Publications by authors named "Jingrui Wang"

37 Publications

E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation.

Am J Transplant 2022 Jun 21. Epub 2022 Jun 21.

Zhejaing University, School of Medicine, Hangzhou, China.

The mammalian target of rapamycin (mTOR) pathway is frequently deregulated and has critical roles in cancer progression. mTOR inhibitor has been widely used in several kinds of cancers and is strongly recommended in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). However, the poor response to mTOR inhibitors due to resistance remains a challenge. Hypoxia-associated resistance limits the therapeutic efficacy of targeted drugs. The present study established models of HCC clinical samples and cell lines resistance to mTOR inhibitor sirolimus and screened out E2F7 as a candidate gene induced by hypoxia and promoting sirolimus resistance. E2F7 suppressed mTOR complex 1 via directly binding to the promoter of the TSC1 gene and stabilizes hypoxia-inducible factor-1α activating its downstream genes, which are responsible for E2F7-dependent mTOR inhibitor resistance. Clinically, low E2F7 expression could be an effective biomarker for recommending patients with HCC for anti-mTOR-based therapies after LT. Targeting E2F7 synergistically inhibited HCC growth with sirolimus in vivo. E2F7 is a promising target to reverse mTOR inhibition resistance. Collectively, our study points to a role for E2F7 in promoting mTOR inhibitor resistance in HCC and emphasizes its potential clinical significance in patients with HCC after LT.
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http://dx.doi.org/10.1111/ajt.17124DOI Listing
June 2022

Biological and molecular characterizations of field fludioxonil-resistant isolates of Fusarium graminearum.

Pestic Biochem Physiol 2022 Jun 19;184:105101. Epub 2022 Apr 19.

State Key Laboratory of Rice Biology, Key Laboratory of Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Fusarium head blight (FHB) predominately caused by F. graminearum, is an economical devastating disease for grain cereal crops especially on wheat. The phenylpyrrole fungicide fludioxonil exhibits excellent activity against F. graminearum and has been registered to control FHB in China. In this study, 6 fludioxonil-resistant (FludR) isolates of F. graminearum were identified from 2910 isolates collected from wheat cultivated field in Jiang Su, An Hui and Henan province of China in 2020. The sensitivity assay showed that resistance factor (RF) of FludR isolates ranges from 170.73 to >1000. In comparison with fludioxonil-sensitive (FludS) isolates, all of FludR isolates showed fitness defects in terms of mycelial growth, conidiation and virulence. Under fludioxonil treatment condition, the glycerol accumulation was obviously increased in FludS isolates, but was slightly increased in FludR isolates. Four FludR isolates exhibited increased sensitivity to osmotic stresses. Moreover, there is no positive cross-resistance between fludioxonil and other fungicides including phenamacril, carbendazim and tebuconazole. When treated with fludioxonil, the phosphorylation level of Hog1 was significantly decreased in the four FludR isolates, which was in contrast to the observation in the FludS and two FludR isolates where phosphorylation level of Hog1 was increased. Sequencing assay showed that the mutations were identified in different domains in FgOS1, FgOS2 or FgOS4 in FludR isolates. This was first reported that biological and molecular characterizations of field isolates of F. graminearum resistant to fludioxonil. The results can provide scientific directions for controlling FHB using fludioxonil.
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http://dx.doi.org/10.1016/j.pestbp.2022.105101DOI Listing
June 2022

Novel γδ T cell-based prognostic signature to estimate risk and aid therapy in hepatocellular carcinoma.

BMC Cancer 2022 Jun 10;22(1):638. Epub 2022 Jun 10.

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No.261, Huansha Road, Zhejiang, Hangzhou, China.

Background: Numerous studies have revealed that gamma delta (γδ) T cell infiltration plays a crucial regulatory role in hepatocellular carcinoma (HCC) development. Nonetheless, a comprehensive analysis of γδ T cell infiltration in prognosis evaluation and therapeutic prediction remains unclear.

Methods: Multi-omic data on HCC patients were obtained from public databases. The CIBERSORT algorithm was applied to decipher the tumor immune microenvironment (TIME) of HCC. Weighted gene co-expression network analysis (WGCNA) was performed to determine significant modules with γδ T cell-specific genes. Kaplan-Meier survival curves and receiver operating characteristic analyses were used to validate prognostic capability. Additionally, the potential role of RFESD inhibition by si-RFESD in vitro was investigated using EdU and CCK-8 assays.

Results: A total of 16,421 genes from 746 HCC samples (616 cancer and 130 normal) were identified based on three distinct cohorts. Using WGCNA, candidate modules (brown) with 1755 significant corresponding genes were extracted as γδ T cell-specific genes. Next, a novel risk signature consisting of 11 hub genes was constructed using multiple bioinformatic analyses, which presented great prognosis prediction reliability. The risk score exhibited a significant correlation with ICI and chemotherapeutic targets. HCC samples with different risks experienced diverse signalling pathway activities. The possible interaction of risk score with tumor mutation burden (TMB) was further analyzed. Subsequently, the potential functions of the RFESD gene were explored in HCC, and knockdown of RFESD inhibited cell proliferation in HCC cells. Finally, a robust prognostic risk-clinical nomogram was developed and validated to quantify clinical outcomes.

