Publications by authors named "Di Zhao"

640 Publications

Multiphoton upconversion and non-resonant optical nonlinearity in perovskite quantum dot doped glasses.

Opt Lett 2021 Oct;46(20):5216-5219

By incorporating the quantum dots (QDs) into a glass host, we report for the first time, to our knowledge, the measurement of non-resonant optical nonlinearity and multiphoton upconversion (UC) processes for this QD-in-glass composite. We observe up to four-photon stable UC photoluminescence under excitation by infrared femtosecond pulses, low optical limiting thresholds, and high nonlinear optical absorption coefficients close to those of colloid processed metal halide perovskite (MHP) QDs. Combined with high robustness against air and moisture, the monolithic inorganic glass with incorporated MHP QDs could be a better platform for exploiting strong light-matter interaction for MHPs.
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http://dx.doi.org/10.1364/OL.438340DOI Listing
October 2021

An Overview of Eco-Driving Theory, Capability Evaluation, and Training Applications.

Sensors (Basel) 2021 Sep 30;21(19). Epub 2021 Sep 30.

State Key Laboratory of Automotive Simulation and Control, Jilin University, Changchun 130025, China.

Constrained by traditional fuel-saving technologies that have almost reached the limit of fuel-saving potential, the difficulty in changing urban congestion, and the low market penetration rate of new energy vehicles, in the short term, eco-driving seems to be an effective way to achieve energy-saving and emissions reduction in the transportation industry. This paper reviews the energy-saving theory and technology of eco-driving, eco-driving capability evaluation, and the practical application of eco-driving, and points out some limitations of previous studies. Specifically, the research on eco-driving theory mostly focuses on a single vehicle in a single scene, and there is a lack of eco-driving research for fleets or regions. In addition, the parameters used to evaluate eco-driving capabilities mainly focus on speed, acceleration, and fuel consumption, but external factors that are not related to the driver will affect these parameters, making the evaluation results unreasonable. Fortunately, vehicle big data and the Internet of Vehicles (V2I) provides an information basis for solving regional eco-driving, and it also provides a data basis for the study of data-driven methods for the fair evaluation of eco-driving. In general, the development of new technologies provides new ideas for solving some problems in the field of eco-driving.
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http://dx.doi.org/10.3390/s21196547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512309PMC
September 2021

The physical nature of the interaction in DMSO extraction separation of CH isomer/-decane systems.

Phys Chem Chem Phys 2021 Oct 13;23(39):22629-22639. Epub 2021 Oct 13.

School of Chemical & Environmental Engineering, China University of Mining & Technology (Beijing), Beijing 100083, China.

In this study, the liquid-liquid equilibrium of DMSO-CH aromatic isomer--decane systems was measured at 30 °C under atmospheric pressure at first, followed by Othmer-Tobias equation data reliability verification and NRTL/UNIQUAC activity coefficient model correlation. Moreover, intermolecular interaction energies and molecular polarity indexes (MPI) were calculated to interpret the extraction results. Finally, a set of wave function analyses was accomplished to elaborate the physical nature of the interaction in the DMSO extraction process. These investigations show that: (1) intermolecular interaction energy and the MPI results corroborate the aromatic and alkane extraction distribution coefficients well. (2) The interactions between aromatics and DMSO are weak hydrogen bonding and van der Waals (vdW) interactions. The attractive part mainly involves dispersion (49.57-53.30%) and electrostatic (35.49-37.83%) effects. (3) The interactions between aromatics and -decane are vdW interactions, dominated by attractive dispersion (70.41-70.93%) and repulsive exchange effects.
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http://dx.doi.org/10.1039/d1cp03128gDOI Listing
October 2021

A novel organic carbon accumulation mechanism in croplands in the Yellow River Delta, China.

Sci Total Environ 2021 Sep 28;806(Pt 2):150629. Epub 2021 Sep 28.

Environment Research Institute, Shandong University, Qingdao 266237, China. Electronic address:

The trends and mechanisms of organic carbon changes in coastal delta croplands are not yet clear due to the complexity physicochemical processes in soil. In this study, combing powder x-ray diffraction (XRD), microbial analysis, and density functional theory in quantum mechanics, we proposed a novel mechanism underlying OC accumulation. We investigated changes of three kinds of organic carbon (OC)-dissolved organic carbon (DOC), light fraction organic carbon (LFOC), and heavy fraction organic carbon (HFOC) in the Yellow River Delta croplands. We found that HFOC, dominant in coastal delta cropland soil, formed at different ages and its density increased with increasing reclamation time. Yet, DOC and LFOC had no significant increase or decrease tendency. Moreover, in coastal delta croplands, HFOC accumulation might be a complex progress, including the loss of indigenous OC and the accumulation of newly input OC. Based on these results, we proposed that although root exudative DOC (organic acids) could cause the indigenous OC loss by forming a specific microbial community, it still was a source of HFOC and promoted the OC accumulation. More importantly, based on density functional theory, we verified that these root exudative organic acids could adsorb on SiO together with crystalline Fe oxides (Fe) to form aggregates. The finding could explain the phenomenon that the XRD results showed samples were compounds of SiO, Fe, and OC and the accumulation of HFOC in coastal delta croplands. By revealing a new OC accumulation mechanism in coastal delta croplands, this study provides novel insights into the mechanism of OC dynamics in coastal delta croplands and the global carbon budget.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150629DOI Listing
September 2021

Changes of the Microbiota Composition on the Surface of Pig Carcasses during Chilling and Its Associations with Alterations in Chiller's Temperature and Air Humidity.

Foods 2021 Sep 16;10(9). Epub 2021 Sep 16.

Key Laboratory of Meat Processing and Quality Control, Ministry of Education, Key Laboratory of Meat Processing, Ministry of Agriculture and Rural Sciences, Jiangsu Collaborative Innovation Center for Quality Control of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

In this study, we investigated changes of microbiota composition on the surface of pig carcasses during chilling and their associations with temporal and spatial changes of wind speed, air temperature, and air humidity. The composition of microbiota on a carcass surface varied greatly with sampling sites; in particular, the surfaces of forelegs and neck had higher load of microorganisms and different microbiota composition compared to in the air and other carcass parts. However, such a difference in the microbiota composition decreased as chilling time extended. The positive detection ratios of microbial genes resistant to sulfonamides, quinolones, tetracyclines, and β-lactams were found different greatly with chilling time and sampling sites. The β-lactam and tetracycline resistant genes were observed in higher ratios in airborne microorganisms in the chiller, while the sulfa and tetracycline resistant genes had higher ratios in the microbiota on pig carcasses. Actual measurements and dynamic simulation showed that air temperature and humidity varied greatly among different places in a chiller within the first 8 h of chilling, with higher values close to the door, but the differences became smaller afterwards. The micro-environmental differences and changes in the chiller may cause the different composition of microbiota on pig carcasses.
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http://dx.doi.org/10.3390/foods10092195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471713PMC
September 2021

Xiaoyaosan Exerts Antidepressant Effect by Downregulating RAGE Expression in Cingulate Gyrus of Depressive-Like Mice.

