced after inoculating LD3. Spearman correlation analysis revealed that Aneurinibacillus has a significant positive correlation with temperature, TP, Bacillus, and Thermoactinomyces. This study provides useful information for understanding the microbial mechanisms of LD3 promoting composting efficiency, and reveals the tremendous potential of LD3 in the resource utilization of organic solid wastes.
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http://dx.doi.org/10.1016/j.biortech.2022.127487DOI Listing
September 2022

Comparison of Nonalbuminuric and Albuminuric Diabetic Kidney Disease Among Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2022 3;13:871272. Epub 2022 Jun 3.

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

Background: Diabetic kidney disease (DKD) is one of most common complications of diabetes. Recently, the classical phenotype of DKD, which is characterized by albuminuria preceding renal insufficiency, has been challenged since a subset of diabetic patients with renal insufficiency but without albuminuria has been increasingly reported. However, the available evidence is inconsistent. Thus, the present systematic review will assess and summarize the available data regarding nonalbuminuric diabetic kidney disease (NADKD).

Methods: PubMed, Embase, and Cochrane were searched for clinical trials related to NADKD. The results were limited to full-text articles published in English, without restrictions on the publication time. The quality of clinical trials was appraised, and the data were extracted. Meta-analysis was conducted using a random-effects model. Descriptive analysis was performed if the data were insufficient.

Results: A final total of 31 articles were included in this review. The meta-analysis of 18 studies showed that compared with albuminuric DKD, patients with NADKD were older ( = 1.04 years old, 95% CI [0.52, 1.57], < 0.05); were more often women (Male = 0.74, 95% CI [0.68, 0.81], < 0.05); had shorter diabetes duration ( = 2.9 years, 95% CI [-3.63, -2.18], < 0.05), lower HbA1c levels ( = 0.34%, 95% CI [-0.42, -0.25], < 0.05), and lower blood pressure (systolic blood pressure = 6.21 mmHg, 95% CI [-9.41, -3.0], < 0.05; diastolic blood pressure = 1.27 mmHg, 95% CI [-2.15, 4.0], < 0.05); less frequently experienced diabetic retinopathy ( = 0.58, 95% CI [0.51, 0.67], < 0.05); and less frequently used renin-angiotensin-aldosterone system (RAAS) inhibitors. The underlying pathology of NADKD might be different from that of the classic phenotype of DKD, which is associated with more advanced tubulointerstitial and vascular lesions but mild typical glomerular lesions. The annual estimated glomerular filtration rate decline tended to be lower in patients with NADKD than in those with albuminuric DKD. The risk for cardiovascular disease, end-stage renal disease, and all-cause death was lower for patients with NADKD than patients with albuminuric DKD.

Conclusions: The prevalence of NADKD has increased in recent decades, and its characteristics, pathology, and prognosis are different from those of albuminuric DKD; thus, diagnosis and treatment strategies should be different. More attention should be given to this phenotype.
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http://dx.doi.org/10.3389/fendo.2022.871272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203723PMC
June 2022

[Mediating role of IL-10 in the association between health-risk behaviors and depressive symptoms of college students].

Wei Sheng Yan Jiu 2022 May;51(3):353-360

School of Public Health, Anhui Medical University, Hefei 230032, China MOE Key Laboratory of Population Health Across Life Cycle/NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China.

Objective: To examine the relationship between health-risk behaviors and depressive symptoms among college students, and explore the mediating role of plasma IL-10 level in the relationship between the two.

Methods: Freshman students in two universities in Hefei City, Anhui Province and Shangrao City, Jiangxi Province were recruited between April and May 2019, and follow-up investigation was conducted 6 months later. Health risk behaviors were measured based on the Young Risk Behavior Surveillance System(YRBSS) questionnaire, and depressive symptoms was evaluated by using the Depression Anxiety Stress Scale(DASS-21) among college students at baseline and 6 months follow-up survey. Plasma interleukin-10(IL-10) level was measured at baseline. Univariate analysis was used to compare the correlation between health risk behaviors and depressive symptoms among college students. Binary Logistic regression analyzed the relationship between health risk behaviors, IL-10 and depressive symptoms. The mediation model was used to explore the mediating role of IL-10 levels in the association between health risk behaviors and depressive symptoms.