Conclusions: Collectively, comprehensive analyses focusing on γδ T cell patterns will provide insights into prognosis prediction, the mechanisms of immune infiltration, and advanced therapy strategies in HCC.
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http://dx.doi.org/10.1186/s12885-022-09662-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185956PMC
June 2022

Management of pancreatic walled-off necrosis using an ultrasonic pneumatic lithotripsy system and double-catheter aspirated lavage performed through drainage tract: a case report.

J Int Med Res 2022 Mar;50(3):3000605221090098

Department of Hepato-pancreato-biliary Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Patients with pancreatic walled-off necrosis (WON) treated by minimally invasive approaches often require repeated necrosectomy instead of conventional open necrosectomy. A 55-year-old woman with lateral infected pancreatic WON was successfully treated by an infrequently used technique involving an ultrasonic pneumatic lithotripsy system (UPLS) and double-catheter aspirated lavage through a percutaneous drainage tract. No perioperative complications occurred. The mean operating time of the repeated procedures was 35 minutes (range, 25-48 minutes). The total hospitalization stay was 46 days, and no recurrence of the fluid collection was observed during the 15-month follow-up period. UPLS-assisted necrosectomy and double-catheter aspirated lavage is an alternative technique for lateral WON that fails to improve by percutaneous drainage. It efficiently combines disintegration and aspiration procedures and can be safely repeated under total intravenous anesthesia through sinus tracts.
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http://dx.doi.org/10.1177/03000605221090098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973053PMC
March 2022

Autophagy-Related Gene Is Involved in Mycelial Growth, Asexual Reproduction and Tolerance to Salt and Oxidative Stresses in  .

Int J Mol Sci 2022 Feb 6;23(3). Epub 2022 Feb 6.

Department of Plant Pathology/Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, Guangzhou 510642, China.

Autophagy is ubiquitously present in eukaryotes. During this process, intracellular proteins and some waste organelles are transported into lysosomes or vacuoles for degradation, which can be reused by the cell to guarantee normal cellular metabolism. However, the function of autophagy-related (ATG) proteins in oomycetes is rarely known. In this study, we identified an autophagy-related gene, encoding a 514-amino-acid protein in which is the most destructive pathogen of litchi. The transcriptional level of was relatively higher in mycelium, sporangia, zoospores and cysts. We generated knockout mutants using CRISPR/Cas9 technology. The Δ mutants were significantly impaired in autophagy and vegetative growth. We further found that the Δ mutants displayed decreased branches of sporangiophore, leading to impaired sporangium production. PlATG6a is also involved in resistance to oxidative and salt stresses, but not in sexual reproduction. The transcription of peroxidase-encoding genes was down-regulated in Δ mutants, which is likely responsible for hypersensitivity to oxidative stress. Compared with the wild-type strain, the Δ mutants showed reduced virulence when inoculated on the litchi leaves using mycelia plugs. Overall, these results suggest a critical role for PlATG6a in autophagy, vegetative growth, sporangium production, sporangiophore development, zoospore release, pathogenesis and tolerance to salt and oxidative stresses in .
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http://dx.doi.org/10.3390/ijms23031839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836449PMC
February 2022

Stereoselective O-Glycosylation of Glycals with Arylboronic Acids Using Air as the Oxygen Source.

Org Lett 2022 03 26;24(8):1587-1592. Epub 2022 Jan 26.

Hubei Key Laboratory of Natural Products Research and Development, Key Laboratory of Functional Yeast (China National Light Industry), College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, P. R. China.

An open-air palladium-catalyzed O-glycosylation was developed using glycals and arylboronic acids with base additives at ambient conditions. The novel approach enabled facile access to various -glycosides in high yields, with exclusive 1,4--stereoselectivity tolerating reactive hydroxyl/amino groups. Mechanistic studies indicated that chemo-/stereoselectivity arose from the coordination between palladium and phenols generated by oxidizing arylboronic acids, followed by an intramolecular attack. Isotope-labeling experiments revealed that the oxygen of O-glycosidic bonds came from O.
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http://dx.doi.org/10.1021/acs.orglett.1c04378DOI Listing
March 2022

Fusarium graminearum FgSdhC1 point mutation A78V confers resistance to the succinate dehydrogenase inhibitor pydiflumetofen.

Pest Manag Sci 2022 May 31;78(5):1780-1788. Epub 2022 Jan 31.

State Key Laboratory of Rice Biology, Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.

Background: Fusarium head blight (FHB) caused by Fusarium graminearum complex (Fg) is a devastating disease of cereal crops worldwide. The succinate dehydrogenase inhibitor, pydiflumetofen, was registered for management of FHB in China in 2019. Previously, laboratory-induced pydiflumetofen-resistant (PyR) mutants of Fg have been characterized. However, resistance situation of Fg to pydiflumetofen in the field remains largely unknown.

Results: After screening 6468 isolates of Fg from various regions of China, six PyR isolates were identified. All six resistant isolates exhibited no fitness penalties based on mycelial growth, conidiation and virulence. However, no cross-resistance between pydiflumetofen and azoxystrobin, tebuconazole or fludioxonil in Fg was detected. Genome-sequencing revealed that all six PyR isolates contained a point mutation A78V in FgSdhC1 (FgSdhC1 ). Genetic replacement assay further confirmed that FgSdhC1 conferred resistance of Fg to pydiflumetofen. Based on this, a mismatch allele-specific polymerase chain reaction was developed for rapidly detecting the PyR isolates containing the FgSdhC1 mutation in Fg.

