Publications by authors named "Ping Yang"

1,922 Publications

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Pairwise Difference Regression: A Machine Learning Meta-algorithm for Improved Prediction and Uncertainty Quantification in Chemical Search.

J Chem Inf Model 2021 Aug 4. Epub 2021 Aug 4.

Computer, Computational, and Statistical Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States.

Machine learning (ML) plays a growing role in the design and discovery of chemicals, aiming to reduce the need to perform expensive experiments and simulations. ML for such applications is promising but difficult, as models must generalize to vast chemical spaces from small training sets and must have reliable uncertainty quantification metrics to identify and prioritize unexplored regions. computational chemistry and chemical intuition alike often take advantage of differences between chemical conditions, rather than their absolute structure or state, to generate more reliable results. We have developed an analogous comparison-based approach for ML regression, called pairwise difference regression (PADRE), which is applicable to arbitrary underlying learning models and operates on pairs of input data points. During training, the model learns to predict differences between all possible pairs of input points. During prediction, the test points are paired with all training set points, giving rise to a set of predictions that can be treated as a distribution of which the mean is treated as a final prediction and the dispersion is treated as an uncertainty measure. Pairwise difference regression was shown to reliably improve the performance of the random forest algorithm across five chemical ML tasks. Additionally, the pair-derived dispersion is both well correlated with model error and performs well in active learning. We also show that this method is competitive with state-of-the-art neural network techniques. Thus, pairwise difference regression is a promising tool for candidate selection algorithms used in chemical discovery.
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http://dx.doi.org/10.1021/acs.jcim.1c00670DOI Listing
August 2021

A Barium Titanate-on-Oxide Insulator Optoelectronics Platform.

Adv Mater 2021 Jul 29:e2101128. Epub 2021 Jul 29.

Department of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore, 117583, Singapore.

Electro-optic modulators are among the most important building blocks in optical communication networks. Lithium niobate, for example, has traditionally been widely used to fabricate high-speed optical modulators due to its large Pockels effect. Another material, barium titanate, nominally has a 50 times stronger r-parameter and would ordinarily be a more attractive material choice for such modulators or other applications. In practice, barium titanate thin films for optical waveguide devices are usually grown on magnesium oxide due to its low refractive index, allowing vertical mode confinement. However, the crystal quality is normally degraded. Here, a group of scandate-based substrates with small lattice mismatch and low refractive index compared to that of barium titanate is identified, thus concurrently satisfying high crystal quality and vertical optical mode confinement. This work provides a platform for nonlinear on-chip optoelectronics and can be promising for waveguide-based optical devices such as Mach-Zehnder modulators, wavelength division multiplexing, and quantum optics-on-chip.
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http://dx.doi.org/10.1002/adma.202101128DOI Listing
July 2021

Cu(II) and Cd(II) removal from aqueous solution with [email protected] and [email protected]: kinetics and probable mechanism.

Environ Sci Pollut Res Int 2021 Jul 28. Epub 2021 Jul 28.

College of Architecture and Environment, Sichuan University, Chengdu, 610065, China.

Two novel adsorbents ([email protected] and [email protected]) were successfully synthesized by grafting thiol- or amino-functionalized GO onto LDH and their adsorption capacities for heavy metal ions (Cu(II) and Cd(II)) were significantly enhanced. Characterization experiments illustrated that the thiol group (-SH) or amino group (-NH) was grafted onto [email protected] or [email protected] Adsorption isotherms were satisfactorily fitted by both Langmuir and Freundlich models. The maximum adsorption capacity of Cd(II) on [email protected] at 308 K was 102.77 mg/g, which was about triple that of [email protected] The enhancement in adsorption capacity of [email protected] was due to the cooperative effect of LDH and GO-SH. The kinetic experimental data for [email protected] and [email protected] were found to be in good agreement with the pseudo-second-order model. The thermodynamic parameters calculated from the temperature-dependent adsorption isotherms indicated that the adsorption was spontaneous and an endothermic process. The possible adsorption mechanisms comprising formation of precipitation, isomorphic substitution of Mg(II), and formation of complexation with amino groups or thiol groups were proposed. Desorption experiments put into evidence that [email protected] and [email protected] may be promising suitable candidates for the remediation of metal ions from aqueous solutions in real work in the near future.
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http://dx.doi.org/10.1007/s11356-021-15558-yDOI Listing
July 2021

Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis.

Front Nutr 2021 12;8:709683. Epub 2021 Jul 12.

Hubei Province Key Laboratory of Traditional Chinese Medicine Resource and Chemistry, Hubei University of Chinese Medicine, Wuhan, China.

Weight loss by lifestyle modification is the cornerstone therapy of non-alcoholic fatty liver disease (NAFLD). Intermittent fasting has shown favorable effects on body weight (BW) and relevant indicators of NAFLD in several reports. To estimate the effects of intermittent fasting on adults with NAFLD. Literature searches were conducted on PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov from inception to May 10, 2021. A total of six studies involving 417 patients with NAFLD were included. In the meta-analysis, there were significant differences in BW, body mass index (BMI), alanine aminotransferase (ALT), and aspartate transaminase (AST) between the control and fasting group. Up to now, there is no significant difference in triglycerides (TG), total cholesterol (TC), and other metabolic parameters between the two groups. Intermittent fasting is beneficial for weight management and liver enzyme improvement, but long-term feasibility and safety of intermittent fasting should be conducted in further studies.
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http://dx.doi.org/10.3389/fnut.2021.709683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310935PMC
July 2021

The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants.