Front Pharmacol 2021 7;12:703965. Epub 2021 Sep 7.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Xiaoyaosan (XYS), as a classic Chinese medicine compound, has been proven to have antidepressant effect in many studies, but its mechanism has not been clarified. In our previous studies, we found that chronic stress can induce depressive-like behavior and lead to emotion-related cingulate gyrus (Cg) dysfunction, as well as the decrease of neurotrophic factors and the increase of inflammatory-related proteins. Therefore, we speculated that XYS may play an antidepressant role by regulating the inflammation-related receptor of advanced glycation protein end product (RAGE) to affect the functional connectivity (FC) signal of the Cg and improve the depressive-like behavior. In order to verify this hypothesis, we analyzed the FC and RAGE expression in the Cg of depressive-like mice induced by chronic unpredictable mild stress (CUMS) and verified it with RAGE knockout mice. At the same time, we detected the effect of XYS on the depressive-like behavior, expression of RAGE, and the FC of the Cg of mice. The results showed that the FC of the Cg of depressive-like mice induced by CUMS was weakened, and the expression of RAGE was upregulated. The antidepressant effect of XYS is similar to that of fluoxetine hydrochloride, which can significantly reduce the depressive-like behavior of mice and inhibit the expression of the RAGE protein and mRNA in the Cg, and increase the FC of the Cg in mice. In conclusion, XYS may play an antidepressant role by downregulating the expression of RAGE in the Cg of depressive-like mice induced by CUMS, thereby affecting the functional signal and improving the depressive-like behavior.
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http://dx.doi.org/10.3389/fphar.2021.703965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452939PMC
September 2021

Identifying the different subtypes in menopausal symptoms among middle-aged women in China: a latent class analysis.

Menopause 2021 Sep 20. Epub 2021 Sep 20.

Department of Health Psychology, School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Objective: Many studies have focused on the severity and prevalence of menopausal symptoms among middle-aged women, which are limited by heterogeneity and diversity of subtypes. Subtyping facilitates the adaptation to prevention and clinical intervention strategies that target women. To determine the existence of significant subgroups of women with similar menopausal symptoms, a person-centered approach was used to identify potential profiles of women during the menopausal transition. In addition, we aimed to examine the association between latent subtypes and individual factors.

Methods: This cross-sectional study included 797 middle-aged women, aged 40 to 60 years, who were recruited from Shandong Province, China, between December 2017 and August 2018. We identified the subtypes in menopausal symptoms by performing a latent class analysis according to the self-reported Menopause Rating Scale and evaluated the robustness of our identified subtypes using a sensitivity analysis. Multinomial logistic regression was performed to explore the association between emergent latent subtypes and sociodemographic, clinical, and psychosocial characteristics.

Results: The mean age of participants was 49.83 ± 5.05 years. (1) Four potential classes were identified in middle-aged women: "severe symptoms" (14.9%), "dominant sleep-emotion symptoms" (31.4%), "physical/mental exhaustion symptoms" (32.5%), and "no symptoms" (21.2%). The four classes were also verified using a sensitivity analysis according to age and menopause status subgroups, which revealed the robust subtypes of menopausal symptoms. (2) The odds ratio of neuroticism, chronic diseases, and gynecological diseases were significantly higher for the "severe symptoms," "dominant sleep-emotion symptoms," and "physical/mental exhaustion symptoms" classes, compared to the "no symptoms" class, while the odds ratio of mindfulness and social support were lower.

Conclusions: A person-centered approach for middle-aged women could address the unmet need to understand the heterogeneity of menopausal symptoms. Subtyping facilitates the identification of the potential causes of menopausal symptoms and the development of personalized interventions.

Video Summary:http://links.lww.com/MENO/A830.
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http://dx.doi.org/10.1097/GME.0000000000001864DOI Listing
September 2021

Physical activity and the progression of coronary artery calcification.

Heart 2021 Nov 20;107(21):1710-1716. Epub 2021 Sep 20.

Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Background: The association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association between physical activity and CAC scores in apparently healthy adults.

Methods: Prospective cohort study of men and women free of overt cardiovascular disease who underwent comprehensive health screening examinations between 1 March 2011 and 31 December 2017. Baseline physical activity was measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) and categorised into three groups (inactive, moderately active and health-enhancing physically active (HEPA)). The primary outcome was the difference in the 5-year change in CAC scores by physical activity category at baseline.

Results: We analysed 25 485 participants with at least two CAC score measurements. The proportions of participants who were inactive, moderately active and HEPA were 46.8%, 38.0% and 15.2%, respectively. The estimated adjusted average baseline CAC scores (95% confidence intervals) in participants who were inactive, moderately active and HEPA were 9.45 (8.76, 10.14), 10.20 (9.40, 11.00) and 12.04 (10.81, 13.26). Compared with participants who were inactive, the estimated adjusted 5-year average increases in CAC in moderately active and HEPA participants were 3.20 (0.72, 5.69) and 8.16 (4.80, 11.53). Higher physical activity was association with faster progression of CAC scores both in participants with CAC=0 at baseline and in those with prevalent CAC.

Conclusion: We found a positive, graded association between physical activity and the prevalence and the progression of CAC, regardless of baseline CAC scores.
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http://dx.doi.org/10.1136/heartjnl-2021-319346DOI Listing
November 2021

Fecal Metabolomics and Network Pharmacology Reveal the Correlations between Constipation and Depression.

J Proteome Res 2021 Oct 15;20(10):4771-4786. Epub 2021 Sep 15.

Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China.