Conclusion: This is the first time that resistance of Fg to pydiflumetofen in the field was reported and point mutation FgSdhC1 conferring resistance of Fg to pydiflumetofen was confirmed. This study provides critical information for monitoring and managing pydiflumetofen resistance in Fg.
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http://dx.doi.org/10.1002/ps.6795DOI Listing
May 2022

Comparison of several blood lipid-related indexes in the screening of non-alcoholic fatty liver disease in women: a cross-sectional study in the Pearl River Delta region of southern China.

BMC Gastroenterol 2021 Dec 19;21(1):482. Epub 2021 Dec 19.

Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China.

Background: Lipid metabolism disorders play a critical role in the progression of non-alcoholic fatty liver disease (NAFLD). However, the number of studies on the relationships among blood lipid-related indexes and NAFLD is limited, and few studies have emphasized the comparison of blood lipid-related indexes in the same population to identify the optimal index for NAFLD screening. This study aimed to investigate the relationships among several blood lipid-related indexes and NAFLD, and to find the index with the best screening value for NAFLD.

Methods: Based on a general health examination at community health service agencies in the Pearl River Delta region of China in 2015, 3239 women were recruited in this cross-sectional study. The relationships among blood lipid-related indexes and NAFLD were assessed separately by constructing multivariate logistic regression models. Receiver operating characteristic analysis was used to evaluate and compare the screening abilities of the indexes for NAFLD. All data analyses were conducted in SPSS and MedCalc software.

Results: Whether in the crude model or each model adjusted for possible confounding factors, the risk of NAFLD significantly rose with increasing cardiometabolic index (CMI), triglyceride glucose index (TyG), triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C), total cholesterol (TC) to HDL-C ratio (TC/HDL-C) and low-density lipoprotein (LDL-C) to HDL-C ratio (LDL-C/HDL-C). Moreover, the area under the curve (AUC) of CMI was 0.744, which was better than that of TyG (0.725), TG/HDL-C (0.715), TC/HDL-C (0.650), and LDL-C/HDL-C (0.644) (P < 0.001). In addition, the optimal cut-off points were 0.62 for CMI, 8.55 for TyG, 1.15 for TG/HDL-C, 4.17 for TC/HDL-C, and 2.22 for LDL-C/HDL-C.

Conclusions: CMI is easy to obtain, is a recommended index in the screening of NAFLD in women and may be useful for detecting populations that are at high risk of NAFLD.
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http://dx.doi.org/10.1186/s12876-021-02072-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684623PMC
December 2021

Design, synthesis, and evaluation of potent RIPK1 inhibitors with in vivo anti-inflammatory activity.

Eur J Med Chem 2022 Jan 8;228:114036. Epub 2021 Dec 8.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, PR China. Electronic address:

RIPK1 plays a key role in the necroptosis pathway that regulates inflammatory signaling and cell death in various diseases, including inflammatory and neurodegenerative diseases. Herein, we report a series of potent RIPK1 inhibitors, represented by compound 70. Compound 70 efficiently blocks necroptosis induced by TNFα in both human and mouse cells (EC = 17-30 nM). Biophysical assay demonstrates that compound 70 potently binds to RIPK1 (K = 9.2 nM), but not RIPK3 (K > 10,000 nM). Importantly, compound 70 exhibits greatly improved metabolic stability in human and rat liver microsomes compared to compound 6 (PK68), a RIPK1 inhibitor reported in our previous work. In addition, compound 70 displays high permeability in Caco-2 cells and excellent in vitro safety profiles in hERG and CYP assays. Moreover, pre-treatment of 70 significantly ameliorates hypothermia and lethal shock in SIRS mice model. Lastly, compound 70 possesses favorable pharmacokinetic parameters with moderate clearance and good oral bioavailability in SD rat. Taken together, our work supports 70 as a potent RIPK1 inhibitor and highlights its potential as a prototypical lead for further development in necroptosis-associated inflammatory disorders.
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http://dx.doi.org/10.1016/j.ejmech.2021.114036DOI Listing
January 2022

Effects of active vitamin D on insulin resistance and islet β-cell function in non-diabetic chronic kidney disease patients: a randomized controlled study.

Int Urol Nephrol 2022 Jul 22;54(7):1725-1732. Epub 2021 Nov 22.

Department of Nephrology, People's Hospital of Yuxi City, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, 653100, Yunnan Province, China.

Purpose: The purpose of the study is to observe the effects of active vitamin D supplementation on insulin resistance and islet β-cell function (HOMA-β) in patients with non-diabetic chronic kidney disease (NDCKD).

Methods: A total of 134 patients with NDCKD who met the inclusion criteria were enrolled in the prospective controlled study and categorized as such: 60 patients in the non-dialysis (ND) group; 36, hemodialysis (HD) group; and 38, peritoneal dialysis (PD) group. Each group was divided into two equal-numbered subgroups for vitamin D supplementation. Those in the experimental subgroups received calcitriol 0.5 ug/day orally, and were followed-up for 6 months. A total of 117 patients were followed-up, including 57 patients in the ND group; 29, HD group; and 31, PD group. Changes in the insulin resistance index (HOMA-IR) and HOMA-β index were calculated and compared at the time of enrollment and after 1, 3, and 6 months of intervention.