Acta Pharmacol Sin 2021 Jul 28. Epub 2021 Jul 28.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

Androgen receptor (AR) serves as a main therapeutic target for prostate cancer (PCa). However, resistance to anti-androgen therapy (SAT) inevitably occurs. Indomethacin is a nonsteroidal anti-inflammatory drug that exhibits activity against prostate cancer. Recently, we designed and synthesized a series of new indomethacin derivatives (CZ compounds) via Pd (II)-catalyzed synthesis of substituted N-benzoylindole. In this study, we evaluated the antitumor effect of these novel indomethacin derivatives in castration-resistant prostate cancer (CRPC). Upon employing CCK-8 cell viability assays and colony formation assays, we found that these derivatives had high efficacy against CRPC tumor growth in vitro. Among these derivatives, CZ-212-3 exhibited the most potent efficacy against CRPC cell survival and on apoptosis induction. Mechanistically, CZ-212-3 significantly suppressed the expression of AR target gene networks by degrading AR and its variants. Consistently, CZ-212-3 significantly inhibited tumor growth in CRPC cell line-based xenograft and PDX models in vivo. Taken together, the data show that the indomethacin derivative CZ-212-3 significantly inhibited CRPC tumor growth by degrading AR and its variants and could be a promising agent for CRPC therapy.
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http://dx.doi.org/10.1038/s41401-021-00738-wDOI Listing
July 2021

Electric Field Control of the Magnetic Weyl Fermion in an Epitaxial SrRuO (111) Thin Film.

Adv Mater 2021 Jul 24:e2101316. Epub 2021 Jul 24.

Department of Materials Science and Engineering, National University of Singapore, Singapore, 117575, Singapore.

The magnetic Weyl fermion originates from the time reversal symmetry (TRS)-breaking in magnetic crystalline structures, where the topology and magnetism entangle with each other. Therefore, the magnetic Weyl fermion is expected to be effectively tuned by the magnetic field and electrical field, which holds promise for future topologically protected electronics. However, the electrical field control of the magnetic Weyl fermion has rarely been reported, which is prevented by the limited number of identified magnetic Weyl solids. Here, the electric field control of the magnetic Weyl fermion is demonstrated in an epitaxial SrRuO (111) thin film. The magnetic Weyl fermion in the SrRuO films is indicated by the chiral anomaly induced magnetotransport, and is verified by the observed Weyl nodes in the electronic structures characterized by the angle-resolved photoemission spectroscopy (ARPES) and first-principles calculations. Through the ionic-liquid gating experiment, the effective manipulation of the Weyl fermion by electric field is demonstrated, in terms of the sign-change of the ordinary Hall effect, the nonmonotonic tuning of the anomalous Hall effect, and the observation of the linear magnetoresistance under proper gating voltages. The work may stimulate the searching and tuning of Weyl fermions in other magnetic materials, which are promising in energy-efficient electronics.
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http://dx.doi.org/10.1002/adma.202101316DOI Listing
July 2021

Characterization, Spatial Variation and Management Strategy of Sewer Sediments Collected from Combined Sewer System: A Case Study in Longgang District, Shenzhen.

Int J Environ Res Public Health 2021 07 20;18(14). Epub 2021 Jul 20.

Department of Civil and Environmental Engineering, University of Illinois at Urbana Champaign, 205 N Mathews Ave, Urbana, IL 61820, USA.

In the urban drainage system, the formation of sewer sediments is inevitable, and the removal of sewer sediments is necessary for system maintenance. Disposal of arisings from sewer sediment removal is becoming a serious environmental issue. The current knowledge of sewer sediments is limited, which is restrained to sewer sediments management. To better understand this municipal waste, the sewer sediments of a combined sewer system in Longgang District, Shenzhen were collected and characterized, and the spatial distribution characteristics of contaminants were analyzed. Based on the bivariate correlation analysis, it is found that many contaminants in sewer sediments have a strong relationship with spatial variables. Compared to the sewer sediments in industrial areas, those in residential areas contain higher concentrations of Hg and phosphorus. The sediments in the sewage conduit also contain more organic matter (OM), phosphorus, Cu, and Ni, and the sediments in the rainwater conduit contain a higher concentration of Cd. Moreover, the sediments produced in different catchments also show huge differences in the content of contaminants. These spatial distribution characteristics may provide help for the further classification of sewer sediments, thereby making the disposal of sediments more targeted. According to the local standards of sludge disposal, land application and incineration are not suitable for managing sewer sediments due to the low OM content and poor lower heating value (LHV). Although sanitary landfill is feasible for sewer sediments disposal, the complicated composition of sewer sediments still poses the risk of polluting the surrounding environment. The management of sewer sediments via the production of building materials is a promising technical route that can avoid the migration of hazardous contaminants and produce valuable products. This study may improve our understanding of sewer sediments and provide a reliable recommendation for sewer sediment management.
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http://dx.doi.org/10.3390/ijerph18147687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303206PMC
July 2021

