Publications by authors named "Tingting Zhao"

452 Publications

Trends in Piezo Channel Research Over the Past Decade: A Bibliometric Analysis.

Front Pharmacol 2021 15;12:668714. Epub 2021 Apr 15.

Department of Acupuncture Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

We used bibliometric methods to evaluate the global scientific output of research on Piezo channels and explore the current status and trends in this field over the past decade. Piezo channel-related studies published in 2010-2020 were retrieved from Web of Science. The R bibliometrix package was used for quantitative and qualitative analyses of publication outputs and author contributions. VOSviewer was used to construct networks based on co-authorship of countries/institutions/authors, co-citation analysis of journals/references, citation analysis of documents, and co-occurrence of keywords. In total, 556 related articles and reviews were included in the final analysis. The number of publications has increased substantially with time. The country and institution contributing the most to this field was the United States and Scripps Research Institute, respectively. Ardem Patapoutian was the most productive author and ranked first among the cited authors, -index, and -index. The top cited reference was the article published by Coste B et al. in (2010) that identified Piezo1/2 in mammalian cells. The top journals in terms of the number of selected articles and citations were and , respectively. The co-occurrence analysis revealed that Piezo channels are involved a variety of cell types (Merkel cells, neurons, endothelial cells, red blood cells), physiological processes (touch sensation, blood pressure, proprioception, vascular development), related ion channels (transient receptor potential, Gardos), and diseases (pain, distal arthrogryposis, dehydrated hereditary stomatocytosis, cancer), and pharmacology (Yoda1, GsMTx-4). Our bibliometric analysis shows that Piezo channel research continues to be a hotspot. The focus has evolved from Piezo identification to architecture, activation mechanism, roles in diseases, and pharmacology.
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http://dx.doi.org/10.3389/fphar.2021.668714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082452PMC
April 2021

MoS/FeS Nanocomposite Catalyst for Efficient Fenton Reaction.

ACS Appl Mater Interfaces 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, University of California, Riverside California 92521 United States.

Nanocomposites containing FeS as catalyst and MoS as cocatalyst have been synthesized toward efficient heterogeneous Fenton reaction. The deposition of FeS nanoparticles in situ on the surface of MoS nanosheets creates strong contact between the two components and generates a large number of exposed Mo sites and sulfur vacancies, which contribute to the enhanced degradation rate by accelerating Fe/Fe cycling and ensuring rapid electron transfer. In addition, the MoS/FeS nanocomposite catalysts exhibit the best performance at near-neutral conditions (pH 6.5), which solves the challenges in conventional Fenton reactions such as leaching of metal ions, the formation of iron slurry, and the need of adjusting solution pH. Further, the nanocomposite can maintain high efficiency after many recycling experiments. It is believed that the MoS/FeS nanocomposite represents an efficient heterogeneous Fenton catalyst that can greatly promote the performance of advanced oxidation processes (AOPs) for solving practical environmental issues.
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http://dx.doi.org/10.1021/acsami.1c02864DOI Listing
April 2021

Gas-solid interfacial charge transfer in volatile organic compound detection by CuCrOnanoparticles.

Nanotechnology 2021 May 10;32(31). Epub 2021 May 10.

Key Laboratory of Advanced Display and System Applications of Ministry of Education, Shanghai University, 149 Yanchang Road, Shanghai, 200072, People's Republic of China.

Nanostructured metal oxide semiconductors have received great attention used as the chemiresistive layer of gas sensor to detect the volatile organic compound recently. As indispensable complementary parts for dominative n-type semiconductors, the p-type metal oxides based gas sensors fail to be studied sufficiently, which hampers their practical applications. In this work, the p-type delafossite CuCrOnanoparticles were synthesized, characterized, and tested for gas sensing, followed by the first principles calculations to simulate the generation of chemiresistive signal. The hydrothermal synthesis time of CuCrOnanoparticles is optimized as 24 h with a higher proportion of oxygen vacancies but a smaller size, which is confirmed by the microscopy and spectrum characterization and allows for a prevailing gas sensitivity. Meanwhile, this CuCrOgas sensor is proven to perform a higher selectivity to n-propanol and a low detection limit of 1 ppm. The adsorption sites and charge variations of dehydrogenation at the gas-solid interface predicted by the theoretical analysis are claimed to be crucial to such selectivity. It is an innovative approach to understand the chemiresistive gas sensing by evaluating the preference of charge transfer between the sensor and target gaseous molecule, which provides a new route to precisely design and develop the advanced sensing devices for the diverse applications.
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http://dx.doi.org/10.1088/1361-6528/abfa55DOI Listing
May 2021

Comprehensive Analysis of the Control of Cancer Stem Cell Characteristics in Endometrial Cancer by Network Analysis.

Comput Math Methods Med 2021 29;2021:6653295. Epub 2021 Mar 29.

Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital, Sun Yat-sen University, China.

Background: Cancer stem cells play an important role in endometrial cancer (EC). It is closely related to self-renewal and therapeutic resistance of EC.

Methods: In this study, WGCNA (weighted gene coexpression network analysis) was used to analyze the relationship between genes and clinical features. We also performed immune cell infiltration analysis of a key module by using ImmuCellAI (Immune Cell Abundance Identifier). Then, key genes were verified in the GEO database. Finally, causal relationship analysis and protein-protein interaction analysis were performed in DisNor tool and STRING.

Result: The mRNA expression-based stemness index (mRNAsi) is significantly lower in normal tissues and is significantly higher in individuals with stage IV or high-grade cancer and those who are obese or postmenopausal. Nineteen key genes (ORC6, C1orf112, RAD54L, SGO2, BUB1, PLK4, KIF18B, BUB1B, TTK, NCAPG, XRCC2, CENPF, KIF15, RACGAP1, ARHGAP11A, TPX2, KIF14, KIF4A, and NCAPH) that were enriched mainly in terms related to the cell cycle and DNA replication were selected by weighted gene coexpression network analysis (WGCNA). Based on the key modules, the numbers of NKT cells, NK cells, and neutrophils in the normal group were significantly higher than those in the cancer group. PLK1, CDK1, and MAD2L1, which were correlated with upstream genes, may be an regulated upstream of key genes.

Conclusion: PLK1, CDK1, and MAD2L1 which were strongly correlated with upstream genes may be a regulated upstream of key genes.
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http://dx.doi.org/10.1155/2021/6653295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025127PMC
March 2021

Vitexin exerts protective effects against calcium oxalate crystal-induced kidney pyroptosis in vivo and in vitro.

Phytomedicine 2021 Jun 29;86:153562. Epub 2021 Mar 29.