Results: (1) Mean HOMA-IR value: In the ND group, mean HOMA-IR value of the experimental group significantly decreased compared with that of the control group after 3 months of intervention (P = 0.02). In the HD and PD groups, there was no statistical difference between the experimental and control groups (P > 0.05). (2) Mean HOMA-β index: In the ND group, mean HOMA-β index of the experimental group was higher than that of the control group after 1 month of active vitamin D treatment (P = 0.03), and, with an extended intervention time, the index gradually increased (P < 0.001). In the HD group, mean HOMA-β index of the experimental group was higher than that of the control group after 3 months of active vitamin D treatment (P = 0.01). Among PD patients, mean HOMA-β index of the patients in the experimental group was higher than that of the control group after 6 months of active vitamin D treatment (P = 0.02).

Conclusions: Active vitamin D supplementation improved insulin resistance and HOMA-β after 6 months in ND patients, but only improved HOMA-β in the dialysis patients, with no significant effect on insulin resistance.
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http://dx.doi.org/10.1007/s11255-021-02968-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184423PMC
July 2022

Inhibition Effect of Solid Products and DC Breakdown Characteristics of the HFO1234Ze(E)-N-O Ternary Gas Mixture.

ACS Omega 2021 Sep 31;6(36):23281-23292. Epub 2021 Aug 31.

Advanced High Voltage Engineering Research Centre, Cardiff University, Cardiff, Wales CF24 3AA, United Kingdom.

HFO1234ze(E) is an environmentally friendly SF substitute gas with prominent application potential. To suppress the generation of the HFO1234ze(E) solid decomposition products, which may cause great hazards to the gas-solid insulation strength, a gas mixing scheme screening method based on the reactive force field (ReaxFF) molecular dynamics (MD) simulation was innovatively proposed. The simulation results show that the inhibitory effect of O on the formation of HFO1234ze(E) solid products is better than those of CO and CF. Further study shows that when O accounts for 3.33% of the gas mixture, the solid precipitate content is reduced by 48%. The experimental study shows that an O content of 3.33% can inhibit the generation of solid products by more than 50%. Besides, compared with HFO1234ze(E)-N, the DC breakdown voltage of HFO1234ze(E)-N-O is slightly increased, and the breakdown voltage dispersion degree and continuous breakdown voltage drop rate are decreased. This work gives a feasible solution for the suppression of HFO1234ze(E) solid decomposition products and provides an efficient method for solving similar problems of environmentally friendly insulating gas in C/F/O/N systems.
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http://dx.doi.org/10.1021/acsomega.1c03020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444307PMC
September 2021

Emerging Artificial Neuron Devices for Probabilistic Computing.

Front Neurosci 2021 6;15:717947. Epub 2021 Aug 6.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, China.

In recent decades, artificial intelligence has been successively employed in the fields of finance, commerce, and other industries. However, imitating high-level brain functions, such as imagination and inference, pose several challenges as they are relevant to a particular type of noise in a biological neuron network. Probabilistic computing algorithms based on restricted Boltzmann machine and Bayesian inference that use silicon electronics have progressed significantly in terms of mimicking probabilistic inference. However, the quasi-random noise generated from additional circuits or algorithms presents a major challenge for silicon electronics to realize the true stochasticity of biological neuron systems. Artificial neurons based on emerging devices, such as memristors and ferroelectric field-effect transistors with inherent stochasticity can produce uncertain non-linear output spikes, which may be the key to make machine learning closer to the human brain. In this article, we present a comprehensive review of the recent advances in the emerging stochastic artificial neurons (SANs) in terms of probabilistic computing. We briefly introduce the biological neurons, neuron models, and silicon neurons before presenting the detailed working mechanisms of various SANs. Finally, the merits and demerits of silicon-based and emerging neurons are discussed, and the outlook for SANs is presented.
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http://dx.doi.org/10.3389/fnins.2021.717947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377243PMC
August 2021

Hybrid oxide brain-inspired neuromorphic devices for hardware implementation of artificial intelligence.

Sci Technol Adv Mater 2021 May 14;22(1):326-344. Epub 2021 May 14.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, China.

The state-of-the-art artificial intelligence technologies mainly rely on deep learning algorithms based on conventional computers with classical von Neumann computing architectures, where the memory and processing units are separated resulting in an enormous amount of energy and time consumed in the data transfer process. Inspired by the human brain acting like an ultra-highly efficient biological computer, neuromorphic computing is proposed as a technology for hardware implementation of artificial intelligence. Artificial synapses are the main component of a neuromorphic computing architecture. Memristors are considered to be a relatively ideal candidate for artificial synapse applications due to their high scalability and low power consumption. Oxides are most widely used in memristors due to the ease of fabrication and high compatibility with complementary metal-oxide-semiconductor processes. However, oxide memristors suffer from unsatisfactory stability and reliability. Oxide-based hybrid structures can effectively improve the device stability and reliability, therefore providing a promising prospect for the application of oxide memristors to neuromorphic computing. This work reviews the recent advances in the development of hybrid oxide memristive synapses. The discussion is organized according to the blending schemes as well as the working mechanisms of hybrid oxide memristors.
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http://dx.doi.org/10.1080/14686996.2021.1911277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128179PMC
May 2021

The Mitogen-Activated Protein Kinase PlMAPK2 Is Involved in Zoosporogenesis and Pathogenicity of .