Blockage of Drp1 phosphorylation at Ser579 protects neurons against Aβ‑induced degeneration.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Institute of Geriatrics, Affiliated People's Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Alzheimer's disease (AD), one of the most common types of chronic neurodegenerative diseases, is pathologically characterized by the formation of amyloid β (Aβ) peptide‑containing plaques and neurofibrillary tangles. Among Aβ peptides, Aβ induces neuronal toxicity and neurodegeneration. In our previous studies, Cdk5 was found to regulate Aβ‑induced mitochondrial fission via the phosphorylation of dynamin‑related protein 1 (Drp1) at Ser579. However, whether blockage of Drp1 phosphorylation at Ser579 protects neurons against Aβ‑induced degeneration remains to be elucidated. Thus, the aim the present study was to examine the effect of mutant Drp1‑S579A on neurodegeneration and its underlying mechanism. First, the phosphorylation‑defect (phospho‑defect) mutant, Lenti‑Drp1‑S579A was constructed. Phospho‑defect Drp1‑S579A expression was detected in primary cultures of mouse cortical neurons infected with Lenti‑Drp1‑S579A using western blotting and it was found to successfully attenuate the phosphorylation of endogenous Drp1 at Ser579. In primary neuronal cultures, the neuronal processes were evaluated under microscopy. Treatment with 10 M Aβ1‑42 significantly decreased dendritic density and length, spine outgrowth and synapse number. As expected, infection of neurons with Lenti‑Drp1‑S579A efficiently alleviated the inhibitory effect of Aβ on neurite outgrowth and synapse density. In addition, infection with Lenti‑Drp1‑S579A abolished the cleavage of caspase‑3 and apoptosis in neurons exposed to Aβ. Thus, the current data demonstrated that blockage of Drp1 phosphorylation at Ser579 may be an effective strategy to protect neurons against Aβ‑induced degeneration and apoptosis. These findings underline the therapeutic potential of targeting Drp1 in the treatment of AD.
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http://dx.doi.org/10.3892/mmr.2021.12296DOI Listing
September 2021

A novel class of tsRNA signatures as biomarkers for diagnosis and prognosis of pancreatic cancer.

Mol Cancer 2021 Jul 17;20(1):95. Epub 2021 Jul 17.

Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, Chemistry and Biomedicine Innovation Center (ChemBIC), State Key Laboratory of Pharmaceutical Biotechnology and Department of Physiology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210023, China.

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http://dx.doi.org/10.1186/s12943-021-01389-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285832PMC
July 2021

Gene and protein expression profiles of olfactory ensheathing cells from olfactory bulb olfactory mucosa.

Neural Regen Res 2022 Feb;17(2):440-449

Ningxia Human Stem Cell Institute; Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.

Olfactory ensheathing cells (OECs) from the olfactory bulb (OB) and the olfactory mucosa (OM) have the capacity to repair nerve injury. However, the difference in the therapeutic effect between OB-derived OECs and OM-derived OECs remains unclear. In this study, we extracted OECs from OB and OM and compared the gene and protein expression profiles of the cells using transcriptomics and non-quantitative proteomics techniques. The results revealed that both OB-derived OECs and OM-derived OECs highly expressed genes and proteins that regulate cell growth, proliferation, apoptosis and vascular endothelial cell regeneration. The differentially expressed genes and proteins of OB-derived OECs play a key role in regulation of nerve regeneration and axon regeneration and extension, transmission of nerve impulses and response to axon injury. The differentially expressed genes and proteins of OM-derived OECs mainly participate in the positive regulation of inflammatory response, defense response, cytokine binding, cell migration and wound healing. These findings suggest that differentially expressed genes and proteins may explain why OB-derived OECs and OM-derived OECs exhibit different therapeutic roles. This study was approved by the Animal Ethics Committee of the General Hospital of Ningxia Medical University (approval No. 2017-073) on February 13, 2017.
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http://dx.doi.org/10.4103/1673-5374.317986DOI Listing
February 2022

Determination of nutrient profile in plant materials using laser-induced breakdown spectroscopy with partial least squares-artificial neural network hybrid model: erratum.

Opt Express 2021 Jun;29(13):20687

We provide corrected funding number for the previous publication [Opt. Express28, 23037 (2020)10.1364/OE.399909].
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http://dx.doi.org/10.1364/OE.432474DOI Listing
June 2021

Decoupling control algorithm based on numerical orthogonal polynomials for a woofer-tweeter adaptive optics system.

Opt Express 2021 Jul;29(14):22331-22344

To resolve cooperative control issues of dual wavefront correctors in generalized irregular pupil regions, we propose a decoupling control algorithm based on numerical orthogonal polynomials (NOP). The proposed algorithm firstly deduces NOP from Zernike polynomials in generalized irregular pupil regions. Then, according to wavefront restoration, different spatial frequency aberrations to different wavefront correctors are assigned precisely. Finally, the algorithm calculates and eliminates the cross-coupling between dual wavefront correctors. As observed in numerical simulations and experiments based on a typical woofer-tweeter (W-T) adaptive optics system, NOP decoupling control algorithm restrains the cross-coupling between woofer and tweeter in generalized irregular pupil regions. Moreover, there are obvious advantages over Zernike polynomials decoupling control algorithm in cross-coupling suppression for various scenarios in irregular pupil regions and restoration orders.
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http://dx.doi.org/10.1364/OE.426905DOI Listing
July 2021

diagnosis of mature HLB-asymptomatic citrus fruits by laser-induced breakdown spectroscopy.

Appl Opt 2021 Jul;60(20):5846-5853

Laser-induced breakdown spectroscopy (LIBS) is a promising alternative to conventional methods in classifying citrus huanglongbing (HLB). Mature citrus fruits with similar features were picked and divided into healthy and HLB-asymptomatic groups. LIBS spectra and images were collected by focusing a laser on fresh fruit surfaces without sample preparation. The pH value and soluble solids content of juice as the indicators of acidity and sugar were detected, and the content of Ca, Zn, and K in peel and pulp was analyzed. The characteristic lines from LIBS spectra were extracted by continuous wavelet transform and principal component analysis (PCA). The -test of these indicators displayed significant difference between the two groups. Fisher discriminant analysis and multilayer perception neural network (MLP) were applied to identify the disease. The classification accuracy reached 100% by PCA-MLP. The results show that LIBS can realize in situ detection of citrus HLB fruits.
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http://dx.doi.org/10.1364/AO.427856DOI Listing
July 2021

Contribution of Different Phenotypes of Obesity to Metabolic Abnormalities from a Cross-Sectional Study in the Northwest China.