Results: At baseline, boys reported a higher rate of depressive symptoms than that of girls(χ~2=6.33, P=0.01); higher rates of depressive symptoms were observed in students who were from a family with a low perceived economic status(χ~2=7.31, P=0.03)or in poor health(χ~2=6.71, P=0.04). Participants who reported low physical activity(χ~2=19.09, P<0.01), smoking(χ~2=7.03, P<0.01), and poor sleep quality(χ~2=68.78, P<0.01)at baseline were more likely to experience depressive symptoms. Multiple health-risk behaviors at baseline were positively correlated with depressive symptoms among college students. After adjusting gender, self-reported family economy and self-rated health, the regression model showed that plasma IL-10 at baseline was negatively associated with the prevalence of depressive symptoms(OR=0.36, 95% CI 0.18-0.72) and the incidence of depressive symptoms after 6 months(OR=0.20, 95% CI 0.08-0.49). Structural equation model showed that health-risk behaviors was negatively correlated to IL-10 level(β=-0.13, SE=0.04), IL-10 negatively predicted depressive symptoms at follow-up(β=-0.09, SE=0.04), and IL-10 play a mediating role between health risk behavior and depressive symptoms.

Conclusion: Health risk behaviors are positively correlated with depressive symptoms among college students. Plasma IL-10 level at baseline was negatively associated with the incidence of depressive symptoms after 6 months, and IL-10 level at baseline has a partial mediating effect between baseline health risk behavior clustering and depressive symptoms at follow-up.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2022.03.002DOI Listing
May 2022

Pearl-inspired graphene oxide-collagen microgel with multi-layer mineralization through microarray chips for bone defect repair.

Mater Today Bio 2022 Jun 30;15:100307. Epub 2022 May 30.

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

Biomineralization of natural polymers in simulated body fluid (SBF) can significantly improve its biocompatibility, osteoconductivity, and osteoinductivity because of the hydroxyapatite (HAp) deposition. Nevertheless, the superficial HAp crystal deposition hamper the deep inorganic ions exchange in porous microgels, thus gradually leading to a nonuniform regeneration effect. Inspired by the pearl forming process, this article uses the microarray chips to fabricate the multi-layer mineralized graphene oxide (GO)-collagen (Col)-hydroxyapatite (HAp) microgel, denoted as MMGCH. These fabricated MMGCH microgels exhibit porous structure and uniform HAp distribution. Furthermore, the suitable microenvironment offered by microgel promotes the time-dependent proliferation and osteogenic differentiation of stem cells, which resulted in upregulated osteogenesis-related genes and proteins, such as alkaline phosphatase, osteocalcin, and collagen-1. Finally, the MMGCH microgels possess favorable bone regeneration capacities both in cranial bone defects and mandibular bone defects via providing a suitable microenvironment for host-derived cells to form new bone tissues. This work presents a biomimetic means aiming to achieve full-thickness and uniform HAp deposition in hydrogel for bone defect repair.
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http://dx.doi.org/10.1016/j.mtbio.2022.100307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189211PMC
June 2022

Nutrient sensing, signaling transduction, and autophagy in podocyte injury: implications for kidney disease.

J Nephrol 2022 Jun 15. Epub 2022 Jun 15.

Division of Nephrology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430070, Hubei, China.

Podocytes are terminally differentiated epithelial cells of the renal glomerular tuft and these highly specialized cells are essential for the integrity of the slit diaphragm. The biological function of podocytes is primarily based on a complex ramified structure that requires sufficient nutrients and a large supply of energy in support of their unique structure and function in the glomeruli. Of note, the dysregulation of nutrient signaling and energy metabolic pathways in podocytes has been associated with a range of kidney diseases i.e., diabetic nephropathy. Therefore, nutrient-related and energy metabolic signaling pathways are critical to maintaining podocyte homeostasis and the pathogenesis of podocyte injury. Recently, a growing body of evidence has indicated that nutrient starvation induces autophagy, which suggests crosstalk between nutritional signaling with the modulation of autophagy for podocytes to adapt to nutrient deprivation. In this review, the current knowledge and advancement in the understanding of nutrient sensing, signaling, and autophagy in the podocyte biology, injury, and pathogenesis of kidney diseases is summarized. Based on the existing findings, the implications and perspective to target these signaling pathways and autophagy in podocytes during the development of novel preventive and therapeutic strategies in patients with podocyte injury-associated kidney diseases are discussed.
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http://dx.doi.org/10.1007/s40620-022-01365-2DOI Listing
June 2022