Department of Nephrology, Changhai Hospital, Naval Medical University, Shanghai 200433, PR China. Electronic address:

Background: Nephrolithiasis is a common urinary disease with a high recurrence rate of secondary stone formation. Several mechanisms are involved in the onset and recurrence of nephrolithiasis, e.g., oxidative stress, inflammation, apoptosis, and epithelial-mesenchymal transition (EMT). Vitexin, a flavonoid monomer derived from medicinal plants that exert many biological effects including anti-inflammatory and anticancer effects, has not been investigated in nephrolithiasis studies. Moreover, pyroptosis, a form of programmed cell death resulting from inflammasome-associated caspase activation, has not been studied in mice with nephrolithiasis.

Purpose: We aimed to investigate the protective effect and underlying mechanisms of vitexin in nephrolithiasis, and the related role of pyroptosis in vivo and in vitro.

Methods: Mouse models of nephrolithiasis were established via intraperitoneal injection of glyoxylate, and cell models of tubular epithelial cells and macrophages were established using calcium oxalate monohydrate (COM). Crystal deposition and kidney tissue injury were evaluated by hematoxylin and eosin, and von Kossa staining. Renal oxidative stress indexes including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), were analyzed. The renal expression of interleukin-1 beta (IL-1β), gasdermin D (GSDMD), osteopontin (OPN), CD44, and monocyte chemotactic protein 1 (MCP-1), and EMT-related proteins in renal tubular epithelial cells was assessed. Cell viability and the apoptosis ratio were evaluated.

Results: In vivo, vitexin alleviated crystal deposition and kidney tissue injury, and decreased the level of MDA, and increased the levels of SOD, GSH, and CAT. Vitexin also reduced the levels of the pyroptosis-related proteins GSDMD, NLRP3, cleaved caspase-1, and mature IL-1β, which were elevated in mice with nephrolithiasis, and repressed apoptosis and the expression of OPN and CD44. Moreover, vitexin mitigated F4/80-positive macrophage infiltration and MCP-1 expression in the kidneys. Furthermore, an in vitro study showed that vitexin increased the viability of HK-2 cells and THP-1-derived macrophages, which was impaired by treatment with COM crystals, decreased the medium lactate dehydrogenase (LDH) level, and inhibited the expression of pyroptosis-related proteins in HK-2 cells and macrophages. Vitexin repressed EMT of HK-2 cells, with increased expression of pan-cytokeratin (Pan-ck) and decreased expression of Vimentin and alpha-smooth muscle actin (α-SMA), and downregulated the Wnt/β-catenin pathway. Moreover, vitexin suppressed tumor necrosis factor-α (TNF-α) and IL-1β mRNA expression, which was upregulated by COM in macrophages.

Conclusion: Vitexin exerts protective effects against nephrolithiasis by inhibiting pyroptosis activation, apoptosis, EMT, and macrophage infiltration. In addition, GSDMD-related pyroptosis mediates nephrolithiasis.
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http://dx.doi.org/10.1016/j.phymed.2021.153562DOI Listing
June 2021

Overexpression of SlGATA17 Promotes Drought Tolerance in Transgenic Tomato Plants by Enhancing Activation of the Phenylpropanoid Biosynthetic Pathway.

Front Plant Sci 2021 16;12:634888. Epub 2021 Mar 16.

Laboratory of Genetic Breeding in Tomato, College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, China.

GATA transcription factors (TFs) are widely distributed in eukaryotes. Some GATA TFs have been shown to be related to photosynthesis, germination, circadian rhythm, and other functions in plants. Our previous study found that some members of this family have obvious responses when tomato plants are subjected to drought stress, in which the gene is significantly upregulated. To further verify the function of this gene under drought stress, we constructed tomato lines with this gene overexpressed. Phenotypic and physiological indicators indicated that the overexpressing plants were more drought tolerant than the wild-type plants. Transcriptomic sequencing results showed that the overexpression of the gene improved the activity of the phenylpropanoid biosynthesis pathway. The PAL enzyme activity assay results confirmed that the initial activity of this pathway was enhanced in transgenic plants, especially in the initial response stage, indicating that the gene regulates the drought resistance of tomato plants by regulating the activity of the phenylpropanoid biosynthesis pathway.
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http://dx.doi.org/10.3389/fpls.2021.634888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008128PMC
March 2021

Weight-bearing exercise prevents skeletal muscle atrophy in ovariectomized rats.

J Physiol Biochem 2021 Mar 31. Epub 2021 Mar 31.

Department of Electronic Engineering, Fudan University, Shanghai, 200433, China.

Skeletal muscle atrophy (SMA) is a dominant symptom induced by estrogen deficiency which can lead to severe health problems of postmenopausal women. Furthermore, estrogen deficiency has severely compromised the maintenance of muscle stem cells as well as impairs self-renewal and differentiation into muscle fibers. Resistance training is commonly considered as a positive and useful intervention in accelerating the rate of muscle growth. As one of the resistance training, whether the weight-bearing exercise can alleviate SMA induced by estrogen deficiency has not been investigated. The rats were divided into 3 groups randomly: sham group, ovariectomized (OVX) group, and weight-bearing exercise (WBE) therapeutic group. The weight that rats were loaded was 35% of their body weight, and the rats were trained by treadmill training (5° slope, 20 m/min, 30 min/day, 6 days/week) for 8 weeks. After training, the quality and strength of skeletal muscle of the WBE rats were improved; meanwhile, the cross-sectional areas of the skeletal muscle were also increased. Moreover, the WBE activated Akt significantly, upregulated the expression of mTOR, and downregulated the expression of MSTN and its receptor ActRIIB and FoxO1, respectively. The SMA phenomena of rats which induced by estrogen deficiency were prevented effectively via WBE, and the MSTN/Akt/mTOR and FoxO1 signaling pathway may be the predominant way in this improvement.
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http://dx.doi.org/10.1007/s13105-021-00794-0DOI Listing
March 2021

Characteristics of Online Health Care Services From China's Largest Online Medical Platform: Cross-sectional Survey Study.

J Med Internet Res 2021 04 15;23(4):e25817. Epub 2021 Apr 15.

Ping An Healthcare Technology, Beijing, China.

Background: Internet hospitals in China are in great demand due to limited and unevenly distributed health care resources, lack of family doctors, increased burdens of chronic diseases, and rapid growth of the aged population. The COVID-19 epidemic catalyzed the expansion of online health care services. In recent years, internet hospitals have been rapidly developed. Ping An Good Doctor is the largest, national online medical entry point in China and is a widely used platform providing online health care services.