Diabetes Metab Syndr Obes 2021 7;14:3111-3121. Epub 2021 Jul 7.

Department of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, Yinchuan, Ningxia, People's Republic of China.

Background: This study has been conducted to explore the correlation between phenotypes of obesity and metabolic comorbidities.

Methods: This cross-sectional study recruited 14,724 adults aged ≥18 years with a randomized stratified sampling strategy. Obesity was classified into four types according to body mass index (BMI) and waist-to-height ratio (WHtR): normal weight with central obesity (NWCO) and without (NW) CO, and obese or overweight with (OBCO) and without (OB) central obesity. Uric acid (UA), fasting blood glucose (FBG), and lipid profile were measured.

Results: The prevalence of hyperuricemia in the 4 groups (NW, NWCO, OB and OBCO) was 3.7%, 5.6%, 8.7% and 12.4%, whilst the prevalence of hypertriglyceridemia was 13.4%, 27.4%, 30.3% and 43.7%, separately. The prevalence of hypo-high-density lipoprotein cholesterolemia (hypo-HDL emia) was 20.1%, 21.4%, 30.8% and 27.9%, while the prevalence of hyper-low-density lipoprotein cholesterolemia (hyper-LDL emia) was 9.8%, 24.4%, 12.3% and 27.9%. The prevalence of hypercholesterolemia was 11.2%, 23.5%, 14.7%, 28.5% and the prevalence of hyperglycemia was 9.7%, 22.6%, 18.5%, and 27.0%, respectively. The prevalence of hypertension was 6.9%, 13.1%, 14.7%, and 20.6%. For various metabolic abnormalities, OBCO have the highest risks compared with NW (hyperuricemia: adjusted OR (aOR)= 2.60; hypertriglyceridemia: aOR= 3.19; hypercholesterolemia: aOR= 1.48; hyper LDLemia: aOR= 2.21; hypo HDLemia: aOR= 1.42; hyperglycemia: aOR= 1.95; hypertension: aOR= 2.16). The risk of hyper LDLemia, hypercholesterolemia and hyperglycemia in the NWCO group was higher than that in the OB group (hyperLDLemia: aOR: 1.69 vs 0.97; hypercholesterolemia: aOR: 1.27 vs 1.24; hyperglycemia: aOR: 1.62 vs 1.28).

Conclusion: Different phenotypes of obesity are significantly associated with metabolic abnormalities. NWCO is more closely associated with hypercholesterolemia, hyperglycemia and hyper LDLemia. General obesity and central obesity have a synergistic effect on the diseases.
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http://dx.doi.org/10.2147/DMSO.S314935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273743PMC
July 2021

Citrus alkaline extracts prevent endoplasmic reticulum stress in type II alveolar epithelial cells to ameliorate pulmonary fibrosis via the ATF3/PINK1 pathway.

Phytomedicine 2021 Aug 21;89:153599. Epub 2021 May 21.

Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address:

Background: Idiopathic pulmonary fibrosis is a chronic, progressive, fibrotic disease. Although the pathogenesis remains unclear, the effect of endoplasmic reticulum (ER) stress in type II alveolar epithelial cells (AEC IIs) is increasingly thought to be a critical mechanism.

Purpose: We investigated the effects of citrus alkaline extracts (CAE) on AEC IIs and elucidated the underlying mechanism for their possible use in ameliorating pulmonary fibrosis (PF).

Methods: A bleomycin-induced mouse model of PF, and an in vitro tunicamycin (TM) -induced ER stress model in A549 cells were successfully established. Accumulation of collagen in lung tissues in vivo was assessed using histological analysis and western blotting. The expression levels of the ER-stress marker BiP and other related proteins were assessed by western blotting and immunofluorescence staining. Mitochondrial membrane potential was assessed to evaluate mitochondrial homeostasis.

Results: CAE mitigated collagen deposition to ameliorate PF in vivo. CAE suppressed the bleomycin or TM-induced increases in ER-stress biomarker, BiP, and PERK pathway proteins, resulting in a decrease in ER stress in mouse lung tissues and A549 cells, respectively. Additionally, CAE treatment suppressed the bleomycin or TM-induced increase in the ER-stress downstream proteins, activating ATF3 and increased the levels of PINK1 in AEC IIs, both in vivo and in vitro. The reduced mitochondrial homeostasis induced by TM was restored by CAE-treatment in A549 cells. Furthermore, conditioned media from TM-treated A549 cells increased collagen deposition in MRC5 cells mainly via TGF-β1. The increased collagen deposition was not seen using conditioned media from CAE-treated A549 cells.

Conclusion: These results provide novel insights into the potential mechanism of CAE in inhibiting ER stress in AEC IIs, and suggests that it has great potential to ameliorate PF via the ATF3/PINK1 pathway.
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http://dx.doi.org/10.1016/j.phymed.2021.153599DOI Listing
August 2021

Cardiac Shock Wave Therapy Improves Ventricular Function by Relieving Fibrosis Through PI3K/Akt Signaling Pathway: Evidence From a Rat Model of Post-infarction Heart Failure.

Front Cardiovasc Med 2021 16;8:693875. Epub 2021 Jun 16.

Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Cumulative studies have identified the effectiveness of cardiac shock wave therapy (CSWT) in treating heart failure after acute myocardial infarction (AMI), but little have been discussed with regard to the beneficial effects of CSWT on anti-fibrosis along with the underlying mechanism. In this study, we investigated whether CSWT could reduce post-AMI fibrosis and further explored the molecular mechanism. Rat heart failure (HF) models induced by ligating the left anterior descending coronary artery were established and validated by echocardiography. Eligible animals were randomly categorized into five groups: the sham group, the HF group, the HF + CSWT group, the HF + LY294002 group, and the HF + CSWT + LY294002 group. The cardiac weight, serum level of BNP, NT-pro BNP and echocardiography parameters were measured to assess cardiac function in different groups. Masson's trichrome staining was used to assess the proportions of the fibrotic area. The expression level of CD34, αSMA was measured by RT-PCR, Immunohistochemistry and Immunofluorescent analyses and the level of PI3K/Akt was quantified by Immunohistochemistry and Western blotting. The application of CSWT significantly improved cardiac function and reduced myocardial fibrosis and level of CD34 and αSMA, compared to the HF group. CSWT led to significant elevations of p-PI3K and p-Akt expression levels compared to that of the HF group and the inhibition of the PI3K/Akt pathway abolished the observed beneficial effects of CSWT. CSWT can facilitate the alleviation of cardiac fibrosis induced by AMI through the activation of PI3K/Akt signaling pathway.
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http://dx.doi.org/10.3389/fcvm.2021.693875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241915PMC
June 2021

GJA1 rs2071165 A > G Variant Increased Gastric Cancer Risk in Females of Northwest China: A Case-Control Study.

J Oncol 2021 19;2021:5556303. Epub 2021 May 19.

Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an 710032, China.

Gastric cancer (GC) is one of the most common malignancies, and its incidence rates vary widely between men and women. Previous studies have suggested that connexin 43 (Cx43, encoded by gap junction protein alpha 1 (GJA1)) and secretory carrier membrane protein 1 (SCAMP1) are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated. A total of three single-nucleotide polymorphisms among 681GC patients and 756 controls were tested using the Agena MassARRAY RS1000 system, including GJA1 rs2071165, SCAMP1 rs4530741, and SCAMP1 rs6874309. The strength of the association with GC risk was assessed by the odds ratios (ORs) and 95% confidence intervals (CIs) generated from the logistic regression model. Kaplan-Meier curve, long-rank tests, and a multivariate Cox proportional hazard model were used for prognosis analysis. The expression of GJA1 was assessed by immunohistochemistry. The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (OR = 1.55, 95% CI = 1.03-2.32, =0.034). Furthermore, the risk effect of GJA1 rs2071165 was more evident in the subgroups of female patients with GC, stratified by age, clinical stage, tumor size, and recurrence/metastasis. However, no obvious differences in Cx43 expression in GC tissues were observed between males and females. Furthermore, no significant association between SCAMP1 rs4530741 and rs6874309 polymorphisms and GC risk or prognosis was observed. In conclusion, this study suggests for the first time that the GJA1 rs2071165 polymorphism is associated with increased GC risk in females, revealing a potential new clinical marker for assessing GC risk in females.
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http://dx.doi.org/10.1155/2021/5556303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225425PMC
May 2021

Wavefront Restoration Technology of Dynamic Non-Uniform Intensity Distribution Based on Extreme Learning Machine.

Sensors (Basel) 2021 Jun 4;21(11). Epub 2021 Jun 4.

Key Laboratory on Adaptive Optics, Chinese Academy of Sciences, Chengdu 610209, China.

Non-uniform intensity distribution of laser near-field beam results in the irregular shape of the spot in the wavefront sensor. The intensity of some sub-aperture spots may be too weak to be detected, and the accuracy of wavefront restoration is seriously affected. Therefore, an extreme learning machine method is proposed to realize high precision wavefront restoration under dynamic non-uniform intensity distribution. The simulation results show that this method has better accuracy of wavefront restoration than the classical modal algorithm under dynamic non-uniform intensity distribution. The root mean square error of the residual wavefront for the proposed method is only 2.9% of the initial value.
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http://dx.doi.org/10.3390/s21113877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200106PMC
June 2021

Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial.

J Clin Oncol 2021 Jun 29:JCO2100163. Epub 2021 Jun 29.

School of Public Health, Nanjing Medical University, Nanjing, China.

Purpose: Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC.

Patients And Methods: This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients.

Results: Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 3.6 months ( .0570). The objective response rate was 4.6% 2.7% ( = .2448), and the disease control rate was 30.8% 28.7% (FAS; = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] 165 [50%]; .0018).

Conclusion: Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.
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http://dx.doi.org/10.1200/JCO.21.00163DOI Listing
June 2021

MoSSe Nanosheets Grown on Hollow Carbon Spheres for Enhanced Electrochemical Activity.

Langmuir 2021 Jul 25;37(27):8314-8322. Epub 2021 Jun 25.

School of Material Science and Engineering, University of Jinan, Jinan 250022, PR China.

Electrochemical catalysts with high conductivity and low reaction potential are respected. In this paper, hollow carbon spheres (HCSs) were homogeneously coated with Se-doped MoS (MoSSe) nanosheets by hydrothermal synthesis. The HCSs reduced the agglomeration of MoSSe nanosheets and improved their conductivity. Compared with the MoS-modified samples, Se doping increased the interlayer spacing which provided more active catalytic sites and improved the charge transfer. Thus, MoSSe-decorated samples revealed enhanced electrocatalytic activity. The composition of MoSSe nanosheets was adjusted by changing the ratios of sulfur and selenium precursors. In the case of a Se/S molar ratio of 0.1, the composite of HCS decorated with MoSSe nanosheets ([email protected]) revealed the lowest overpotential and the smallest Tafel slope.
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http://dx.doi.org/10.1021/acs.langmuir.1c01122DOI Listing
July 2021

Concomitant acute myocardial infarction and acute pulmonary embolism caused by paradoxical embolism: a case report.