Oxyberberine, a novel HO-1 agonist, effectively ameliorates oxidative stress and inflammatory response in LPS/D-GalN induced acute liver injury mice via coactivating erythrocyte metabolism and Nrf2 signaling pathway.

Food Chem Toxicol 2022 Aug 9;166:113215. Epub 2022 Jun 9.

College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510630, PR China. Electronic address:

Oxyberberine (OBB), a main gut-mediated metabolite of Phellodendron chinense Cortex (PC), exhibits prominent protective property against acute liver injury (ALI). Heme oxygenase-1 (HO-1) is a vital molecule in attenuating acute and chronic liver injury for its prominent anti-oxidative injury and anti-inflammation properties. The present study was performed to investigate the hepatoprotective role of OBB through HO-1 signaling pathway in lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced ALI. Our results indicated that PC treatment improved survival rate and its metabolite OBB evidently improved histopathological deteriorations and liver function. Additionally, OBB dramatically ameliorated hepatic oxidative stress and inflammation. Besides, OBB exerted remarkable HO-1 agonistic activity, even be comparable to hemin (a HO-1 inducer), as evidenced by increased HO-1 level, carbon monoxide and bilirubin activities, which are the markers of erythrocyte metabolism. Moreover, OBB modulated the parameters of inflammation and oxidative stress through HO-1 dependent pathway. Beyond this, OBB also notably suppressed the translocation of p65, enhanced antioxidation defense genes expressions, promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2). In conclusion, OBB could be the principle active metabolite substance of PC and exert excellent hepatoprotective effects via inducing HO-1 through coactivation of erythrocyte metabolism and Nrf2/HO-1 pathway.
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http://dx.doi.org/10.1016/j.fct.2022.113215DOI Listing
August 2022

Patients' Responses to COVID-19 Pandemic: The Relationship Between Potential Pandemic-Induced Disruptions, Ontological Security, and Adaptive Responses in Taizhou, China.

Front Public Health 2022 19;10:865046. Epub 2022 May 19.

Evidence-Based Medicine Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, China.

Background: The COVID-19 pandemic has changed the social environment of most individuals around the world and has profoundly impacted people's lives, ontological security, and behavior. Among them, the patients are one of the groups most influenced by the pandemic.

Objective: The present research aimed to study the relationship of COVID-19 pandemic-induced disruption to patients' daily lives, ontological security, and patients' responses to prevent the spread of COVID-19, and explore the role of ontological security.

Methods: This article was based on an online structured questionnaire study conducted among hospitalized patients in Taizhou Hospital of Zhejiang Province, Taizhou, China, from 8 July to 11 August 2021. We analyzed the data using the multivariate regression model and mediation analysis method.

Results: The results showed that the higher the pandemic-induced disruption to inpatients' lives, the better behavior would be taken by hospitalized patients to prevent the spread of COVID-19, and the perceived scarcity of ontological security played a mediating role in this process. Higher pandemic-induced disruption to patients' lives increased the ontological insecurity which further, in turn, reduced patients' good practice toward measures to prevent the novel coronavirus.

Conclusion: These findings provided direct evidence for the relationship between pandemic-induced disruption, scarcity of ontological security, and patients' prevention behavior. It suggested that there was a need to emphasize patients' ontological security. Overall, these findings suggested that it is important to emphasize the mental health among patients during the COVID-19 pandemic, and implement strategies to offer psychological support when needed.
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http://dx.doi.org/10.3389/fpubh.2022.865046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160831PMC
May 2022

Urinary tetracycline antibiotics exposure during pregnancy and maternal thyroid hormone parameters: A repeated measures study.

Sci Total Environ 2022 Sep 21;838(Pt 2):156146. Epub 2022 May 21.