Objective: This study aims to give a comprehensive description of the characteristics of the online consultations and inquisitions in Ping An Good Doctor. The analyses tried to answer the following questions: (1) What are the characteristics of the consultations in Ping An Good Doctor in terms of department and disease profiles? (2) Who uses the online health services most frequently? and (3) How is the user experience of the online consultations of Ping An Good Doctor?

Methods: A total of 35.3 million consultations and inquisitions over the course of 1 year were analyzed with respect to the distributions of departments and diseases, user profiles, and consulting behaviors.

Results: The geographical distribution of the usage of Ping An Good Doctor showed that Shandong (18.4%), Yunnan (15.6%), Shaanxi (7.2%), and Guangdong (5.5%) were the provinces that used it the most; they accounted for 46.6% of the total consultations and inquisitions. In terms of department distribution, we found that gynecology and obstetrics (19.2%), dermatology (17.0%), and pediatrics (14.4%) were the top three departments in Ping An Good Doctor. The disease distribution analysis showed that, except for nondisease-specific consultations, acute upper respiratory infection (AURI) (4.1%), pregnancy (2.8%), and dermatitis (2.4%) were the most frequently consulted diseases. In terms of user profiles, females (60.4%) from 19 to 35 years of age were most likely to seek consultations online, in general. The user behavior analyses showed that the peak times of day for online consultations occurred at 10 AM, 3 PM, and 9 PM. Regarding user experience, 93.0% of users gave full marks following their consultations. For some disease-related health problems, such as AURI, dermatitis, and eczema, the feedback scores were above average.

Conclusions: The prevalence of internet hospitals, such as Ping An Good Doctor, illustrated the great demand for online health care services that can go beyond geographical limitations. Our analyses showed that nondisease-specific issues and moderate health problems were much more frequently consulted about than severe clinical conditions. This indicated that internet hospitals played the role of the family doctor, which helped to relieve the stress placed on offline hospitals and facilitated people's lives. In addition, good user experiences, especially regarding disease-related inquisitions, suggested that online health services can help solve health problems. With support from the government and acceptance by the public, online health care services could develop at a fast pace and greatly benefit people's daily lives.
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http://dx.doi.org/10.2196/25817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051434PMC
April 2021

Multiplex indexing approach for the detection of DNase I hypersensitive sites in single cells.

Nucleic Acids Res 2021 Mar 8. Epub 2021 Mar 8.

Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.

Single cell chromatin accessibility assays reveal epigenomic variability at cis-regulatory elements among individual cells. We previously developed a single-cell DNase-seq assay (scDNase-seq) to profile accessible chromatin in a limited number of single cells. Here, we report a novel indexing strategy to resolve single-cell DNase hypersensitivity profiles based on bulk cell analysis. This new technique, termed indexing single-cell DNase sequencing (iscDNase-seq), employs the activities of terminal DNA transferase (TdT) and T4 DNA ligase to add unique cell barcodes to DNase-digested chromatin ends. By a three-layer indexing strategy, it allows profiling genome-wide DHSs for >15 000 single-cells in a single experiment. Application of iscDNase-seq to human white blood cells accurately revealed specific cell types and inferred regulatory transcription factors (TF) specific to each cell type. We found that iscDNase-seq detected DHSs with specific properties related to gene expression and conservation missed by scATAC-seq for the same cell type. Also, we found that the cell-to-cell variation in accessibility computed using iscDNase-seq data is significantly correlated with the cell-to-cell variation in gene expression. Importantly, this correlation is significantly higher than that between scATAC-seq and scRNA-seq, suggesting that iscDNase-seq data can better predict the cellular heterogeneity in gene expression compared to scATAC-seq. Thus, iscDNase-seq is an attractive alternative method for single-cell epigenomics studies.
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http://dx.doi.org/10.1093/nar/gkab102DOI Listing
March 2021

A Bioadhesive Barrier-Forming Oral Liquid Gel Improved Oral Mucositis and Nutritional Status in Patients With Head and Neck Cancers Undergoing Radiotherapy: A Retrospective Single Center Study.

Front Oncol 2021 22;11:617392. Epub 2021 Feb 22.

Department of Radiation Oncology, The First Hospital, Jilin University, Changchun, China.

Background: Episil is a bioadhesive barrier-forming oral liquid gel that can relieve oral mucositis (OM) caused by radiotherapy (RT) and hence relieves pain effectively. In this study, we observed the effects of Episil on the OM and nutritional status of patients with head and neck cancers (HNCs) undergoing RT.

Methods: A total of 50 HNC patients were divided into the Episil (25 patients) and control (25 patients) groups. Patients in the Episil group were sprayed with Episil. In the control group, the kangfuxin solution or Kangsu™ oral gargle was used. Medical staff assessed the OM extent and timing as well as the nutritional status during treatment and recorded adverse reactions other than OM. The nutritional status assessment included the following indicators: Patient Generated-Subjective Global Assessment (PG-SGA) score, body mass index (BMI), body weight, albumin levels, and other hematological indicators.

Results: The incidence of high-level OM (III-IV) after RT was lower in the Episil group than in the control group ( < 0.05). Nutritional status assessments showed that the Episil group had a lower percentage of weight loss than the control group at weeks 4 and 7 after RT. Similar results were also obtained for BMI and albumin levels ( < 0.05). Moreover, according to PG-SGA scores, fewer patients in the Episil group were malnourished and more patients were well-nourished ( < 0.05) compared with the control group.

Conclusion: Episil effectively improved OM and malnutrition in HNC patients who received RT and has a good clinical application value.
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http://dx.doi.org/10.3389/fonc.2021.617392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937867PMC
February 2021

Biphasic activation of survival and death pathways in Arabidopsis thaliana cultured cells by sorbitol-induced hyperosmotic stress.

Plant Sci 2021 Apr 9;305:110844. Epub 2021 Feb 9.

Université de Paris, Laboratoire des Energies de Demain, Paris, France; former EA3514, Université Paris Diderot, Paris, France; LINV-DiSPAA, Department of Agri-Food and Environmental Science, University of Florence, Viale delle Idee 30, 50019, Sesto Fiorentino (FI), Italy; University of Florence LINV Kitakyushu Research Center (LINV@Kitakyushu), Kitakyushu, Japan. Electronic address:

Hyperosmotic stresses represent some of the most serious abiotic factors that adversely affect plants growth, development and fitness. Despite their central role, the early cellular events that lead to plant adaptive responses remain largely unknown. In this study, using Arabidopsis thaliana cultured cells we analyzed early cellular responses to sorbitol-induced hyperosmotic stress. We observed biphasic and dual responses of A. thaliana cultured cells to sorbitol-induced hyperosmotic stress. A first set of events, namely singlet oxygen (O) production and cell hyperpolarization due to a decrease in anion channel activity could participate to signaling and osmotic adjustment allowing cell adaptation and survival. A second set of events, namely superoxide anion (O) production by RBOHD-NADPH-oxidases and SLAC1 anion channel activation could participate in programmed cell death (PCD) of a part of the cell population. This set of events raises the question of how a survival pathway and a death pathway could be induced by the same hyperosmotic condition and what could be the meaning of the induction of two different behaviors in response to hyperosmotic stress.
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http://dx.doi.org/10.1016/j.plantsci.2021.110844DOI Listing
April 2021

Mesoscale Modelling of Concretes Subjected to Triaxial Loadings: Mechanical Properties and Fracture Behaviour.