Constipation and depression are tightly related and often co-occur and coexist in clinic. Yet, the relationships and the underlying mechanisms are still unclear. Fecal metabolomics and network pharmacology were, for the first time, applied to investigate the potential correlations from multiple levels including classic behaviors, metabolomics, and gene targets. The behavioral indicators were analyzed, providing behavioral correlations at a macrolevel. Besides, fecal samples were analyzed by nuclear magnetic resonance spectroscopy to screen the shared and the unique metabolites and pathways, revealing correlations from a metabolic perspective. Finally, the disease targets and the functional pathways were obtained via network pharmacology, demonstrating correlations at the molecular level. The correlations between constipation and depression were demonstrated and supported by four-level evidence: (1) general behaviors, (2) gastrointestinal functions, (3) fecal metabolites and pathways, and (4) common gene targets and functional pathways. Especially, the correlations of behaviors and common metabolites showed that metabolites, including choline, betaine, and glycine, were significantly associated with constipation and depression. Besides, inflammation and immune abnormalities and energy metabolism were significantly involved in the mechanisms. The current findings prove the correlations between constipation and depression, and provide a basis for deeply understanding the comorbidities of constipation and depression.
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http://dx.doi.org/10.1021/acs.jproteome.1c00435DOI Listing
October 2021

The response of net primary productivity to climate change and its impact on hydrology in a water-limited agricultural basin.

Environ Sci Pollut Res Int 2021 Sep 13. Epub 2021 Sep 13.

Environment Research Institute, Shandong University, Qingdao, 266237, China.

Climate change has remarkably altered growing-season vegetation growth, but the impacts of vegetation variability on the regional hydrological cycle remain poorly understood. Exploring the relationships between climate change, vegetation dynamics, and hydrologic factors would contribute to the sustainable management of ecosystems. Here, we investigated the response of vegetation dynamics to climate change and its impact on hydrologic factors in a traditional agricultural basin with limited water resources in China, Nansi Lake Basin (NLB). To this end, CASA (Carnegie-Ames-Stanford Approach) model and the SWAT (Soil and Water Assessment Tool) model were applied to simulate the net primary productivity (NPP), evapotranspiration (ET), and soil water in the growing season (April-October) from 2000 to 2016. Results showed that the mean growing-season NPP (NPP) exhibited an ascending trend at a rate of 2.93 g C/m/year during the 17-year period. The intra-annual variation of NPP displayed two peaks in May and July, respectively. The first peak in May was accompanied by relative deficits in soil water, which might inhibit vegetation productivity. Precipitation was the principal climatic factor controlling NPP dynamics in the water-limited NLB. The positive influence of temperature on NPP was relatively weak, and even future warming could negatively affect ecosystem productivity in the south-central regions of the NLB. Furthermore, a strongly positive relationship between NPP and ET was detected, suggesting that increasing NPP in the future might stimulate the rise in ET and then exacerbate drought at the watershed scale. This study provides an integrated model for a comprehensive understanding of the interaction between vegetation, climate, and hydrological cycle, and highlights the importance of water-saving agriculture for future food security.
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http://dx.doi.org/10.1007/s11356-021-16458-xDOI Listing
September 2021

Glucosamine protects against neuronal but not vascular damage in experimental diabetic retinopathy.

Mol Metab 2021 Sep 20;54:101333. Epub 2021 Sep 20.

Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:

Objective: Glucosamine, an intermetabolite of the hexosamine biosynthesis pathway (HBP), is a widely used nutritional supplement in osteoarthritis patients, a subset of whom also suffer from diabetes. HBP is activated in diabetic retinopathy (DR). The aim of this study is to investigate the yet unclear effects of glucosamine on DR.

Methods: In this study, we tested the effect of glucosamine on vascular and neuronal pathology in a mouse model of streptozotocin-induced DR in vivo and on cultured endothelial and Müller cells to elucidate the underlying mechanisms of action in vitro.

Results: Glucosamine did not alter the blood glucose or HbA levels in the animals, but induced body weight gain in the non-diabetic animals. Interestingly, the impaired neuronal function in diabetic animals could be prevented by glucosamine treatment. Correspondingly, the activation of Müller cells was prevented in the retina as well as in cell culture. Conversely, glucosamine administration in the normal retina damaged the retinal vasculature by increasing pericyte loss and acellular capillary formation, likely by interfering with endothelial survival signals as seen in vitro in cultured endothelial cells. Nevertheless, under diabetic conditions, no further increase in the detrimental effects were observed.

Conclusions: In conclusion, the effects of glucosamine supplementation in the retina appear to be a double-edged sword: neuronal protection in the diabetic retina and vascular damage in the normal retina. Thus, glucosamine supplementation in osteoarthritis patients with or without diabetes should be taken with care.
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http://dx.doi.org/10.1016/j.molmet.2021.101333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479835PMC
September 2021

Investigation on the Mental Health Status of ICU Practitioners and Analysis of Influencing Factors During the Stable Stage of COVID-19 Epidemic in China.

Front Public Health 2021 18;9:572415. Epub 2021 Aug 18.

Department of Neurosurgery, The First Hospital of Hebei Medical University, Shijiazhuang, China.

To understand the impact of COVID-19 epidemic on the mental health status of intensive care unit (ICU) practitioners in China, and to explore the relevant factors that may affect the mental health status of front-line medical workers so as to adopt efficient and comprehensive measures in a timely manner to protect the mental health of medical staff. The study covered most of the provinces in China, and a questionnaire survey was conducted based on the WeChat platform and the Wenjuanxing online survey tool. With the method of anonymous investigation, we chose ICU practitioners to participate in the investigation from April 5, 2020 to April 7, 2020. The respondents were divided into two groups according to strict criteria of inclusion and exclusion, those who participated in the rescue work of COVID-19 (COVID-19 group) and those who did not (non-COVID-19 group). The SCL-90 self-evaluation scale was used for the evaluation of mental health status of the subjects. A total of 3,851 respondents completed the questionnaire. First, the overall mental health status of the targeted population, compared with the Chinese norm ( = 1,388), was reflected in nine related factor groups of the SCL-90 scale, and significant differences were found in every factor in both men and women, except for the interpersonal sensitivity in men. Second, the overall mental health of the non-COVID-19 group was worse than that of the COVID-19 group by the SCL-90 scale (OR = 1.98, 95% CI, 1.682-2.331). Third, we have revealed several influencing factors for their mental health in the COVID-19 group, current working status ( < 0.001), satisfaction of diet and accommodation ( < 0.05), occupational exposure ( = 0.005), views on the risk of infection ( = 0.034), and support of training ( = 0.01). The mental health status of the ICU practitioners in the COVID-19 group is better than that of the non-COVID-19 group, which could be attributed to a strengthened mentality and awareness of risks related to occupational exposure and enforced education on preventive measures for infectious diseases, before being on duty.
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http://dx.doi.org/10.3389/fpubh.2021.572415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416437PMC
September 2021

NOX5 mediates the crosstalk between tumor cells and cancer-associated fibroblasts via regulating cytokine network.