Int J Mol Sci 2021 Mar 29;22(7). Epub 2021 Mar 29.

Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Department of Plant Pathology, South China Agricultural University, Guangzhou 510642, China.

As an evolutionarily conserved pathway, mitogen-activated protein kinase (MAPK) cascades function as the key signal transducers that convey information by protein phosphorylation. Here we identified as one of 14 predicted MAPKs encoding genes in the plant pathogenic oomycete . is conserved in and species. We found that was up-regulated in sporangium, zoospore, cyst, cyst germination and early stage of infection. We generated knockout mutants using the CRISPR/Cas9 method. Compared with wild-type strain, the mutants showed no significant difference in vegetative growth, oospore production and sensitivity to various abiotic stresses. However, the sporangium release was severely impaired. We further found that the cleavage of the cytoplasm into uninucleate zoospores was disrupted in the mutants, and this developmental phenotype was accompanied by reduction in the transcription levels of and genes. Meanwhile, the mutants exhibited lower laccase activity and reduced virulence to lychee leaves. Overall, this study identified a MAPK that is critical for zoosporogenesis by regulating the sporangial cleavage and pathogenicity of , likely by regulating laccase activity.
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http://dx.doi.org/10.3390/ijms22073524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036616PMC
March 2021

Short chain fatty acids inhibit endotoxin-induced uveitis and inflammatory responses of retinal astrocytes.

Exp Eye Res 2021 05 20;206:108520. Epub 2021 Feb 20.

Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY, USA. Electronic address:

Short chain fatty acids (SCFAs) are produced by gut microbiota as fermentation products of digestion-resistant oligosaccharides and fibers. Their primary roles are functioning as major energy sources for colon cells and assisting in gut homeostasis by immunomodulation. Recent evidence suggests that they affect various organs both at cellular and molecular levels, and regulate functions in distance sites including gene expression, cell proliferation, cell differentiation, apoptosis and inflammation. In this study, we examined whether SCFAs are present in the mouse eye and whether SCFAs affect inflammatory responses of the eye and retinal astrocytes (RACs). We observed that intra-peritoneal injected SCFAs were detected in the eye and reduced intraocular inflammation induced by lipopolysaccharide (LPS). Moreover, SCFAs displayed two disparate effects on LPS-stimulated RACs - namely, cytokine and chemokine production was reduced, but the ability to activate T cells was enhanced. Our results support the existence of gut-eye cross talk and suggest that SCFAs can cross the blood-eye-barrier via the systemic circulation. If applied at high concentrations, SCFAs may reduce inflammation and impact cellular functions in the intraocular milieu.
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http://dx.doi.org/10.1016/j.exer.2021.108520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489808PMC
May 2021

Discovery of a Potent RIPK3 Inhibitor for the Amelioration of Necroptosis-Associated Inflammatory Injury.

Front Cell Dev Biol 2020 8;8:606119. Epub 2020 Dec 8.

Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medial College, Beijing, China.

Necroptosis is a form of regulated necrosis that requires the activation of receptor-interacting kinase 3 (RIPK3 or RIP3) and its phosphorylation of the substrate MLKL (mixed lineage kinase domain-like protein). Necroptosis has emerged as important cell death involved in the pathogenesis of various diseases including inflammatory diseases, degenerative diseases, and cancer. Here, we discovered a small molecule Zharp-99 as a potent inhibitor of necroptosis through blocking the kinase activity of RIPK3. Zharp-99 efficiently blocks necroptosis induced by ligands of the death receptor and Toll-like receptor as well as viral infection in human, rat and mouse cells. Zharp-99 strongly inhibits cellular activation of RIPK3, and MLKL upon necroptosis stimuli. Zharp-99 directly blocks the kinase activity of RIPK3 without affecting RIPK1 kinase activity at the tested concentration. Importantly, Zharp-99 exerts effective protection against TNF-α induced systemic inflammatory response syndrome in the mouse model. Zharp-99 displays favorable safety profiles and pharmacokinetic parameters. Thus, our study demonstrates Zharp-99 as a potent inhibitor of RIPK3 kinase and also highlights its potential for further development of new approaches for treating necroptosis-associated inflammatory disorders.
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http://dx.doi.org/10.3389/fcell.2020.606119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753040PMC
December 2020

Study on Pyrolysis Characteristics of SF in a Trace-Oxygen (O) Environment: ReaxFF Force Field Optimization and Reactive Molecular Dynamics Simulation.

ACS Omega 2020 Oct 6;5(41):26518-26526. Epub 2020 Oct 6.

Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing 102206, China.