Materials (Basel) 2021 Feb 26;14(5). Epub 2021 Feb 26.

Institute of Applied Mechanics, College of Mechanical and Vehicle Engineering, Taiyuan University of Technology, Taiyuan 030024, China.

The mechanical properties and fracture behaviour of concretes under different triaxial stress states were investigated based on a 3D mesoscale model. The quasistatic triaxial loadings, namely, compression-compression-compression (C-C-C), compression-tension-tension (C-T-T) and compression-compression-tension (C-C-T), were simulated using an implicit solver. The mesoscopic modelling with good robustness gave reliable and detailed damage evolution processes under different triaxial stress states. The lateral tensile stress significantly influenced the multiaxial mechanical behaviour of the concretes, accelerating the concrete failure. With low lateral pressures or tensile stress, axial cleavage was the main failure mode of the specimens. Furthermore, the concretes presented shear failures under medium lateral pressures. The concretes experienced a transition from brittle fracture to plastic failure under high lateral pressures. The Ottosen parameters were modified by the gradient descent method and then the failure criterion of the concretes in the principal stress space was given. The failure criterion could describe the strength characteristics of concrete materials well by being fitted with experimental data under different triaxial stress states.
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http://dx.doi.org/10.3390/ma14051099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956416PMC
February 2021

Using Network Pharmacology to Explore the Mechanism of Peach Kernel-Safflower in the Treatment of Diabetic Nephropathy.

Biomed Res Int 2021 1;2021:6642584. Epub 2021 Feb 1.

Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.

Objective: The mechanism of peach kernel-safflower in treating diabetic nephropathy (DN) was investigated using network pharmacology.

Methods: Network pharmacology methodology was applied to screen the effective compounds of peach kernel-safflower in the SymMap and TCMSP databases. Potential targets were then screened in the ETCM, SEA, and SymMap databases to construct a compound-target network. This was followed by screening of DN targets in OMIM, Gene, and GeneCards databases. The common targets of drugs and diseases were selected for analysis in the STRING database, and the results were imported into Cytoscape 3.8.0 to construct a protein-protein interaction network. Next, GO and KEGG enrichment analyses were performed. Finally, Schrödinger molecular docking verified the reliability of the results.

Results: A total of 23 effective compounds and 794 potential targets resulted from our screening process. Quercetin and luteolin were identified as the main effective ingredients in peach kernel-safflower. Furthermore, five key targets (VEGFA, IL6, TNF, AKT1, and TP53), AGE-RAGE, fluid shear stress and atherosclerosis, IL-17, and HIF-1 signaling pathways may be involved in the treatment of DN using peach kernel-safflower.

Conclusions: This study embodies the complex network relationship of multicomponents, multitargets, and multipathways of peach kernel-safflower to treat DN and provides a basis for further research on its mechanism.
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http://dx.doi.org/10.1155/2021/6642584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870307PMC
February 2021

Tangshen Formula Attenuates Diabetic Kidney Injury by Imparting Anti-pyroptotic Effects the TXNIP-NLRP3-GSDMD Axis.

Front Pharmacol 2020 29;11:623489. Epub 2021 Jan 29.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

We previously reported that Tangshen formula (TSF), a Chinese herbal medicine for diabetic kidney disease (DKD) therapy, imparts renal protective effects. However, the underlying mechanisms of these effects remain unclear. Pyroptosis is a form of programmed cell death that can be triggered by the NLRP3 inflammasome. Recently, the association between the pyroptosis of renal resident cells and DKD was established, but with limited evidence. This study aimed to investigate whether the renal protective effects of TSF are related to its anti-pyroptotic effect. DKD rats established by right uninephrectomy plus a single intraperitoneal injection of STZ and HK-2 cells stimulated by AGEs were used. , TSF reduced the 24 h urine protein (24 h UP) of DKD rats and alleviated renal pathological changes. Meanwhile, the increased expression of pyroptotic executor (GSDMD) and NLRP3 inflammasome pathway molecules (NLRP3, caspase-1, and IL-1β) located in the tubules of DKD rats were downregulated with TSF treatment. , we confirmed the existence of pyroptosis in AGE-stimulated HK-2 cells and the activation of the NLRP3 inflammasome. TSF reduced pyroptosis and NLRP3 inflammasome activation in a dosage-dependent manner. Then, we used nigericin to determine that TSF imparts anti-pyroptotic effects by inhibiting the NLRP3 inflammasome. Finally, we found that TSF reduces reactive oxygen species (ROS) production and thioredoxin-interacting protein (TXNIP) expression in AGE-stimulated HK-2 cells. More importantly, TSF decreased the colocalization of TXNIP and NLRP3, indicating that ROS-TXNIP may be the target of TSF. In summary, the anti-pyroptotic effect the TXNIP-NLRP3-GSDMD axis may be an important mechanism of TSF for DKD therapy.
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http://dx.doi.org/10.3389/fphar.2020.623489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880163PMC
January 2021

High-resolution mapping of reproductive tract infections among women of childbearing age in Bangladesh: a spatial-temporal analysis of the demographic and health survey.

BMC Public Health 2021 Feb 12;21(1):342. Epub 2021 Feb 12.

Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China.

Background: Reproductive tract infections (RTIs) have become major but silent public health problems devastating women's lives in Bangladesh. Accurately and precisely identifying high-risk areas of RTIs through high-resolution risk maps is meaningful for resource-limited settings.

Methods: We obtained data reported with RTI symptoms by women of childbearing age in the years 2007, 2011 and 2014 from Bangladesh Demographic and Health Survey. High-spatial Environmental, socio-economic and demographic layers were downloaded from different open-access data sources. We applied Bayesian spatial-temporal models to identify important influencing factors and to estimate the infection risk at 5 km spatial resolution across survey years in Bangladesh.