Clin Transl Med 2021 Aug;11(8):e472

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Activation of cancer-associated fibroblasts (CAFs) is a crucial feature for tumor malignancy. The reciprocal interplay between tumor cells and CAFs not only facilitates tumor progression and metastasis but also sustains the tumor-promoting function of CAFs. Nevertheless, how tumor cells readily adapt to these functional CAFs is still unclear. NADPH oxidase 5 (NOX5) is a strong reactive oxygen species producer overexpressed in esophageal squamous cell carcinoma (ESCC) cells. In this study, we showed that NOX5-positive ESCC cells induced normal fibroblasts (NFs) or adipose-derived mesenchymal stem cells (MSCs) to express the marker of CAFs-α smooth muscle actin. Moreover, these tumor cells reprogrammed the cytokine profile of the activated CAFs, which further stimulated NFs or MSCs to CAFs and induced lymphangiogenesis to facilitate ESCC malignancy. NOX5 activated intratumoral Src/nuclear factor-κB signaling to stimulate secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and lactate from tumor cells. Subsequently, TNF-α, IL-1β, and lactate activated CAFs, and facilitated the secretion of IL-6, IL-7, IL-8, CCL5, and transforming growth factor-β1 from CAFs. These CAFs-derived cytokines reciprocally induced the progression of NOX5-positive ESCC cells. Our findings together indicate that NOX5 serves as the driving oncoprotein to provide a niche that is beneficial for tumor malignant progression.
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http://dx.doi.org/10.1002/ctm2.472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329696PMC
August 2021

Cardiovascular and Obstetric Delivery Complications in Pregnant Women With Valvular Heart Disease.

Am J Cardiol 2021 11 24;158:90-97. Epub 2021 Aug 24.

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs <0.1%). At delivery, they had higher adjusted odds of obstetric events including preeclampsia and/or eclampsia (aOR 1.9 [1.8 to 2.2]) and intrapartum/postpartum hemorrhage (aOR 1.4 [1.2 to 1.6]), and cardiovascular events including peripartum cardiomyopathy (aOR 65 [53 to 78]), pulmonary edema (aOR 17 [13 to 22]), acute ischemic heart disease (aOR 19 [12 to 30]) and arrhythmias (aOR 22 [19 to 27]). There were valve lesion-specific differences in the magnitude of risk but both stenotic and regurgitant lesions were associated with elevated risk of cardiovascular complications. In conclusion, pregnant women with stenotic and regurgitant valvular disease have a greater burden of cardiovascular comorbidities and increased odds of obstetric and cardiovascular events at delivery. These women may benefit from specialized care from a Cardio-Obstetrics team.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.038DOI Listing
November 2021

Effect of Pterostilbene, a Natural Derivative of Resveratrol, in the Treatment of Colorectal Cancer through Top1/Tdp1-Mediated DNA Repair Pathway.

Cancers (Basel) 2021 Aug 9;13(16). Epub 2021 Aug 9.

Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Topoisomerase 1 (Top1) inhibitor is an effective anticancer drug, but several factors limit its clinical application such as drug inactivation, tyrosyl-DNA phosphodiesterase 1 (Tdp1)-mediated tumor drug resistance, and its toxicity. Our previous study identified pterostilbene (PTE) and resveratrol (RE) to suppress these two proteins by binding to their active center. PTE and RE could inhibit the proliferation of various colorectal cancer cells, induce cell apoptosis, and make cell cycle stay in G2/M phase in vitro. PTE and RE could decrease Top1 and Tdp1 contents and mRNA expression in wild-type, constructed 1 overexpressing CL187, 1- or 1- silenced CL187 cell lines. PTE exhibited excellent antitumor activity in subcutaneous CL187 transplantation model (TGI = 79.14 ± 2.85%, 200 mg/kg, i.p.) and orthotopic transplantation model (TGI = 76.57 ± 6.34%, 100 mg/kg, i.p.; TGI = 72.79 ± 4.06%, 500 mg/kg, i.g.) without significant toxicity. PTE had no significant inhibitory effect on non-tumor cell proliferation in vitro and would not induce damage to liver, kidney, and other major organs. Overall, PTE and RE can inhibit the activity of Top1 enzyme and inhibit the DNA damage repair pathway mediated by Top1/Tdp1, and can effectively inhibit colorectal cancer development with low toxicity, thus they have great potential to be developed into a new generation of anti-tumor drugs.
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http://dx.doi.org/10.3390/cancers13164002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391236PMC
August 2021

Anion-exchange-mediated internal electric field for boosting photogenerated carrier separation and utilization.

Nat Commun 2021 Aug 16;12(1):4952. Epub 2021 Aug 16.

Department of Chemistry, Tsinghua University, Beijing, China.

Heterojunctions modulated internal electric field (IEF) usually result in suboptimal efficiencies in carrier separation and utilization because of the narrow IEF distribution and long migration paths of photocarriers. In this work, we report distinctive bismuth oxyhydroxide compound nanorods (denoted as BOH NRs) featuring surface-exposed open channels and a simple chemical composition; by simply modifying the bulk anion layers to overcome the limitations of heterojunctions, the bulk IEF could be readily modulated. Benefiting from the unique crystal structure and the localization of valence electrons, the bulk IEF intensity increases with the atomic number of introduced halide anions. Therefore, A low exchange ratio (~10%) with halide anions (I, Br, Cl) gives rise to a prominent elevation in carrier separation efficiency and better photocatalytic performance for benzylamine coupling oxidation. Here, our work offers new insights into the design and optimization of semiconductor photocatalysts.
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http://dx.doi.org/10.1038/s41467-021-25261-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368037PMC
August 2021

Treatment of postoperative delirium with continuous theta burst stimulation: study protocol for a randomised controlled trial.