School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Background: Studies on potential maternal thyrotoxicity related to tetracycline antibiotics exposure during pregnancy are lacking. Based on a large prospective cohort study, this study aimed to examine the associations between tetracycline antibiotics exposure in maternal urine and maternal thyroid hormone parameters.

Methods: Based on the Ma'anshan Birth Cohort study, urine and serum samples of 2969 pregnant women were collected in the first, second and third trimesters. Tetracycline antibiotics, including oxytetracycline, chlorotetracycline, tetracycline and doxycycline in urine samples, as well as free thyroxine (FT4), thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) levels in serum samples, were measured. Linear mixed models and multivariate linear regression models were employed to examine associations between tetracycline antibiotics exposure during pregnancy and maternal thyroid hormone parameters.

Results: The detection rates of four individual tetracycline antibiotics and all antibiotics (sum of four individual tetracycline antibiotics) in the three trimesters were 5.0%-52.3%, and the 95th percentile concentration ranged from 0.11 to 4.84 ng/mL. After adjusting for potential confounding factors, the repeated measures analyses indicated that pregnant women exposed to doxycycline and all antibiotics during the entire pregnancy were negatively associated with serum FT4 and TT4 levels but positively associated with serum TSH and TT3 levels. Trimester-stratified analyses found that doxycycline and all antibiotics exposure during the first trimester were negatively associated with serum FT4 and TT4 levels, while doxycycline was positively associated with TSH levels. In the third trimester, a significant association was only found between all antibiotics and TSH levels.

Conclusions: Our results suggest that exposure of pregnant women to tetracycline antibiotics is associated with maternal thyroid hormone parameters, and the first trimester might be the most critical window. More studies are needed to substantiate our findings and determine the underlying biological mechanisms.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156146DOI Listing
September 2022

A novel solar-powered electrochemical mineralization system for persistent remediation of uranium-contaminated groundwater.

J Environ Radioact 2022 Sep 18;250:106909. Epub 2022 May 18.

School of Resource & Environment and Safety Engineering, University of South China, Hengyang, 421001, China. Electronic address:

Reduction of the migratory ability of uranium via reduction, co-precipitation or immobilization is a widely used technology for remediation of uranium contaminated groundwater (UCG). However, the re-released uranium due to environmental alterations such as oxidation, acid dissolution, or microbial decomposition limits the long-term effect of UCG remediation. Here, we developed a novel solar-powered electrochemical mineralization (SPEM) system for persistent remediation of UCG under laboratory conditions. The SPEM system incorporates uranium into magnetite crystal to achieve long-term stability of uranium. The effects of photoelectric conversion, subsurface void fraction, groundwater seepage velocity, and electrode configuration on uranium removal were systematically analyzed. The results showed that the remediation system had excellent adaptability to complex water quality and geological conditions, and could remediate large-area contamination. After 12 h of persistent treatment, the system with newly hexagonal two-dimensional electrode configuration (1A6C) reduced uranium concentration by more than 85% in simulated subsurface environment. The mineralized uranium was not re-released within continuous rinsing of treated regions using an acid solution (pH = 3.0), for 370 h. The developed method solely requires metallic iron as a raw material, which has high and long-term efficiency, is eco-friendly, simple, and widely applicable, thus reliable for the remediation of deep UCG.
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http://dx.doi.org/10.1016/j.jenvrad.2022.106909DOI Listing
September 2022

CRISPR/Cas9-Mediated Knockout of the and Genes in BHK-21 Cell Promoted Seneca Virus A Replication and Enhanced Autophagy.

Front Cell Infect Microbiol 2022 27;12:865744. Epub 2022 Apr 27.

Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, China.