The ReaxFF force field for a SF-O system is developed based on the density functional theory (DFT) calculation data. Then, a series of molecular dynamics (MD) simulations were performed. The results show that the main oxygen-containing compounds that appeared in the MD simulation include SOF, SOF, and SOF. The relative quantitative relationship between SOF and SOF can be used to determine the fault temperature. Besides, under overheating conditions, O rarely undergoes a self-cracking process to generate free O atoms. Instead, the basic route for O to participate in the SF pyrolysis process is X + Y + O = XO + YO. Furthermore, the reactivity order of various groups to O is (SF)* > (SF)* > (SF)* > F*, so O is more likely to participate in the reaction by attacking (SF)* or (SF)* groups. This study laid the foundation for the application of ReaxFF MD simulations to study the microscopic dynamic mechanism of SF pyrolysis in more complex systems.
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http://dx.doi.org/10.1021/acsomega.0c03214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581245PMC
October 2020

Theoretical and experimental investigation on decomposition mechanism of eco-friendly insulation gas HFO1234zeE.

J Mol Graph Model 2020 11 8;100:107671. Epub 2020 Jul 8.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing, 102206, PR China.

Decomposition experiments under corona discharge and theoretical calculations using the density functional theory (DFT) method were accomplished to clarify the dissociation behavior and decomposition mechanism of HFO1234zeE (trans-1,3,3,3-tetrafluoropropene), an eco-efficient SF alternative gas. The discharge decomposition products of HFO are mainly fluorocarbon, unsaturated hydrocarbon and saturated hydrocarbons, which are containing no more than three carbons. Free radicals, CF·, F· and H·, generated via bond-cleavage reaction are important structures to promote the decomposition, and HFO is more likely to dissociate with them by abstraction reaction to form CF and CFH. Long-chain radicals, such as CFCHCF·, CFCHCH· and CFCCHF·, will be decomposed into CFCCH and CFCCF, and small intermediates would be easier to combine to form HF, CF, CF, CHF, CFHCFH and CF. It is also likely to be converted to Z-isomer. Due to the high discharge intensity and ion bombardment, solid by-products appeared on the electrode surface may contain carbon dust and metal compounds. The solid attached to the surface has little effect on the electric field distribution, and most gas decomposition products still maintain the insulation strength, so the air-gap breakdown voltage only dropped by about 6.2% after long-term corona discharge. The obtained results not only reveal the decomposition mechanism in a comprehensive way, but also present useful reference for exploring the application potentials of HFO1234zeE.
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http://dx.doi.org/10.1016/j.jmgm.2020.107671DOI Listing
November 2020

Detection of microRNA-335-5p on an Interdigitated Electrode Surface for Determination of the Severity of Abdominal Aortic Aneurysms.

Nanoscale Res Lett 2020 May 11;15(1):105. Epub 2020 May 11.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.

Abdominal aortic aneurysm (AAA) refers to the enlargement of the lower artery of the abdominal aorta, and identification of an early detection tool is urgently needed for diagnosis. In the current study, an interdigitated electrode (IDE) sensing surface was used to identify miRNA-335-5p, which reflects the formation of AAAs. The uniformity of the silica material was observed by 3D profilometry, and the chemically modified highly conductive surface improved the detection via the I-V mode. The targeted miRNA-335-5p was detected in a dose-dependent manner and based on linear regression and 3σ analyses, the sensitivity was determined to be 1 fM with a biotinylated probe. The high specificity was shown by discriminating the target sequence from noncomplementary and single- and triple-mismatched sequences. These outputs demonstrated the high-performance detection of miRNA-335-5p with good reproducibility for determination of the severity of AAA.
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http://dx.doi.org/10.1186/s11671-020-03331-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214562PMC
May 2020

Anti-CRISPRs: Protein Inhibitors of CRISPR-Cas Systems.

Annu Rev Biochem 2020 06 18;89:309-332. Epub 2020 Mar 18.

RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; email:

Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying (CRISPR-associated) genes are found frequently in bacteria and archaea, serving to defend against invading foreign DNA, such as viral genomes. CRISPR-Cas systems provide a uniquely powerful defense because they can adapt to newly encountered genomes. The adaptive ability of these systems has been exploited, leading to their development as highly effective tools for genome editing. The widespread use of CRISPR-Cas systems has driven a need for methods to control their activity. This review focuses on anti-CRISPRs (Acrs), proteins produced by viruses and other mobile genetic elements that can potently inhibit CRISPR-Cas systems. Discovered in 2013, there are now 54 distinct families of these proteins described, and the functional mechanisms of more than a dozen have been characterized in molecular detail. The investigation of Acrs is leading to a variety of practical applications and is providing exciting new insight into the biology of CRISPR-Cas systems.
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http://dx.doi.org/10.1146/annurev-biochem-011420-111224DOI Listing
June 2020

miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1.

J Cell Biochem 2019 10 12;120(10):17650-17661. Epub 2019 Jun 12.

Department of Radiotherapy, Tianjin Medical University Second Hospital, Tianjin, China.