BMJ Open 2021 08 16;11(8):e048093. Epub 2021 Aug 16.

Department of Psychiatry, Shanghai Tenth People's Hospital, Shanghai, China

Introduction: Postoperative delirium is one of the most common postoperative complications among elderly patients (65 years old or older). However, there are no effective treatments for this condition. Recent research suggests that continuous theta burst stimulation (cTBS), a non-invasive brain stimulation, can reduce pain level, improve cognitive function and affective symptoms in multiple diseases or dysfunctions, including anxiety disorders, major depressive disorder, sleep disorders and pain. But the potential benefits of cTBS in reducing postoperative delirium have not been investigated. Therefore, we propose determining whether cTBS can prevent and/or treat postoperative delirium in senior patients.

Methods And Analysis: The study will be a double-blind, randomised controlled trial. Participants (65 years old or older) undergoing scheduled orthopaedic surgery (≥2 hours, general anaesthesia) will be randomised to receive either cTBS or sham stimulation with a focal figure-of-eight coil over the right dorsolateral prefrontal cortex at 80% of the resting motor threshold. Every patient will receive 2-3 sets of stimulations during postoperative days (40 s per session, 3 sessions per set, 1 set per day). Participants will be assessed twice daily by a research assistant blinded to allocation. The primary outcome will be the incidence of postoperative delirium measured by the Confusion Assessment Method on postoperative days 1, 2 and 3. The secondary outcomes will be the severity and duration of postoperative delirium, cognitive function, pain, sleep quality, activities of daily living, length of hospital stay, discharge-to-facility or home, and rate of complication and mortality during the hospital stay.

Ethics And Dissemination: Ethical approval has been obtained from the ethics committee of Shanghai 10th People's Hospital. The principal investigator will submit a research progress report to the ethics committee regularly. All participants will provide written informed consent. Study results will be published in a peer-reviewed journal.

Trial Registration Number: NCT04661904.
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http://dx.doi.org/10.1136/bmjopen-2020-048093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370542PMC
August 2021

Large-scale transcriptome sequencing in broiler chickens to identify candidate genes for breast muscle weight and intramuscular fat content.

Genet Sel Evol 2021 Aug 16;53(1):66. Epub 2021 Aug 16.

Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding; Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes; School of Life Science and Engineering, Foshan University, #33 Guang-yun-lu, Shishan, Nanhai, Foshan, 528231, Guangdong, People's Republic of China.

Background: In broiler production, breast muscle weight and intramuscular fat (IMF) content are important economic traits. Understanding the genetic mechanisms that underlie these traits is essential to implement effective genetic improvement programs. To date, genome-wide association studies (GWAS) and gene expression analyses have been performed to identify candidate genes for these traits. However, GWAS mainly detect associations at the DNA level, while differential expression analyses usually have low power because they are typically based on small sample sizes. To detect candidate genes for breast muscle weight and IMF contents (intramuscular fat percentage and relative content of triglycerides, cholesterol, and phospholipids), we performed association analyses based on breast muscle transcriptomic data on approximately 400 Tiannong partridge chickens at slaughter age.

Results: First, by performing an extensive simulation study, we evaluated the statistical properties of association analyses of gene expression levels and traits based on the linear mixed model (LMM) and three regularized linear regression models, i.e., least absolute shrinkage and selection operator (LASSO), ridge regression (RR), and elastic net (EN). The results show that LMM, LASSO and EN with tuning parameters that are determined based on the one standard error rule exhibited the lowest type I error rates. Using results from all three models, we detected 43 candidate genes with expression levels that were associated with breast muscle weight. In addition, candidate genes were detected for intramuscular fat percentage (1), triglyceride content (2), cholesterol content (1), and phospholipid content (1). Many of the identified genes have been demonstrated to play roles in the development and metabolism of skeletal muscle or adipocyte. Moreover, weighted gene co-expression network analyses revealed that many candidate genes were harbored by gene co-expression modules, which were also significantly correlated with the traits of interest. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these modules are involved in muscle development and contraction, and in lipid metabolism.

Conclusions: Our study provides valuable insight into the transcriptomic bases of breast muscle weight and IMF contents in Chinese indigenous yellow broilers. Our findings could be useful for the genetic improvement of these traits in broiler chickens.
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http://dx.doi.org/10.1186/s12711-021-00656-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369645PMC
August 2021

Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study.

Front Med (Lausanne) 2021 30;8:710452. Epub 2021 Jul 30.

Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China.

This study aimed to investigate the long-term efficacy of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). In this single-center long-term follow-up study, FMT treatment was administered to patients with moderate to severe IBS (IBS severity scoring system (IBS-SSS) > 175). After 1 year of treatment, it was decided whether to repeat FMT based on IBS-SSS score (IBS-SSS > 175). Baseline characteristics before and after FMT and questionnaires were completed at 1, 3, 6, 12, 24, 36, 48, and 60 months after FMT. The study outcomes included treatment efficacy rates, change of IBS-SSS, IBS-specific quality of life and fatigue, effect on stool frequency, Bristol Stool Scale for IBS-C and IBS-D, and side effects. A total of 227 patients (47.58% IBS-C, 39.21% IBS-D, and 13.22% IBS-M) were recruited (142 females and 85 males with a mean age of 41.89 ± 13.57 years). The efficacy rates were 108 (51.92%), 147 (74.62%), 125 (74.41 %), 88 (71.54%), 78 (75.00%), 65 (73.03%), 45 (61.64%), and 37 (62.71%) at different follow-up time points. The total IBS-SSS score was 321.37 ± 73.89 before FMT, which significantly decreased after 1 month. The IBS-specific quality of life (IBS-QoL) score was 40.24 ± 11.34 before FMT, increased gradually, and was significantly higher at 3 months compared to before FMT. The total Fatigue Assessment Scale (FAS) score was 47 ± 8.64 before FMT and was significantly lower at 3 months. During follow-up, 89 (39.21%) side effects occurred that were alleviated by symptomatic treatment, and no serious adverse events were detected. Based on 60 months of long-term follow-up, the safety and efficacy of FMT for IBS was established. However, as the treatment effect declines over time, periodic and repetitive FMT is required for a sustained effect.
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http://dx.doi.org/10.3389/fmed.2021.710452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362996PMC
July 2021

Neurophysiological correlate of incubation of craving in individuals with methamphetamine use disorder.