BMC Cardiovasc Disord 2021 Jun 24;21(1):313. Epub 2021 Jun 24.

Department of Cardiology, China-Japan Union Hospital of Jilin University, Xiantai Street No. 126, Changchun, 130031, Jilin, China.

Background: Due to its low incidence and diverse manifestations, paradoxical embolism (PDE) is still under-reported and is not routinely considered in differential diagnoses. Concomitant acute myocardial infarction (AMI) and acute pulmonary embolism (PE) caused by PDE has rarely been reported.

Case Presentation: A 45-year-old woman presented with acute chest pain and difficulty with breathing. Multiple imaging modules including ECG, echocardiography, emergency cardioangiogram (CAG), and CT angiography of the pulmonary arteries showed acute occlusion of the posterolateral artery and acute PE. After coronary aspiration, no residual stenosis was observed. One month later, a bubble study showed inter-atrial communication via a patent foramen ovale (PFO). The AMI in this patient was finally attributed to PDE via the PFO. PFO closure was performed, and long-term anticoagulation was prescribed to prevent recurrent thromboembolic events.

Conclusions: PDE via PFO is a rare etiology of AMI, especially in patients with concomitant AMI and PE. Clinicians should be vigilant of this possibility and close the inter-atrial channel for secondary prevention.
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http://dx.doi.org/10.1186/s12872-021-02123-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223270PMC
June 2021

Near-infrared laparoscopy with indocyanine green for axillary sentinel lymph node biopsy in early breast cancer: preliminary experience of a single unit.

Gland Surg 2021 May;10(5):1677-1686

Department of General Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, China.

Background: A sentinel lymph node biopsy (SLNB) is a routine procedure for axillary staging in cN0 breast cancer (BC) patients. Indocyanine green (ICG) fluorescence can detect sentinel lymph nodes with higher sensitivity than carbon nanoparticle suspension (CNS). The present study investigated the availability and benefits of a near-infrared (NIR) laparoscopy-assisted SLNB using ICG and carbon nanoparticle suspension as tracers.

Methods: Forty patients with invasive BC, who had clinically negative axillary lymph nodes, participated in this observational study. ICG and CNS tracers were injected into the periareolar region simultaneously or sequentially. In the endoscopy-assisted group (n=20), the patients were given NIR laparoscopic SLNB based on ICG fluorescence and CNS staining. In the open-surgery group, the patients were given traditional SLNB using an open incision, and CNS tracers were injected into the same region as that in the endoscopy-assisted group.

Results: In the endoscopy-assisted group, lymphatic vessels and sentinel lymph nodes (SLNs) were successfully identified using ICG fluorescence imaging in most patients (19/20). The average number of SLNs removed was 2.85 (range, 1-4) in the endoscopy-assisted group, and 3.40 (range, 1-7) in the open-surgery group. There was no significant difference between the number of detected nodes (P=0.30). The patients who underwent endoscopy-assisted SLNBs had similar operating times, blood loss and hospital-stay lengths, but lower postoperative drainage volumes and higher satisfaction scores, as they did not have axillary incisions.

Conclusions: The NIR laparoscopy-assisted ICG-guided technique is a feasible and surgeon-friendly method for SLNB with good efficacy and acceptable safety. When combined with CNS, more SLNs can be detected and dissected.
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http://dx.doi.org/10.21037/gs-21-223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184382PMC
May 2021

Modulation of Spin-Orbit Torque from SrRuO by Epitaxial-Strain-Induced Octahedral Rotation.

Adv Mater 2021 Jul 19;33(30):e2007114. Epub 2021 Jun 19.

Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore, 117575, Singapore.

Spin-orbit torque (SOT), which arises from the spin-orbit coupling of conduction electrons, is believed to be the key route for developing low-power, high-speed, and nonvolatile memory devices. Despite the theoretical prediction of pronounced Berry phase curvatures in certain transition-metal perovskite oxides, which lead to considerable intrinsic spin Hall conductivity, SOT from this class of materials has rarely been reported until recently. Here, the SOT generated by epitaxial SrRuO of three different crystal structures is systematically studied. The results of both spin-torque ferromagnetic resonance and in-plane harmonic Hall voltage measurements concurrently reveal that the intrinsic SOT efficiency of SrRuO decreases when the epitaxial strain changes from tensile to compressive. The X-ray diffraction data demonstrate a strong correlation between the magnitude of SOT and octahedral rotation around the in-plane axes of SrRuO , consistent with the theoretical prediction. This work offers new possibilities of tuning SOT with crystal structures and novel opportunities of integrating the unique properties of perovskite oxides with spintronic functionalities.
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http://dx.doi.org/10.1002/adma.202007114DOI Listing
July 2021

Ferroelectric Self-Polarization Controlled Magnetic Stratification and Magnetic Coupling in Ultrathin LaSrMnO Films.

ACS Appl Mater Interfaces 2021 Jun 17;13(25):30137-30145. Epub 2021 Jun 17.

Department of Materials Science & Engineering, National University of Singapore, Singapore 117575, Singapore.