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by high cellular proliferation and early distant metastasis. Our study aimed to explore the effect of miR-22-3p (miR-22, for short) on SCLC radiosensitivity and its molecular mechanisms. The expression level of miR-22 was evaluated in a human normal lung epithelial cell line and a human SCLC cell line, and cell apoptosis and migration were detected. The expression of the miR-22 direct target WRNIP1 mRNA and protein were explored. Five differentially expressed genes were detected. The miR-22 expression in NCI-H446 was significantly decreased, and miR-22 overexpression significantly promoted cell apoptosis. miR-22 overexpression could significantly inhibit the cell migration of SCLC cells, and miR-22 had a negative regulatory effect on WRNIP1 mRNA and protein levels. KLK8 was downregulated, and the messenger RNA (mRNA) of four other genes (PC, SCUBE1, STC1, and GPM6A) was upregulated mRNA in cells overexpressing miR-22, which was in accordance with the bioinformatics analysis. miR-22 could enhance the radiosensitivity of SCLC by targeting WRNIP1.
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http://dx.doi.org/10.1002/jcb.29032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771739PMC
October 2019

Voltammetric determination of the Alzheimer's disease-related ApoE 4 gene from unamplified genomic DNA extracts by ferrocene-capped gold nanoparticles.

Mikrochim Acta 2018 11 14;185(12):549. Epub 2018 Nov 14.

Department oft of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, People's Republic of China.

A sensitive method is described for detection of the apoE 4 gene detection which is important for early diagnosis of Alzheimer's disease. It is based on signal amplification by using ferrocene (Fc) capped gold nanoparticles modified with streptavidin. The immobilized oligonucleotide probe captures complementary apoE 4 gene. This is followed by the specific recognition of the GCGC sequences which are hydrolyzed by the restriction enzyme HhaI. Cleavage only occurs at the complementary apoE 4 duplex, while mismatches prevent enzymatic cleavage. Thus, the apoE 4 sequence can be discriminated against other apoE sequences. Benefitting from amplified signal by Fc-capped nanoparticle/streptavidin and the recognition of HhaI, the detection limit is as low as 0.1 pM of the ApoE 4 gene. Four genomic DNA samples extracted from blood were analyzed for the presence of the apoE 4 gene. The approach presented here will provide viable proof-of-principle for an enzyme-assisted electrochemical assay for the apoE 4 gene in genomic DNAs. Graphical abstract Schematic presentation of amplified voltammetric detection of Alzheimer's Disease-related apoE 4 gene from unamplified genomic DNA extracts via ferrocene capped gold nanoparticle/streptavidin.
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http://dx.doi.org/10.1007/s00604-018-3087-9DOI Listing
November 2018

Echocardiographic characteristics of primary malignant pericardial mesothelioma and outcomes analysis: a retrospective study.

Cardiovasc Ultrasound 2018 Apr 26;16(1). Epub 2018 Apr 26.

Echocardiography Department of Heart Center, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China.

Background: Little is known about the echocardiographic characteristics of primary malignant pericardial mesothelioma (PPM) due to its rarity. The aim of this study was to explore the sex-specific echocardiographic patterns of PPM and risk factors for in-hospital mortality.

Methods: A retrospective information retrieval was conducted for cases of PPM reported from China during 1981 and 2015. The diagnosis was made by histopathological examinations and only cases with echocardiographic descriptions were included. Data on the clinical and echocardiographic findings were collected. Difference in clinical, sex-specific echocardiographic characteristics and findings across different time periods were assessed. Logistic regression analysis was performed to explore echocardiographic risk factors for in-hospital mortality.

Results: A total of 64 patients with PPM were included, with a mean age of 39.2 ± 15.6 years and minor male dominance (40, 62.5%). The most common echocardiographic presentations were pericardial effusion (55, 85.9%), pericardial masses (36.4%) and thickening (17.3%), respectively. The positive rate of pericardiocentesis was only 20.9%. Six patients (15.4%) died among 39 cases reporting in-hospital outcome. Logistics analysis identified no clinical or echocardiographic parameters associated with in-hospital mortality (all P > 0.05).

Conclusions: The echocardiographic signs of PPM are basically nonspecific with massive pericardial effusion as the most common sign, although no echocardiographic gender differences or association with in-hospital mortality could be identified.
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http://dx.doi.org/10.1186/s12947-018-0125-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922299PMC
April 2018

Downregulation of PRAME Suppresses Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma Through the Activation of P53 Mediated Pathway.

Cell Physiol Biochem 2018 7;45(3):1121-1135. Epub 2018 Feb 7.

Background/aims: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism.

Methods: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro. Further, we examined the relationship between PRAME and p53 pathway in vitro by using Western blotting. Finally, PRAME expression was detected to evaluate its correlation with p-p53 and p53 pathway related apoptotic proteins in xenograft tumor mouse model using immunohistochemistry.

Results: PRAME expression was significantly higher in HCC tissues than in adjacent non-tumor tissues and their expression was positively correlated with alpha fetoprotein levels and tumor size. In addition, PRAME expression was associated with AJCC stage and is a potential biomarker of poor prognosis regarding 5-year overall survival in HCC. In vitro studies, we found that PRAME expression was higher in HCC cell lines than in normal hepatic cell line. Inhibited cell proliferation and increased cell apoptosis was observed in PRAME knockdown HCC cells. Futher, increased cell apoptosis was correlated with the proportion of cells in G0/G1 stage, activated p53 mediated apoptosis, and increased cyclin p21 expression. Xenograft analysis in nude mice also found that PRAME knockdown inhibited tumorigenesis while PRAME overexpression had opposite effect.