Mol Psychiatry 2021 Aug 12. Epub 2021 Aug 12.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Previous studies both in laboratory animals and humans have reported that abstinence induces incubation of cue-induced drug craving for nicotine, alcohol, cocaine, and methamphetamine. However, current experimental procedures utilized to study incubation of methamphetamine craving do not incorporate the temporal dynamics of neuropsychological measures and electrophysiological activities associated with this incubation process. This study utilized the high-density electroencephalogram (EEG) signals as a rapid, inexpensive, and noninvasive measure of cue-induced craving potential. A total of 156 male individuals with methamphetamine use disorder (MUD) enrolled in this multisite, cross-sectional study. Structured clinical interview data, self-report questionnaires (cued craving, quality of sleep, impulsivity, anxiety, and depression) and resting-state, eye-closed 128 high-density channel EEG signals were collected at 5 abstinence duration time points (<1, 1-3, 3-6, 6-12, and 12-24 months) to track the neuropsychological and neurophysiological signatures. Cue-induced craving was higher after 1-3 months than after the other time points. This incubation effect was also observed for sleep quality but not for anxiety, depression, and impulsivity symptoms, along with exhibited decreased power spectrum for theta (5.5-8 Hz) and alpha (8-13 Hz), and increased in beta (16.5-26.5 Hz) frequency band. Source reconstructed resting-state EEG analysis showed increased synchronization of medial prefrontal cortex (MPFC) for the beta frequency band in 1-3 months abstinent MUD group, and associated with the incubation of craving. Remarkably, the robust incubation-related abnormalities may be driven by beta-band source space connectivity between MPFC and bilateral orbital gyrus (ORB). Our findings suggest the enhancement of beta activity in the incubation period most likely originates from a dysfunction involving frontal brain regions. This neurophysiological signature of incubation of craving can be used to identify individuals who might be most susceptible to relapse, providing a potential insight into future therapeutic interventions for MUD via neuromodulation of beta activity.
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http://dx.doi.org/10.1038/s41380-021-01252-5DOI Listing
August 2021

Correction to: Enhanced adsorption of phosphorus in soil by lanthanum-modified biochar: improving phosphorus retention and storage capacity.

Environ Sci Pollut Res Int 2021 Aug 12. Epub 2021 Aug 12.

Ministry of Agriculture and Rural Affairs, Agro-Environmental Protection Institute, Tianjin, 300191, China.

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http://dx.doi.org/10.1007/s11356-021-15892-1DOI Listing
August 2021

Efficient Adsorption of Deoxynivalenol by Porous Carbon Prepared from Soybean Dreg.

Toxins (Basel) 2021 07 18;13(7). Epub 2021 Jul 18.

National Soybean Processing Industry Technology Innovation Center, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China.

A novel porous carbon adsorbent for the removal of deoxynivalenol was prepared from soybean dreg (SD). The new material was characterized by scanning electron microscopy equipped with energy dispersive X-ray spectroscopy (SEM-EDS), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) analysis, N adsorption/desorption measurement techniques, X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The specific surface area of the SDB-6-KOH was found to be 3655.95 m g, the pore volume was 1.936 cm g and the average pore size was 2.125 nm. The high specific surface area and effective functional groups of the carbon material promoted the adsorption of deoxynivalenol. By comparing the adsorption effect of SDB-6-X prepared with different activators (X: KOH, KCO, KHCO), SDB-6-KOH had the highest adsorption capacity. The maximum adsorption capacity of SDB-6-KOH to deoxynivalenol was 52.9877 µg mg, and the removal efficiency reached 88.31% at 318 K. The adsorption kinetic and isotherm data were suitable for pseudo-second-order and Langmuir equations, and the results of this study show that the novel carbon material has excellent adsorptive ability and, thus, offers effective practical application potential for the removal of deoxynivalenol.
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http://dx.doi.org/10.3390/toxins13070500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310275PMC
July 2021

A deep-learning-based framework for severity assessment of COVID-19 with CT images.

Expert Syst Appl 2021 Dec 27;185:115616. Epub 2021 Jul 27.

MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Millions of positive COVID-19 patients are suffering from the pandemic around the world, a critical step in the management and treatment is severity assessment, which is quite challenging with the limited medical resources. Currently, several artificial intelligence systems have been developed for the severity assessment. However, imprecise severity assessment and insufficient data are still obstacles. To address these issues, we proposed a novel deep-learning-based framework for the fine-grained severity assessment using 3D CT scans, by jointly performing lung segmentation and lesion segmentation. The main innovations in the proposed framework include: 1) decomposing 3D CT scan into multi-view slices for reducing the complexity of 3D model, 2) integrating prior knowledge (dual-Siamese channels and clinical metadata) into our model for improving the model performance. We evaluated the proposed method on 1301 CT scans of 449 COVID-19 cases collected by us, our method achieved an accuracy of 86.7% for four-way classification, with the sensitivities of 92%, 78%, 95%, 89% for four stages. Moreover, ablation study demonstrated the effectiveness of the major components in our model. This indicates that our method may contribute a potential solution to severity assessment of COVID-19 patients using CT images and clinical metadata.
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http://dx.doi.org/10.1016/j.eswa.2021.115616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314790PMC
December 2021

[Determination of vitamin A, vitamin E isomers and cholesterol in foods by reversed-phase high-performance liquid chromatography].

Wei Sheng Yan Jiu 2021 Jul;50(4):615-619

Center for Disease Control and Prevention of Shaanxi Province, Xi'an 710054, China.

Objective: To establish a method for simultaneous analysis of vitamin A, three vitamin E isomers and cholesterol in meat products by reversed-phase high-performance liquid chromatography. This method is used to determine the contents of the corresponding nutrients in several meat products.

Methods: The sample was pretreated with saponification and liquid-liquid extraction, then separated on Waters Symmetry C_(18) column(4.6 mm×250 mm, 5 μm). The mobile phase consisted of methanol(98%) and water(2%). The analytes were detected by photo-diode array(PDA)detector. 325 nm, 294 nm, and 210 nm were selected as the characteristic absorption wavelengths of vitamin A, vitamin E, and cholesterol, respectively by scanning in the range of 190-350 nm in 3 D mode. Benzo[e]pyrene was internal standard for vitamin A and E. Cholesterol was quantified by external standard curve method.