Results: We estimated that in Bangladesh, there were approximate 11.1% (95% Bayesian credible interval, BCI: 10.5-11.7%), 13.9% (95% BCI: 13.3-14.5%) and 13.4% (95% BCI: 12.8-14.0%) of women of childbearing age reported with RTI symptoms in 2007, 2011 and 2014, respectively. The risk of most areas shows an obvious increase from 2007 to 2011, then became stable between 2011 and 2014. High risk areas were identified in the southern coastal areas, the western Rajshahi Division, the middle of Khulna Division, and the southwestern Chittagong Division in 2014. The prevalence of Rajshahi and Nawabganj District were increasing during all the survey years.

Conclusion: The high-resolution risk maps of RTIs we produced can guide the control strategies targeted to priority areas cost-effectively. More than one eighth of women of childbearing age reported symptoms suggesting RTIs and the risk of RTIs varies in different geographical area, urging the government to pay more attention to the worrying situation of female RTIs in the country.
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http://dx.doi.org/10.1186/s12889-021-10360-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881647PMC
February 2021

Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2.

Curr Drug Metab 2021 Feb 9. Epub 2021 Feb 9.

College of Pharmacy, Dalian Medical University, Dalian, 116044. China.

Background: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear.

Objective: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism.

Methods: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2.

Results: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 μM, 8.63 μM and 29.0 μM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2.

Conclusion: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.
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http://dx.doi.org/10.2174/1389200222666210210115509DOI Listing
February 2021

Longitudinal effects of low-intensity pulsed ultrasound on osteoporosis and osteoporotic bone defect in ovariectomized rats.

Ultrasonics 2021 May 23;113:106360. Epub 2021 Jan 23.

Department of Electronic Engineering, Fudan University, Shanghai 200433, China; Academy for Engineering and Technology, Fudan University, Shanghai 200433, China. Electronic address:

Low-intensity pulsed ultrasound (LIPUS) with an intensity (spatial average temporal average, I) of 30 mW/cm has been widely proved to be effective on impaired bone healing, but showing little effectiveness in the treatment of osteoporosis. We hypothesized that the intensity of LIPUS may be a key factor in explaining this difference, thus two intensity levels, the widely used 30 mW/cm and a higher 150 mW/cm, were used to simultaneously treat osteoporosis and osteoporotic bone defect in ovariectomized (OVX) rats with a 1-mm drill hole on their left femurs.Results showed that 150 mW/cm LIPUS augmented the healing rate of the drill hole than 30 mW/cm after 3-week LIPUS treatment, although did not further enhance the healing rate after 6-week LIPUS treatment. For ameliorating osteoporosis, 150 mW/cm LIPUS achieved more advantages over 30 mW/cm in improving bone density, microstructure and biomechanics 6 weeks after LIPUS intervention. In conclusion, LIPUS with an intensity of 30 mW/cm was sufficient to facilitate bone defect healing, but a higher intensity can be considered as a rapid trigger for osteoporotic bone repair. In addition, improving the intensity of LIPUS may be a potentially effective consideration for alleviation of osteoporosis, and the LIPUS regimen in the treatment of osteoporosis remains to be optimized.
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http://dx.doi.org/10.1016/j.ultras.2021.106360DOI Listing
May 2021

Positive Effects of Kangaroo Mother Care on Long-Term Breastfeeding Rates, Growth, and Neurodevelopment in Preterm Infants.

Breastfeed Med 2021 Apr 2;16(4):282-291. Epub 2021 Feb 2.

School of Nursing, University of Connecticut, Storrs, Connecticut, USA.

Kangaroo mother care (KMC) benefits preterm infants' health through increasing breastfeeding, but the longitudinal effects of KMC remain unknown. This study investigates the impact of KMC on breastfeeding and health outcomes in Chinese preterm infants. A longitudinal randomized controlled study was conducted with 79 preterm infant-mother dyads. The KMC group ( = 36) was provided 2.5 hours/day KMC during the neonatal intensive care unit (NICU) hospitalization, while the control group ( = 43) received standard care. Infant's feeding regimens and physical growth were documented daily at NICU. Physical growth and Neonatal Behavioral Neurological Assessment were measured at 40 weeks, 3 months, and 6 months of corrected age (CA). Breastfeeding outcomes were documented at 6 months of CA. Compared with the control group, KMC infants received higher mothers' milk proportion during hospitalization ( = 0.16, confidence interval [CI] = [0.11-0.21]) and less feeding intolerance at discharge (odds ratio [OR] = 0.11, CI = [0.02-0.43]); and higher exclusive breastfeeding proportion (OR = 14.6, CI = [3.5-60.9]) at 6 months CA. KMC infants also had significant increased body weight and body length at hospital discharge; and more increases of body weight, body length, and head circumference in follow-ups. The neurobehavioral score was also higher in the KMC group compared to the control group over time. Longitudinal KMC effects are significant in promoting preterm infants' breastfeeding outcomes, growth, and neurodevelopment. Early initiation of KMC practice is highly recommended to the parent-infant population in Chinese NICUs to promote breastfeeding and developmental outcomes.
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http://dx.doi.org/10.1089/bfm.2020.0358DOI Listing
April 2021

Genome-wide identification and functional analysis of the ERF2 gene family in response to disease resistance against Stemphylium lycopersici in tomato.

BMC Plant Biol 2021 Feb 2;21(1):72. Epub 2021 Feb 2.

Laboratory of Genetic Breeding in Tomato, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Affairs, College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, 150030, China.

Background: APETALA2/ethylene responsive factor (AP2/ERF) transcription factors are a plant-specific family of transcription factors and one of the largest families of transcription factors. Ethylene response factors (ERF) regulate plant growth, development, and responses to biotic and abiotic stress. In a previous study, the ERF2 gene was significantly upregulated in both resistant and susceptible tomato cultivars in response to Stemphylium lycopersici. The main purpose of this study was to systematically analyze the ERF family and to explore the mechanism of ERF2 in tomato plants resisting pathogen infection by the Virus-induced Gene Silencing technique.

Results: In this experiment, 134 ERF genes were explored and subjected to bioinformatic analysis and divided into twelve groups. The spatiotemporal expression characteristics of ERF transcription factor gene family in tomato were diverse. Combined with RNA-seq, we found that the expression of 18 ERF transcription factors increased after inoculation with S. lycopersici. In ERF2-silenced plants, the susceptible phenotype was observed after inoculation with S. lycopersici. The hypersensitive response and ROS production were decreased in the ERF2-silenced plants. Physiological analyses showed that the superoxide dismutase, peroxidase and catalase activities were lower in ERF2-silenced plants than in control plants, and the SA and JA contents were lower in ERF2-silenced plants than in control plants after inoculation with S. lycopersici. Furthermore, the results indicated that ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance.