Multiferroic oxide heterostructures consisting of ferromagnetic and ferroelectric components hold the promise for nonvolatile magnetic control via ferroelectric polarization, advantageous for the low-dissipation spintronics. Modern understanding of the magnetoelectric coupling in these systems involves structural, orbital, and magnetic reconstructions at interfaces. Previous works have long proposed polarization-dependent interfacial magnetic structures; however, direct evidence is still missing, which requires advanced characterization tools with near-atomic-scale spatial resolutions. Here, extensive polarized neutron reflectometry (PNR) studies have determined the magnetic depth profiles of PbZrTiO/LaSrMnO (PZT/LSMO) bilayers with opposite self-polarizations. When the LSMO is 2-3 nm thick, the bilayers show two magnetic transitions on cooling. However, temperature-dependent magnetization is different below the lower-temperature transition for opposite polarizations. PNR finds that the LSMO splits into two magnetic sublayers, but the inter-sublayer magnetic couplings are of opposite signs for the two polarizations. Near-edge X-ray absorption spectroscopy further shows contrasts in both the Mn valences and the Mn-O bond anisotropy between the two polarizations. This work completes the puzzle for the magnetoelectric coupling model at the PZT/LSMO interface, showing a synergic interplay among multiple degrees of freedom toward emergent functionalities at complex oxide interfaces.
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http://dx.doi.org/10.1021/acsami.1c02300DOI Listing
June 2021

Plasma Amino Acids and Residual Hypertriglyceridemia in Diabetic Patients Under Statins: Two Independent Cross-Sectional Hospital-Based Cohorts.

Front Cardiovasc Med 2021 31;8:605716. Epub 2021 May 31.

Cardiology Department, China-Japan Union Hospital of Jilin University, Changchun, China.

The objective of the study was to investigate the relationship of amino acid metabolism with hypertriglyceridemia in diabetic patients under statins free of prior cardiovascular diseases. Two independent cross-sectional hospital based cohorts, i.e., Liaoning Medical University First Affiliated Hospital (LMUFAH, = 146) and the Second Affiliated Hospital of Dalian Medical University (SAHDMU, = 294) were included in the current analysis. Hypertriglyceridemia was defined as triglyceride ≥1.7 mmol/L, and well-controlled LDL-C was defined as <2.6 mmol/L. The adjusted ORs (95% CI) of circulating metabolic measures for hypertriglyceridemia were assessed using logistic regression. Pooled results of metabolites with the same direction of association in both cohorts were combined using inverse variance-weighted fixed-effect meta-analysis. Difference of identified metabolites in patients with and without hypertriglyceridemia were also obtained in the context of LDL-C. Patients, 86 and 106, were with hypertriglyceridemia in LMUFAH and SAHDMU, respectively. We observed that elevated alanine, asparagine, leucine, and valine were consistently associated with increased hypertriglyceridemia in both cohorts. In fixed-effect pooled analysis, the OR (95% CI) per SD increase was 1.71 (1.32-2.20) for alanine, 1.62 (1.20-2.19) for asparagine, 1.64 (1.22-2.20) for leucine, and 1.62 (1.22-2.13) for valine (all values ranged from 0.0018 to <0.0001); adjusting for C-peptide attenuated effect sizes of Ala, Leu, and Val for hypertriglyceridemia. The difference were robust in groups with well- or bad-controlled LDL-C. Among 23 amino acids, alanine, asparagine, leucine, and valine were positively associated with increased residual risk of hypertriglyceridemia in diabetic patients with statin treatment.
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http://dx.doi.org/10.3389/fcvm.2021.605716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200824PMC
May 2021

Side effects of CDK4/6 inhibitors in the treatment of HR+/HER2- advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Ann Palliat Med 2021 May;10(5):5590-5599

Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.

Background: Although combination of cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors with endocrine therapy for advanced breast cancer (ABC) prolongs PFS in patients, but also has associated toxic side effects. However, few previous studies have summarized the toxic and side effects of CDK4/6 inhibitors. Therefore, this study summarized the corresponding toxic and side effects of CDK/6 inhibitors, which is of great importance for doctors and patients to understand how to balance the high survival rate brought by drugs with the decreased quality of life and improve the management of BC.

Methods: PubMed, Embase, The Cochrane Library, and VIP databases were systematically searched to collect randomized controlled trials (RCTs) of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from January 2010 to December 2019.Two investigators independently reviewed the literatures. Before using the RevMan 5.3 software for a meta-analysis, date were extracted and the risk of bias with the include studies were assessed.

Results: A total of 64 RCTs involving 3685 patients were included. Compared with placebo combined with endocrine therapy, CDK4/6 inhibitors combined with endocrine therapy could improve the median progression free survival rate (hazard ratio 0.54, 95% confidence interval (CI):0.50-0.60, P<0.00001). In terms of adverse reactions, CDK4/6 inhibitors combined with endocrine therapy had higher rates of neutropenia, leukopenia, thrombocytopenia, anemia, fatigue, diarrhea, febrile neutropenia, nausea and increased alanine aminotransferase (ALT).

Discussion: CDK4/6 inhibitors have strong specification in the treatment of ABC because of their role in regulating the cell cycle. Although CDK4/6I combined with endocrine therapy can improve the effective rate and median PFS of patients with HR+/HER2-ABC, this treatment regimen increases the incidence of adverse reactions such as neutropenia, leukopenia, thrombocytopenia, anemia, fatigue, diarrhea, febrile neutropenia, nausea and increased ALT. Further research into improving the survival rate while reducing or even avoiding the side effects of CDK4/6Isis needed for better clinical management of BC.

Trial Registration: PROSPERO (CRD42020171112).
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http://dx.doi.org/10.21037/apm-21-1096DOI Listing
May 2021

MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2.

Am J Cancer Res 2021 15;11(5):2159-2173. Epub 2021 May 15.

Department of Oncology, Affiliated Eighth People's Hospital, Jiangsu University Shanghai, China.