Results: The concentration of vitamin A, three vitamin E isomers and cholesterol showed good linearity in the range of 0.18-9.00 μg/mL、0.76-5.2 μg/mL and 0.11-5.50 mg/mL, respectively, with the correlation coefficients greater than 0.995.The limits of detections(LODs) were 5、20 and 330 μg/100 g and the limits of quantification(LOQs) for vitamin A, three vitamin E isomers and cholesterol were 15、60 and 990 μg/100 g, respectively. The recoveries at three levels in the matrix were 86.3%-105.6%, and the relative standard deviations(RSDs) were all less than 7.0%(n=6).

Conclusion: The method is sensitive, accurate and suitable for analysis of vitamin A, three vitamin E isomers and cholesterol in meat products.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.04.013DOI Listing
July 2021

Development of a Mobile App for Ecological Momentary Assessment of Circadian Data: Design Considerations and Usability Testing.

JMIR Form Res 2021 Jul 23;5(7):e26297. Epub 2021 Jul 23.

Division of Health Sciences Informatics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Background: Collecting data on daily habits across a population of individuals is challenging. Mobile-based circadian ecological momentary assessment (cEMA) is a powerful frame for observing the impact of daily living on long-term health.

Objective: In this paper, we (1) describe the design, testing, and rationale for specifications of a mobile-based cEMA app to collect timing of eating and sleeping data and (2) compare cEMA and survey data collected as part of a 6-month observational cohort study. The ultimate goal of this paper is to summarize our experience and lessons learned with the Daily24 mobile app and to highlight the pros and cons of this data collection modality.

Methods: Design specifications for the Daily24 app were drafted by the study team based on the research questions and target audience for the cohort study. The associated backend was optimized to provide real-time data to the study team for participant monitoring and engagement. An external 8-member advisory board was consulted throughout the development process, and additional test users recruited as part of a qualitative study provided feedback through in-depth interviews.

Results: After ≥4 days of at-home use, 37 qualitative study participants provided feedback on the app. The app generally received positive feedback from test users for being fast and easy to use. Test users identified several bugs and areas where modifications were necessary to in-app text and instructions and also provided feedback on the engagement strategy. Data collected through the mobile app captured more variability in eating windows than data collected through a one-time survey, though at a significant cost.

Conclusions: Researchers should consider the potential uses of a mobile app beyond the initial data collection when deciding whether the time and monetary expenditure are advisable for their situation and goals.
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http://dx.doi.org/10.2196/26297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367152PMC
July 2021

Problem-solving deficits in methcathinone use disorder.

Psychopharmacology (Berl) 2021 Sep 22;238(9):2515-2524. Epub 2021 Jul 22.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping South Road 600, Xuhui, Shanghai, China.

Rationale: The use of methcathinone (MCAT), a psychostimulant drug that can lead to long-term health risks and executive dysfunction, increased to an alarming rate in recent years. Impairments in low-level executive function have been reported in substance use disorder. However, little empirical evidence is available regarding high-level executive function (e.g., problem solving), which may act as a risk factor for relapse.

Objectives: The present study aimed to investigate whether the problem-solving ability was altered in abstinent individuals with methcathinone use disorder (MCUD). Here, we tested fifty male MCUD individuals (short-term MCUD group: twenty-nine patients with MCAT use less than 3 years, long-term MCUD group: twenty-one patients with MCAT use longer than 3 years, which were split by medium years of drug use) and twenty-four well-matched healthy controls (HC) in the Tower of Hanoi task (TOH) to assess the impact of task difficulty on drug-related changes in problem-solving performance. We used several measures to characterize problem-solving performance: the number of mistakes made, the completion time of the task, and the thinking time before the first move.

Results: In the low task difficulty condition, the MCUD group and HC group showed similar levels of mistakes and completion time, while in the high task difficulty condition, the MCUD group reported more mistakes (the mean number of mistakes in each trial: 1.41 ± 1.15 vs 0.79 ± 0.76, P = 0.019, Cohen's d = 0.635) and longer completion time in the task (the mean completion time in each trial: 45.83 ± 20.51 s vs 33.40 ± 15.10 s, P = 0.010, Cohen's d = 0.690) than the HC group. The thinking time before the first move did not differ significantly between groups (P = 0.257). We further found that the long-term (more than 3 years) MCUD group made more mistakes than the short-term MCUD group and HC group, mainly in the highly difficult subtasks. The longer time than HCs was reported in the long-term MCUD group among high task difficulty of subtasks. In addition, there was a positive correlation between years of MCAT use and the number of mistakes made in high task difficulty TOH task (r = 0.326, P = 0.021).

Conclusions: Chronic methcathinone use was associated with deficits in problem-solving performance, which depended on the degree of task difficulty. The impairment was more evident in the long-term (> 3 years) MCAT group.
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http://dx.doi.org/10.1007/s00213-021-05874-zDOI Listing
September 2021

Enhanced adsorption of phosphorus in soil by lanthanum-modified biochar: improving phosphorus retention and storage capacity.

Environ Sci Pollut Res Int 2021 Jul 20. Epub 2021 Jul 20.

Ministry of Agriculture and Rural Affairs, Agro-Environmental Protection Institute, Tianjin, 300191, China.

Use of soil adsorbent is an effective method for the promotion of phosphorus adsorption capacity of soil, though most of the soil adsorbents have weak phosphorus retention ability. Herein, we compared the traditional gypsum (GP) and zeolite (ZP) adsorbents to explore the phosphorus retention ability of lanthanum modified walnut shell biochar (La-BC) in soil. The results showed that with the increase of exogenous phosphorus concentration, the adsorption amount of phosphorus by adsorbents in soil increased at first and then tended to be stable. The maximum adsorption capacity of soil to phosphorus is gypsum, lanthanum-modified biochar > zeolite, and the addition of lanthanum-modified biochar can improve the adsorption capacity of soil to phosphorus, enhance the binding strength of soil and phosphorus, improve the ability of soil to store phosphorus, reducing phosphorus adsorption saturation, and is beneficial to control the leaching of soil phosphorus. FTIR and XRD analysis showed that the adsorption of phosphorus by each adsorbent in soil was mainly chemical precipitation. The response surface analysis showed that the adsorption performance of La-BC+S was the best when the concentration of exogenous phosphorus was 50.0 mg/L, pH was 6.47, and the reaction time was 436.98 min. This study provides a reference for soil adsorbents to hold phosphorus and reduce the risk of phosphorus leaching to avoid groundwater pollution.
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http://dx.doi.org/10.1007/s11356-021-15364-6DOI Listing
July 2021

Protective Effect of Zinc Oxide and Its Association with Neutrophil Degranulation in Piglets Infected with Porcine Epidemic Diarrhea Virus.