Conclusions: In this study, we identified and analyzed members of the tomato ERF family by bioinformatics methods and classified, described and analyzed these genes. Subsequently, we used VIGS technology to significantly reduce the expression of ERF2 in tomatoes. The results showed that ERF2 had a positive effect on tomato resistance to S. lycopersici. Interestingly, ERF2 played a key role in multiple SA, JA and ROS signaling pathways to confer resistance to invasion by S. lycopersici. In addition, ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance to S. lycopersici. In summary, this study provides gene resources for breeding for disease resistance in tomato.
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http://dx.doi.org/10.1186/s12870-021-02848-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856819PMC
February 2021

Mapping spatial and temporal variation of seafloor organic matter ΔC and δC in the Northern Gulf of Mexico following the Deepwater Horizon Oil Spill.

Mar Pollut Bull 2021 Mar 30;164:112076. Epub 2021 Jan 30.

Department of Earth, Ocean and Atmospheric Science, Florida State University, 1011 Academic Way, Tallahassee, FL 32306-4350, United States. Electronic address:

Following the Deepwater Horizon oil spill of 2010, large amounts of biodegraded oil (petrocarbon) sank to the seafloor. Our objectives were to 1) determine post-spill isotopic values as the sediments approached a new baseline and 2) track the recovery of affected sediments. Sediment organic carbon δC and ΔC reached a post-spill baseline averaging -21.2 ± 0.9‰ (n = 129) and -220 ± 66‰ (n = 95). Spatial variations in seafloor organic carbon baseline isotopic values, C and C, were influenced by river discharge and hydrocarbon seepage, respectively. Inverse Distance Weighting of surface sediment ΔC values away from seep sites showed a 50% decrease in the total mass of petrocarbon, from 2010 to 2014. We estimated a rate of loss of -2 × 10 g of petrocarbon-C/year, 2-11% of the degradation rates in surface slicks. Despite the observed recovery in sediments, lingering residual material in the surface sediments was evident seven years following the blowout.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112076DOI Listing
March 2021

Catalpol-Induced AMPK Activation Alleviates Cisplatin-Induced Nephrotoxicity through the Mitochondrial-Dependent Pathway without Compromising Its Anticancer Properties.

Oxid Med Cell Longev 2021 15;2021:7467156. Epub 2021 Jan 15.

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.

Nephrotoxicity is a common complication of cisplatin chemotherapy and, thus, limits the clinical application of cisplatin. In this work, the effects of catalpol (CAT), a bioactive ingredient extracted from Rehmannia glutinosa, on cisplatin-induced nephrotoxicity and antitumor efficacy were comprehensively investigated. Specifically, the protective effect of CAT on cisplatin-induced injury was explored in mice and HK-2 cells. , CAT administration strikingly suppressed cisplatin-induced renal dysfunction, morphology damage, apoptosis, and inflammation. , CAT induced activation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), improved mitochondrial function, and decreased generation of cellular reactive oxygen species (ROS), leading to a reduction in inflammation and apoptosis, which ultimately protected from cisplatin-induced injury. However, the beneficial effects of CAT were mostly blocked by coincubation with compound C. Furthermore, molecular docking results indicated that CAT had a higher affinity for AMPK than other AMPK activators such as danthron, phenformin, and metformin. Importantly, CAT possessed the ability to reverse drug resistance without compromising the antitumor properties of cisplatin. These findings suggest that CAT exerts positive effects against cisplatin-induced renal injury through reversing drug resistance via the mitochondrial-dependent pathway without affecting the anticancer activity of cisplatin.
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http://dx.doi.org/10.1155/2021/7467156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826214PMC
January 2021

Association between LXR- and ABCA1 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus in a Chinese Han Population.

J Diabetes Res 2020 22;2020:8721536. Epub 2020 Dec 22.

Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, China.

We designed a case-control study and selected rs7120118 C>T and rs2230806 A>G polymorphisms to determine the correlation between these polymorphisms and diabetic kidney disease (DKD) susceptibility in a Chinese Han population. Three hundred DKD patients and 346 type 2 diabetes mellitus (DM) patients without kidney disease were recruited. Our results showed that rs7120118 was associated with DKD (genotype, = .027; allele, < .011). rs7120118 was associated with a higher risk of DKD under a dominant model adjustment by age and sex ( = .015) and an additive model ( = .040); rs2230806 was associated with a higher risk of DKD under an recessive model ( < .03); the combined effect of rs7120118 CC+rs2230806 GG genotype showed an association of DKD adjustment for age and sex ( = .009). In subgroup analysis of patients without hypercholesterolemia, the rs2230806 genotype frequencies were different between the two groups ( = .042). rs2230806 was associated with increased risk of DKD under a recessive model adjustment for age and sex ( = .013) and an additive model ( = .031). Our results suggest that rs7120118 is significantly associated with a higher risk of DKD, and rs2230806 is significantly associated with a higher risk of DKD without hypercholesterolemia in Chinese Han individuals.
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http://dx.doi.org/10.1155/2020/8721536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772016PMC
December 2020

Inhibitory Effects of Genistein on Vascular Smooth Muscle Cell Proliferation Induced by Ox-LDL: Role of BKCa Channels.

Anal Cell Pathol (Amst) 2020 13;2020:8895449. Epub 2020 Dec 13.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001 Heilongjiang Province, China.

Background: Oxidized low-density lipoprotein (Ox-LDL) is a crucial pathogenic factor for vascular diseases, which can induce the proliferation of vascular smooth muscle cells (VSMCs). Genistein is the main component of soybean isoflavone. Genistein has a variety of pharmacological properties in the treatment of vascular diseases and a promising clinical application. Large-conductance calcium-activated potassium (BKCa) channels are the primary type of potassium channels in VSMCs, which regulate various biological functions of VSMCs. However, whether genistein exerts an antiproliferation effect on Ox-LDL-stimulated VSMCs remains unclear. The current study is aimed at elucidating the effect of genistein on the Ox-LDL-stimulated proliferation of VSMCs and its possible molecular mechanism, especially the electrophysiological mechanism related to BKCa channels.

Methods: Monoculture VSMC was obtained by an acute enzyme-dispersing method. The proliferation of cells was measured by CCK-8, cell cycle, and proliferating cell nuclear antigen (PCNA) expression. The BKCa whole-cell currents were measured by patch-clamp.

Results: Ox-LDL treatment induced the proliferation of VSMCs, upregulated the BKCa protein expression, and increased the density of BKCa currents, while genistein significantly inhibited these effects caused by Ox-LDL. BKCa channels exerted a regulatory role in the proliferation of VSMCs in response to Ox-LDL. The inhibition of BKCa channels suppressed Ox-LDL-stimulated VSMC proliferation, while the activation of BKCa channels showed the opposite effect. Moreover, genistein suppressed the activity of BKCa, including protein expression and current density in a protein tyrosine kinase- (PTK-) dependent manner.