MiR-22 has been demonstrated to inhibits tumor growth in several cancers. However, its function in the tumor microenvironment is still unclear, especially for T cell differentiation. Here, miR-22 expression in the circulating T cells from hepatocellular carcinoma (HCC) patients and healthy controls was analyzed with quantitative polymerase chain reaction (qPCR). Diethylnitrosamine (DEN)/phenobarbital (PB)-mediated primary HCC and Hepa1-6 subcutaneous tumor mouse models were established and subjected to lenti-miR-22 injection. Mice immunoreconstituted with miR-22-overexpressing T cells were employed to investigate the antitumor effect of miR-22 in mice. Luciferase assay, immunofluorescent staining, in vitro Th17 cell differentiation assay, and rescue experiments were employed to investigate the mechanism underlying the miR-22-mediated regulation of Th17 cell differentiation and liver tumor growth. Results confirmed the dramatic downregulation of miR-22 expression in malignant tissues and circulating T cells from patients with HCC. MiR-22 expression correlated with good prognosis of patients. Overexpression of miR-22 impaired the DEN/PB-induced primary HCC formation and the growth of Hepa1-6 subcutaneous tumors by promoting Th17 differentiation. Injection of miR-22-overexpressing T cells in irradiated mice resulted in the inhibition of Hepa1-6 subcutaneous tumor growth via Th17 differentiation promotion. MiR-22 could directly bind to Jarid2, which played an important role during the miR-22-mediated regulation of Th17 differentiation. Taken together, our study expands the understanding of miR-22 function and provides a therapy target for HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167680PMC
May 2021

Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice.

Aging Dis 2021 Jun 1;12(3):747-763. Epub 2021 Jun 1.

1Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Atherosclerosis is a serious age-related pathology, and one of its hallmarks is the presence of chronic inflammation. Sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) is a cholesterol sensor that plays an essential role in regulating intracellular cholesterol homeostasis. Accordingly, dysregulation of the SCAP-SREBP pathway has been reported to be closely associated with an increased risk of obesity, hypercholesterolemia, and cardiovascular disease. In this study, we explored whether sterol-resistant SCAP (D443N mutation) in vascular smooth muscle cells (VSMCs) of mice promotes vascular inflammation and accelerates the occurrence and progression of atherosclerosis. We established a transgenic knock-in mouse model of atherosclerosis with an activating D443N mutation at the sterol-sensing domain of SCAP (SCAP) by microinjection. Next, SCAP/ApoE mice were generated by crossing SCAP mice with apolipoprotein E (ApoE) background mice. We found that sterol-resistant SCAP markedly amplified and accelerated the progression of atherosclerotic plaques in SCAP/ApoE mice compared with that in control ApoE mice. Similarly, in SCAP mice, aortic atherosclerotic plaques both appeared earlier and were greater in number than that in control SCAP mice, both of which were fed a Western diet for 12 or 24 weeks. Moreover, we observed that sterol-resistant SCAP significantly increased local inflammation and induced endothelial dysfunction in the aortas of SCAP mice and SCAP/ApoE mice. , we also found that sterol-resistant SCAP overexpression in VSMCs increased the release of inflammatory cytokines and induced endothelial cell injury when both cell types were cocultured. Furthermore, we demonstrated that sterol-resistant SCAP overexpression in VSMCs promoted SCAP and NLRP3 inflammasome cotranslocation to the Golgi and increased the activation of the NLRP3 inflammasome pathway. These findings suggested that sterol-resistant SCAP in VSMCs of mice induced vascular inflammation and endothelial dysfunction, consequently accelerating atherosclerosis by activating the NLRP3 inflammasome pathway.
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http://dx.doi.org/10.14336/AD.2020.1120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139202PMC
June 2021

Coastal reservoirs as a source of nitrous oxide: Spatio-temporal patterns and assessment strategy.

Sci Total Environ 2021 May 21;790:147878. Epub 2021 May 21.

School of Geographical Sciences, Fujian Normal University, Fuzhou 350007, China.

Coastal reservoirs are widely regarded as a viable solution to the water scarcity problem faced by coastal cities with growing populations. As a result of the accumulation of anthropogenic wastes and the alteration of hydroecological processes, these reservoirs may also become the emission hotspots of nitrous oxide (NO). Hitherto, accurate global assessment of NO emission suffers from the scarcity and low spatio-temporal resolution of field data, especially from small coastal reservoirs with high spatial heterogeneity and multiple water sources. In this study, we measured the surface water NO concentrations and emissions at a high spatial resolution across three seasons in a subtropical coastal reservoir in southeastern China, which was hydrochemically highly heterogeneous because of the combined influence of river runoff, aquacultural discharge, industrial discharge and municipal sewage. Both NO concentration and emission exhibited strong spatio-temporal variations, which were correlated with nitrogen loading from the river and wastewater discharge. The mean NO concentration and emission were found to be significantly higher in the summer than in spring and autumn. The results of redundancy analysis showed that NH-N explained the greatest variance in NO emission, which implied that nitrification was the main microbial pathway for NO production in spite of the potentially increasing importance of denitrification of NO-N in the summer. The mean NO emission across the whole reservoir was 107 μg m h, which was more than an order of magnitude higher than that from global lakes and reservoirs. Based on our results of Monte Carlo simulations, a minimum of 15 sampling points per km would be needed to produce representative and reliable NO estimates in such a spatially heterogeneous aquatic system. Overall, coastal reservoirs could play an increasingly important role in future climate change via their NO emission to the atmosphere as water demand and anthropogenic pressure continue to rise.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147878DOI Listing
May 2021
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