Oxid Med Cell Longev 2021 23;2021:3055810. Epub 2021 Jun 23.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.

Porcine epidemic diarrhea virus (PEDV) has reemerged throughout the world in the past ten years and caused huge economic losses to the swine industry. No drugs are available to prevent or treat PEDV infection in piglets. Zinc oxide (ZnO) has been shown to reduce diarrhea. However, little is known about its role in PEDV infection. In this study, twenty-four 7-day-old piglets were randomly divided into three treatment groups: control, PEDV, and ZnO+PEDV. Piglets in the ZnO+PEDV group were orally administered with 100 mg/kg·BW ZnO and then inoculated PEDV at a dose of 10 TCID (50% tissue culture infectious dose) per pig. Growth performance, histologic lesions, viral load, indicators of intestinal damage, inflammation, and oxidative stress were recorded or detected to determine the effect of ZnO on PEDV infection. And the underlying mechanisms were revealed by microarray and proteomic analyses. Results showed that ZnO administration mitigated diarrhea and the reduction of average daily weight gain induced by PEDV infection. ZnO could inhibit PEDV replication in the small intestine and colon. Both villus height and crypt depth were affected by PEDV infection in the duodenum and jejunum, which could be rescued by ZnO administration. Moreover, the activity of catalase was decreased both in plasma and intestine after PEDV infection, while increased in the intestine by ZnO administration. PEDV infection also significantly increased the concentration of HO in jejunal and ileum and decreased the activity of total superoxide dismutase and glutathione peroxidase in plasma, whereas ZnO administration obviously increased the activity of total superoxide dismutase and decreased the concentration of HO in the ileum. The concentrations of IL-1, IL-6, and IL-8 in the plasma were all decreased upon ZnO administration. A large number of differentially expressed genes and proteins were identified in the ileum among the three groups by microarray and proteomic analyses. Gene Ontology and Reactome pathway analyses indicated that neutrophil degranulation and nutrient metabolism were the main biological process and pathways in both PEDV infection and ZnO administration. Overall, ZnO administration could improve growth performance, intestinal redox status, morphology, and function and reduce diarrhea in PEDV-infected piglets; ZnO could exert antiviral and anti-inflammatory effects on PEDV-infected piglets probably through regulating neutrophil degranulation. Our findings have important implications in piglet and infant nutrition.
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http://dx.doi.org/10.1155/2021/3055810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249118PMC
June 2021

Pharmacokinetics and Safety of a Single Dose and Multiple Doses of Allisartan Isoproxil, an Angiotensin II Receptor Blocker, in Healthy Chinese People.

Clin Pharmacol Drug Dev 2021 Jul 8. Epub 2021 Jul 8.

Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Allisartan isoproxil (AI) is a blocker of the angiotensin II type 1 receptor. We evaluated the safety and pharmacokinetics of single- and multiple-dose AI in healthy Chinese individuals. Participants were assigned to receive AI or placebo. Plasma concentration of EXP3174 (carboxylic acid derivative) was measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental methods. Twelve subjects were enrolled, and the ratio of men to women was 5:1. Main pharmacokinetic parameters of EXP3174 after single and multiple doses of AI were a mean maximum concentration in plasma (C ) of 2242 ± 1037 ng/mL and median time to reach C (T ) of 3.5 hours (2.5-8 hours). The median T at steady state was 4.0 hours (1.5-8 hours). The mean C at steady state (C ) was 2047 ± 1050 ng/mL. In terms of EXP3174, there was no significant difference in the C , area under the curve from time zero to 24 hours of quantifiable concentration at steady state (AUC ), and AUC after multiple doses of AI. Serious adverse events did not occur. These data suggest that AI is safe and well tolerated in healthy Chinese individuals at a single dose of 480 or 480 mg once daily for 7 days.
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http://dx.doi.org/10.1002/cpdd.995DOI Listing
July 2021

PTPRM methylation induced by FN1 promotes the development of glioblastoma by activating STAT3 signalling.

Pharm Biol 2021 Dec;59(1):904-911

Department of Neurosurgery, The Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.

Context: The phosphorylation of signal transducer and activator of transcription protein 3 (STAT3) is up-regulated in glioblastoma (GBM) cells and is regulated by protein tyrosine phosphatase receptor type M (PTPRM). Fibronectin-1 (FN1) is also reported to be up-regulated in GBM.

Objective: We explored the role of FN1-induced PTPRM methylation in GBM.

Materials And Methods: The lentivirus particles of oe-PTPRM, sh-PTPRM, oe-FN1, sh-FN1, or their negative controls (NSCs) were transfected into GBM cells with or without stattic (0.5 μM, 24 h) or 5-aza (1 μM, 0, 2, 4 h) treatments. Methylation-specific PCR was performed to detect PTPRM methylation levels.

Results: PTPRM was down-regulated (0.373 ± 0.124- and 0.455 ± 0.109-fold), FN1 and p-STAT3 were up-regulated ( < 0.001) in A172 and U87 MG cells as compared to NSCs. Overexpressing PTPRM inhibited STAT3 phosphorylation. Interfering with PTPRM increased colony numbers in A172 and U-87 MG cells (2.253 ± 0.111- and 2.043 ± 0.19-fold), and stattic reduced them. Cell viability was reduced after treatment with 5-aza in A172 and U-87 MG cells ( < 0.05). P-STAT3 was down-regulated after 5-aza treatment. Overexpressing FN1 decreased PTPRM levels ( < 0.001), knockdown of FN1 decreased PTPRM methylation and inhibited STAT3 phosphorylation. Overexpressing FN1 increased cell viability (1.497 ± 0.114- and 1.460 ± 0.151-fold), and stattic or 5-aza reversed such effects ( < 0.05).

Discussion And Conclusions: The up-regulation of FN1 reduced PTPRM by increasing its methylation, resulting in an increase of STAT3 phosphorylation and promoting GBM cell proliferation. Interfering with FN1 may be a potential therapeutic target for GBM.
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http://dx.doi.org/10.1080/13880209.2021.1944220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259858PMC
December 2021
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