RNA interference (RNAi) is a major form of antiviral defense in host cells, and Ago2 and Dicer are the major proteins of RNAi. The Senecavirus A (SVA) is a reemerging virus, resulting in vesicular lesions in sows and a sharp decline in neonatal piglet production. In this study, CRISPR/Cas9 technology was used to knock out Ago2 and Dicer genes in BHK-21 cell lines used for SVA vaccine production. Cell clones with homozygous frameshift mutations of Ago2 and Dicer genes were successfully identified. The two knockout cell lines were named BHK-Dicer and BHK-Ago2. Results showed that the two genes' knockout cell lines were capable of stable passage and the cell growth rate did not change significantly. The replication rate and virus titers of SVA were significantly increased in knockout cell lines, indicating that RNAi could inhibit SVA replication. In addition, compared with normal cells, autophagy was significantly enhanced after SVA-infected knockout cell lines, while there was no significant difference in autophagy between the knockout and normal cell lines without SVA. The results confirmed that SVA could enhance the autophagy in knockout cells and promote viral replication. The two knockout cell lines can obtain viruses with high viral titers and have good application prospects in the production of SVA vaccine. At the same time, the RNAi knockout cell lines provide convenience for further studies on RNAi and SVA resistance to RNAi, and it lays a foundation for further study of SVA infection characteristics and screening of new therapeutic drugs and drug targets.
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http://dx.doi.org/10.3389/fcimb.2022.865744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093602PMC
April 2022

The correlation between ferroptosis and m6A methylation in patients with acute kidney injury.

Kidney Blood Press Res 2022 May 13. Epub 2022 May 13.

Objective: The present research analyzed the correlation between m6A methylation and ferroptosis associated genes (FAGs) in acute kidney injury (AKI) patients.

Methods: Bioinformatics analysis of microarray profiles (GSE30718) were performed to select differential expression genes (DEGs). FAGs are derived from systematic analysis of the aberrances and functional implications. The m6A methylation related genes were derived from the molecular characterization and clinical significance of m6A modulators. The multi-gene correlation of ferroptosis and M6A methylation modification were displayed. Then, the CIBERSORT algorithm was used to analyse the proportions of 22 immune cells infiltration.

Results: In total, 349 DEGs were extracted between the AKI and control samples, among which 172 genes were up-regulated and 177 were down-regulated. FAGs (SLC1A5, CARS, SAT1, ACSL4, NFE2L2, TFRC and MT1G) and m6A methylation related genes (YTHDF3, WTAP and IGF2BP3) were significantly increased in AKI patients (P< 0.05). FAGs (SAT1, ACSL4 and NFE2L2) was positively correlated with the expression level of m6A methylation genes (P< 0.05). NFE2L2 has high diagnostic value, and level of NFE2L2 was negatively correlated with the degree of follicular helper T (TFH) cells infiltration.

Conclusion: Our research could provide a new theoretical basis for the pathogenesis and immune mechanism of AKI.
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http://dx.doi.org/10.1159/000524900DOI Listing
May 2022

Hydrophobically Associating Polymers Dissolved in Seawater for Enhanced Oil Recovery of Bohai Offshore Oilfields.

Molecules 2022 Apr 24;27(9). Epub 2022 Apr 24.

Polymer Research Institute, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.

As compared to China's overall oil reserves, the reserve share of offshore oilfields is rather significant. However, offshore oilfield circumstances for enhanced oil recovery (EOR) include not just severe temperatures and salinity, but also restricted space on offshore platforms. This harsh oil production environment requires polymers with relatively strong salt resistance, solubility, thickening ability, rapid, superior injection capabilities, and anti-shearing ability. As a result, research into polymers with high viscosity and quick solubility is recognized as critical to meeting the criteria of polymer flooding in offshore oil reservoirs. For the above purposes, a novel hydrophobically associating polymer (HAP) was prepared to be used for polymer flooding of Bohai offshore oilfields. The synthetic procedure was free radical polymerization in aqueous solutions starting at 0 °C, using acrylamide (AM), acrylic acid (AA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and poly(ethylene glycol) octadecyl methacrylate (POM) as comonomers. It was discovered that under ideal conditions, the molecular weight of HAP exceeds 2.1 × 10 g⋅mol. In a simulated reservoir environment, HAP has substantially greater solubility, thickening property, and salt resistance than conventional polyacrylamide (HPAM), with equivalent molecular weight. Finally, the injectivity and propagation of the two polymers in porous media were investigated. Compared with HPAM, which has a similar molecular weight, HAP solution with the concentration of 0.175% had a much better oil displacement effect in the porous medium, which can enhance oil recovery by 8.8%. These discoveries have the potential to pave the way for chemical EOR in offshore oilfields.
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http://dx.doi.org/10.3390/molecules27092744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104856PMC
April 2022

Structural basis of peptidomimetic agonism revealed by small- molecule GLP-1R agonists Boc5 and WB4-24.