Conclusion: This study demonstrated that genistein inhibited the Ox-LDL-mediated proliferation of VSMCs by blocking the cell cycle progression; the possible molecular mechanism may be related to PTK-dependent suppression of BKCa channels. Our results provided novel ideas for the application of genistein in the treatment of vascular diseases and proposed a unique insight into the antiproliferative molecular mechanism of genistein.
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http://dx.doi.org/10.1155/2020/8895449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752275PMC
December 2020

Identifying the Dominant Contribution of Human Cytochrome P450 2J2 to the Metabolism of Rivaroxaban, an Oral Anticoagulant.

Cardiovasc Drugs Ther 2021 Jan 7. Epub 2021 Jan 7.

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, 116044, China.

Purpose: Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety.

Methods: The metabolic stability of rivaroxaban in the presence of human liver microsomes (HLMs) and recombinant CYPs was systematically evaluated to estimate the participation of various CYP isoforms. Furthermore, the catalytic efficiency of CYP isoforms was compared via metabolic kinetic studies of rivaroxaban with recombinant CYP isoenzymes, as well as via CYP-specific inhibitory studies. Additionally, docking simulations were used to illustrate molecular interactions.

Results: Multiple CYP isoforms were involved in the hydroxylation of rivaroxaban, with decreasing catalytic rates as follows: CYP2J2 > 3A4 > 2D6 > 4F3 > 1A1 > 3A5 > 3A7 > 2A6 > 2E1 > 2C9 > 2C19. Among the CYPs, 2J2, 3A4, 2D6, and 4F3 were the four major isoforms responsible for rivaroxaban metabolism. Notably, the intrinsic clearance of rivaroxaban catalyzed by CYP2J2 was nearly 39-, 64-, and 100-fold that catalyzed by CYP3A4, 2D6, and 4F3, respectively. In addition, rivaroxaban hydroxylation was inhibited by 41.1% in the presence of the CYP2J2-specific inhibitor danazol, which was comparable to the inhibition rate of 43.3% by the CYP3A-specific inhibitor ketoconazole in mixed HLMs. Furthermore, molecular simulations showed that rivaroxaban is principally bound to CYP2J2 by π-alkyl bonds, carbon-hydrogen bonds, and alkyl interactions.

Conclusion: CYP2J2 dominated the hydroxylation of rivaroxaban, which may provide new insight into clinical drug interactions involving rivaroxaban.
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http://dx.doi.org/10.1007/s10557-020-07129-zDOI Listing
January 2021

More Symmetrical "Hot Spots" Ensure Stronger Plasmon-Enhanced Fluorescence: From Au Nanorods to Nanostars.

Anal Chem 2021 02 7;93(4):2480-2489. Epub 2021 Jan 7.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.

Plasmon-enhanced fluorescence (PEF) is considered to be a powerful signal amplification technology to overcome intrinsic shortcomings of photobleaching and brightness of the traditional fluorescent dyes. Nevertheless, exploitation of PEF-based probes for bioimaging application is still at a very early stage. In this work, a simple but powerful gold nanostar (Au NST)@SiO-based PEF probe with 20 symmetric "hot spots" was developed for highly sensitive "lighting up" in situ imaging of intracellular microRNAs (miRNAs). By regulating the thickness of the silica shell, the distance between Au NSTs and fluorescent dyes was controlled, and the optimum fluorescence enhancement (21-fold) was obtained with the silica shell thickness of approximately 22 nm. Thanks to the 20 more powerful "hot spots" that can produce stronger localized electric fields, the Au NST-based PEF probe exhibits stronger PEF effects than the traditional plasmonic nanostructures such as gold nanorods (Au NRs), gold nanobipyramids (Au NBPs), and triangular gold nanoprisms (Au NPRs), resulting in high sensitivity and improved detection limit (LOD) of 0.21 pM for miRNA-21 analysis. Moreover, not only cancer cells (MCF-7 and Hela) and normal cells (L02) with distinct miRNA-21 expression levels can be discriminated but also tumor cells in co-cultured mixtures can be recognized, indicating its promising potential in clinical diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.0c04518DOI Listing
February 2021

Genomic variants in Fas-mediated apoptosis pathway predict a poor response to Platinum-based Chemotherapy for Chinese Gastric Cancer Patients.

J Cancer 2021 1;12(3):849-859. Epub 2021 Jan 1.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 21000, China.

Platinum-based adjuvant chemotherapy is very common for gastric cancer (GC) patients, but the chemotherapy sensitivity is very heterogeneous. The genomic variants and the gene-gene interactions involved in Fas-mediated apoptosis pathway including Fas (FAS 1377 G > A and 670 A > G), FasL (FASL 844 C > T) and caspase-8 (CASP8 -652 6N ins > del or I > D), may paly vital roles in the response to platinum-based treatment. In our investigation, 662 stage II-III postoperative GC patients were enrolled between 1998 and 2006. 261 patients accepted platinum-based regimens and the remaining 401 were not. The log rank tests, Kaplan Meier plots, Pearson chi-square tests, Student t-tests and Cox regression analyses were performed. For the chemotherapy cohort, FAS 1377 G > A or FAS 670 A > G variants alone was related with inferior survival, and a greater than additive effect was identified when patients simultaneously carrying FAS 1377 GA and FAS 670 GA genotypes. But the poor response was neutralized when patients simultaneously carrying FASL 844 C > T or CASP8 -652 6N ins > del mutations. Our study suggested that FAS 1377 G > A and FAS 670 A > G variants may serve as potential biomarkers to predict the response to platinum-based adjuvant chemotherapy, and the gene-gene interactions involved in Fas-mediated apoptosis pathway may enhance or neutralize the chemosensitivity.
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http://dx.doi.org/10.7150/jca.48120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778532PMC
January 2021

The non-negligibility of greenhouse gas emission from a combined pre-composting and vermicomposting system with maize stover and cow dung.

Environ Sci Pollut Res Int 2021 Apr 4;28(15):19412-19423. Epub 2021 Jan 4.

College of Biological and Agricultural Engineering, Jilin University, Changchun, 130022, China.