Proc Natl Acad Sci U S A 2022 05 13;119(20):e2200155119. Epub 2022 May 13.

Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective in treating type 2 diabetes and obesity with proven cardiovascular benefits. However, most of these agonists are peptides and require subcutaneous injection except for orally available semaglutide. Boc5 was identified as the first orthosteric nonpeptidic agonist of GLP-1R that mimics a broad spectrum of bioactivities of GLP-1 in vitro and in vivo. Here, we report the cryoelectron microscopy structures of Boc5 and its analog WB4-24 in complex with the human GLP-1R and Gs protein. Bound to the extracellular domain, extracellular loop 2, and transmembrane (TM) helices 1, 2, 3, and 7, one arm of both compounds was inserted deeply into the bottom of the orthosteric binding pocket that is usually accessible by peptidic agonists, thereby partially overlapping with the residues A8 to D15 in GLP-1. The other three arms, meanwhile, extended to the TM1-TM7, TM1-TM2, and TM2-TM3 clefts, showing an interaction feature substantially similar to the previously known small-molecule agonist LY3502970. Such a unique binding mode creates a distinct conformation that confers both peptidomimetic agonism and biased signaling induced by nonpeptidic modulators at GLP-1R. Further, the conformational difference between Boc5 and WB4-24, two closed related compounds, provides a structural framework for fine-tuning of pharmacological efficacy in the development of future small-molecule therapeutics targeting GLP-1R.
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http://dx.doi.org/10.1073/pnas.2200155119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171782PMC
May 2022

Association of Egg Consumption with Risk of All-Cause and Cardiovascular Disease Mortality: A Systematic Review and Dose-Response Meta-analysis of Observational Studies.

J Nutr 2022 May 7. Epub 2022 May 7.

Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Center.

Background: Recent studies have reported conflicting associations between egg consumption and the risk of all-cause or cardiovascular disease (CVD) mortality, including ischemic heart disease (IHD) mortality and stroke mortality. With accumulating evidence, up-to-date evidence about the association should be synthesized.

Objective: To assess the association of the risk of all-cause and CVD mortality with egg consumption.

Methods: We searched PubMed, EMBASE, and Web of Science databases through November 3, 2021 for observational studies conducted in participants ≥18 y of age and provided ORs or RRs or HRs and 95% CIs for ≥3 egg consumption categories or for increased intake of egg with the associations of interest. Random-effects model was used to pool the reported risk estimates. Restricted cubic splines were used to examine the dose-response association.

Results: Twenty-four articles with 48 reports (25 for all-cause mortality, 11 for CVD mortality, 6 for IHD mortality, and 6 for stroke mortality) involving 11,890,695 participants were included. Intake of each 1 egg/day increment was associated with increased risk of all-cause mortality (RR 1.06; 95% CI 1.02, 1.10; P = 0.008), but the association was restricted to women, Americans, and studies with adjustments for hyperlipidemia. Egg consumption was linearly associated with CVD mortality only in participants >60 y of age, Americans, studies with follow-up duration≥15 years, and adjustments for hyperlipidemia (P ≤0.018). No significant association was found between egg consumption and IHD or stroke mortality (P ≥0.080).

Conclusions: Egg consumption was linearly associated with a modestly risk of all-cause mortality and, in older participants, Americans, studies with longer follow-up or adjustments for hyperlipidemia, CVD mortality. These findings suggest that it may be prudent to avoid high egg consumption.
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http://dx.doi.org/10.1093/jn/nxac105DOI Listing
May 2022

Object-Specific Four-Path Network for Stroke Risk Stratification of Carotid Arteries in Ultrasound Images.

Comput Math Methods Med 2022 25;2022:2014349. Epub 2022 Apr 25.

Medical Ultrasound Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Atherosclerotic carotid plaques have been shown to be closely associated with the risk of stroke. Since patients with symptomatic carotid plaques have a greater risk for stroke, stroke risk stratification based on the classification of carotid plaques into symptomatic or asymptomatic types is crucial in diagnosis, treatment planning, and medical treatment monitoring. A deep learning technique would be a good choice for implementing classification. Usually, to acquire a high-accuracy classification, a specific network architecture needs to be designed for a given classification task. In this study, we propose an object-specific four-path network (OSFP-Net) for stroke risk assessment by integrating ultrasound carotid plaques in both transverse and longitudinal sections of the bilateral carotid arteries. Each path of the OSFP-Net comprises of a feature extraction subnetwork (FE) and a feature downsampling subnetwork (FD). The FEs in the four paths use the same network structure to automatically extract features from ultrasound images of carotid plaques. The FDs use different object-specific pooling strategies for feature downsampling based on the observation that the sizes and shapes in the feature maps obtained from FEs should be different. The object-specific pooling strategies enable the network to accept arbitrarily sized carotid plaques as input and to capture a more informative context for improving the classification accuracy. Extensive experimental studies on a clinical dataset consisting of 333 subjects with 1332 carotid plaques show the superiority of our OSFP-Net against several state-of-the-art deep learning-based methods. The experimental results demonstrate better clinical agreement between the ground truth and the prediction, which indicates its great potential for use as a risk stratification and as a monitoring tool in the management of patients at risk for stroke.
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http://dx.doi.org/10.1155/2022/2014349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061007PMC
May 2022

Subacute encephalitis in an immunocompetent patient diagnosed by next-generation sequencing.

J Int Med Res 2022 May;50(5):3000605221093217

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

is a free-living heterotrophic amoeba found in soil that causes a rare and usually fatal granulomatous amebic encephalitis. We report an immunocompetent patient infected with encephalitis diagnosed by next-generation sequencing (NGS). Clinical manifestations included sudden headache and epilepsy with disturbance of consciousness. The opening pressure of cerebrospinal fluid (CSF) was 220 mmHO, with mildly elevated white blood cell numbers and elevated protein levels. Cranial magnetic resonance imaging revealed abnormal signals in the right frontal lobe, left parietal lobe, and left occipital lobe. CSF NGS detected . Albendazole and metronidazole combined with fluconazole were administered to the patient immediately, but his condition deteriorated and he eventually died. Encephalitis caused by is rare and has a high mortality rate. Clinical manifestations are complex and diverse, but early diagnosis is very important for successful treatment. This can be aided by the metagenomic NGS of CSF.
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http://dx.doi.org/10.1177/03000605221093217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073125PMC
May 2022

Constructing new acid-activated anticancer peptide by attaching a desirable anionic binding partner peptide.

J Drug Target 2022 Jun 2:1-10. Epub 2022 Jun 2.

School of Pharmacy, Lanzhou University, Lanzhou, China.

Improving the cell selectivity of anticancer peptides (ACPs) is a major hurdle in their clinical utilisation. In this study, a new acid-activated ACP was designed by conjugating a cationic ACP LK to its anionic binding partner peptide (LEH) via a disulphide linker to trigger antitumor activity at acidic pH while masking its killing activity at normal pH. Three anionic binding peptides containing different numbers of glutamic acid (Glu) and histidine were engineered to obtain an efficient acid-activated ACP. The conjugates LK-LEH2 and LK-LEH3 exhibited 6.1- and 8.0-fold higher killing activity at pH 6.0 relative to at pH 7.4, respectively, suggesting their excellent pH-dependent antitumor activity; and their cytotoxicity was 10-fold lower than that of LK. However, LK-LEH4 had no pH-responsive killing effect. Interestingly, increasing the number of Glu from 2 to 4 increased the pH-response of the physical mixture of LK and LEH; conversely, they weakly decreased the cytotoxicity of LK, suggesting that the conjugate connection is required to achieve excellent pH dependence while maintaining minimum toxicity. LK-LEH2 and LK-LEH3 were more enzymatically stable than LK, indicating their potential for application. Our work provided a basis for designing promising ACPs with good selectivity and low toxicity.
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http://dx.doi.org/10.1080/1061186X.2022.2070627DOI Listing
June 2022
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