The acceptance of combined pre-composting and vermicomposting systems is increasing because of the advantage in rapidly stabilizing organic wastes and reducing emission of greenhouse gasses (GHG). However, GHG emission during the pre-composting phase is often neglected when evaluating the system. This study aimed to quantify GHG emission from a combined pre-composting and vermicomposting system and to investigate the effects of earthworms on GHG emission. A combined system using Eisenia fetida was employed to stabilize maize stover and cow dung (mixing ratio 60:40). The inoculating densities were 60 (T), 120 (T), and 180 (T) earthworms per kilogram of substrate. A traditional composting system without earthworms was set as a control (T). The results indicated that earthworms increased CO while decreased CH and NO emissions compared to the control. Higher emission of CO suggested that the earthworms promoted the degradation of the substrates. Lower emission of CH and NO showed the advantage of the combined system because CH and NO possess extremely higher global warming potential than that of CO. T is recommended for stabilizing maize stover and cow dung when making a tradeoff between stabilization rate and reduction of GHG. The percentages of GHG emission during pre-composting relative to total GHG emission in T, T, and T were 34%, 35%, and 30%, respectively. GHG emission is non-negligible when using a combined system, especially the emission of GHG during the pre-composting phase cannot be ignored.
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http://dx.doi.org/10.1007/s11356-020-12172-2DOI Listing
April 2021

Deep-gKnock: Nonlinear group-feature selection with deep neural networks.

Neural Netw 2021 Mar 14;135:139-147. Epub 2020 Dec 14.

Department of Electrical and Computer Engineering, Northeastern University, United States of America.

Feature selection is central to contemporary high-dimensional data analysis. Group structure among features arises naturally in various scientific problems. Many methods have been proposed to incorporate the group structure information into feature selection. However, these methods are normally restricted to a linear regression setting. To relax the linear constraint, we design a new Deep Neural Network (DNN) architecture and integrating it with the recently proposed knockoff technique to perform nonlinear group-feature selection with controlled group-wise False Discovery Rate (gFDR). Experimental results on high-dimensional synthetic data demonstrate that our method achieves the highest power and accurate gFDR control compared with state-of-the-art methods. The performance of Deep-gKnock is especially superior in the following five situations: (1) nonlinearity relationship; (2) dimension p greater than sample size n; (3) high between-group correlation; (4) high within-group correlation; (5) large number of associated groups. And Deep-gKnock is also demonstrated to be robust to the misspecification of the feature distribution and the change of network architecture. Moreover, Deep-gKnock achieves scientifically meaningful group-feature selection results for cutting-edge real world datasets.
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http://dx.doi.org/10.1016/j.neunet.2020.12.004DOI Listing
March 2021

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia.

Cochrane Database Syst Rev 2020 12 24;12:CD008367. Epub 2020 Dec 24.

Hubei-MOST KLOS & KLOBM, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Background: Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in people who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, swab, toothbrush, or combination, together with suction of secretions, may reduce the risk of VAP in these patients.

Objectives: To assess the effects of oral hygiene care (OHC) on incidence of ventilator-associated pneumonia in critically ill patients receiving mechanical ventilation in hospital intensive care units (ICUs).

Search Methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 February 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 1), MEDLINE Ovid (1946 to 25 February 2020), Embase Ovid (1980 to 25 February 2020), LILACS BIREME Virtual Health Library (1982 to 25 February 2020) and CINAHL EBSCO (1937 to 25 February 2020). We also searched the VIP Database (January 2012 to 8 March 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

Selection Criteria: We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, gel, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation for at least 48 hours.

Data Collection And Analysis: At least two review authors independently assessed search results, extracted data and assessed risk of bias in included studies. We contacted study authors for additional information. We reported risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, using the random-effects model of meta-analysis when data from four or more trials were combined.

Main Results: We included 40 RCTs (5675 participants), which were conducted in various countries including China, USA, Brazil and Iran. We categorised these RCTs into five main comparisons: chlorhexidine (CHX) mouthrinse or gel versus placebo/usual care; CHX mouthrinse versus other oral care agents; toothbrushing (± antiseptics) versus no toothbrushing (± antiseptics); powered versus manual toothbrushing; and comparisons of other oral care agents used in OHC (other oral care agents versus placebo/usual care, or head-to-head comparisons between other oral care agents). We assessed the overall risk of bias as high in 31 trials and low in two, with the rest being unclear. Moderate-certainty evidence from 13 RCTs (1206 participants, 92% adults) shows that CHX mouthrinse or gel, as part of OHC, probably reduces the incidence of VAP compared to placebo or usual care from 26% to about 18% (RR 0.67, 95% confidence intervals (CI) 0.47 to 0.97; P = 0.03; I = 66%). This is equivalent to a number needed to treat for an additional beneficial outcome (NNTB) of 12 (95% CI 7 to 128), i.e. providing OHC including CHX for 12 ventilated patients in intensive care would prevent one patient developing VAP. There was no evidence of a difference between interventions for the outcomes of mortality (RR 1.03, 95% CI 0.80 to 1.33; P = 0.86, I = 0%; 9 RCTs, 944 participants; moderate-certainty evidence), duration of mechanical ventilation (MD -1.10 days, 95% CI -3.20 to 1.00 days; P = 0.30, I = 74%; 4 RCTs, 594 participants; very low-certainty evidence) or duration of intensive care unit (ICU) stay (MD -0.89 days, 95% CI -3.59 to 1.82 days; P = 0.52, I = 69%; 5 RCTs, 627 participants; low-certainty evidence). Most studies did not mention adverse effects. One study reported adverse effects, which were mild, with similar frequency in CHX and control groups and one study reported there were no adverse effects. Toothbrushing (± antiseptics) may reduce the incidence of VAP (RR 0.61, 95% CI 0.41 to 0.91; P = 0.01, I = 40%; 5 RCTs, 910 participants; low-certainty evidence) compared to OHC without toothbrushing (± antiseptics). There is also some evidence that toothbrushing may reduce the duration of ICU stay (MD -1.89 days, 95% CI -3.52 to -0.27 days; P = 0.02, I = 0%; 3 RCTs, 749 participants), but this is very low certainty. Low-certainty evidence did not show a reduction in mortality (RR 0.84, 95% CI 0.67 to 1.05; P = 0.12, I = 0%; 5 RCTs, 910 participants) or duration of mechanical ventilation (MD -0.43, 95% CI -1.17 to 0.30; P = 0.25, I = 46%; 4 RCTs, 810 participants).

Authors' Conclusions: Chlorhexidine mouthwash or gel, as part of OHC, probably reduces the incidence of developing ventilator-associated pneumonia (VAP) in critically ill patients from 26% to about 18%, when compared to placebo or usual care. We did not find a difference in mortality, duration of mechanical ventilation or duration of stay in the intensive care unit, although the evidence was low certainty. OHC including both antiseptics and toothbrushing may be more effective than OHC with antiseptics alone to reduce the incidence of VAP and the length of ICU stay, but, again, the evidence is low certainty. There is insufficient evidence to determine whether any of the interventions evaluated in the studies are associated with adverse effects.
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http://dx.doi.org/10.1002/14651858.CD008367.pub4DOI Listing
December 2020