Conclusions: In HCC, PRAME serves as a potential biomarker for poor prognosis and novel therapeutic target in treating this cancer. PRAME is a potential biomarker of poor prognosis in HCC. PRAME surpresses HCC cell death in vitro and in vivo by regulating p53 apoptotic signaling and may serve as a potential therapeutic target in HCC.
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http://dx.doi.org/10.1159/000487353DOI Listing
March 2018

Multiplexed Electrochemical Detection of MiRNAs from Sera of Glioma Patients at Different Stages via the Novel Conjugates of Conducting Magnetic Microbeads and Diblock Oligonucleotide-Modified Gold Nanoparticles.

Anal Chem 2017 10 5;89(20):10834-10840. Epub 2017 Oct 5.

College of Chemistry and Chemical Engineering, Central South University , Changsha, Hunan 410083, P. R. China.

MicroRNAs (miRNAs) serve as diagnostic and prognostic biomarkers for a wide variety of cancers. Via the novel conjugates of gold nanoparticle-coated magnetic microbeads (AuNP-MMBs) and the diblock oligonucleotide (ODN)-modified AuNPs, multiplexed electrochemical assay of miRNAs was performed. The hybridization to target miRNAs leads to the conformational change of the hairpin-structured ODN probes, and the attachment of the diblock ODN-modified AuNPs was achieved. By examining the oxidation peak currents of methylene blue (MB) and ferrocene (Fc) moieties residing on the diblock ODNs, simultaneous quantification of miRNA-182 and miRNA-381 was conducted. The detection signals were significantly enhanced due to the numerous MB and Fc tags on the AuNPs. The proposed assay was highly selective for discriminating miRNAs with similar sequences, and detection limits of 0.20 fM and 0.12 fM for miRNA-182 and miRNA-381, respectively, were achieved. The feasibility of the method for sensitive determination of miRNA-182 and miRNA-381 from serum samples of glioma patients at different stages was demonstrated. The sensing protocol thus holds great potential for early diagnosis and treatment of cancer patients.
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http://dx.doi.org/10.1021/acs.analchem.7b02342DOI Listing
October 2017

Identification of key mRNAs and microRNAs in the pathogenesis and progression of osteoarthritis using microarray analysis.

Mol Med Rep 2017 Oct 14;16(4):5659-5666. Epub 2017 Aug 14.

Department of Orthopedics, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Osteoarthritis (OA) is a common type of disease affecting the joints that results from the breakdown of joint cartilage and the underlying bone; currently, its pathogenesis is still unclear. The aim of the present study was to identify key mRNAs and miRNAs involved in the pathogenesis and progression of OA using microarray analysis. The gene expression profile of GSE27492 was downloaded from the Gene Expressed Omnibus database, and included 49 arthritic mouse ankle samples collected at 6 time points (0, 1, 3, 7, 12 and 18 days) following the induction of arthritis via serum transfer. Differentially expressed genes (DEGs) were identified in ankle samples taken on days 1, 3, 7, 12 and 18 following serum transfer compared with day 0 samples, and overlapping DEGs in day 3, 7, 12 and 18 samples were identified. The Database for Annotation, Visualization and Integrated Discovery online tool was used to perform functional and pathway enrichment analyses of the overlapping DEGs. The miRWalk database was used to identify potential micro (mi) RNAs regulating the selected overlapping DEGs, and regulatory miRNA‑target mRNA pairs were obtained. The Cytoscape platform was used to establish and visualize the miRNA‑mRNA regulatory network. The present results revealed that 35, 103, 62 and 75 DEGs were identified in day 3, 7, 12 and 18 samples, respectively. A total of 17 overlapping DEGs were identified among the 4 sample sets, and revealed to be enriched in 14 gene ontology terms and 3 Kyoto Encyclopedia of Genes and Genomes pathways. miRWalk analysis identified 242 potential miRNA‑mRNA regulatory pairs and 211 nodes were revealed to be involved in the miRNA‑mRNA regulatory network. The present study identified potential genes, including C‑type lectin domain family 4 member D, chemokine (C‑X‑C motif) ligand 1 and C‑C motif chemokine ligand, and pathways, including chemokine signaling pathways, cytokine‑cytokine receptor interactions and nucleotide‑binding oligomerization domain‑like receptor signaling pathways, which may be involved in the pathogenesis and progression of OA. These findings may help elucidate the molecular mechanisms underlying OA pathophysiology, and may be useful for the development of novel therapeutic targets for the treatment of patients with OA.
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http://dx.doi.org/10.3892/mmr.2017.7251DOI Listing
October 2017

Ultrasensitive Memristive Synapses Based on Lightly Oxidized Sulfide Films.

Adv Mater 2017 Jun 11;29(24). Epub 2017 Apr 11.

Key Laboratory of Graphene Technologies and Applications of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China.

For biological synapses, high sensitivity is crucial for transmitting information quickly and accurately. Compared to biological synapses, memristive ones show a much lower sensitivity to electrical stimuli since much higher voltages are needed to induce synaptic plasticity. Yet, little attention has been paid to enhancing the sensitivity of synaptic devices. Here, electrochemical metallization memory cells based on lightly oxidized ZnS films are found to show highly controllable memristive switching with an ultralow SET voltage of several millivolts, which likely originates from a two-layer structure of ZnS films, i.e., the lightly oxidized and unoxidized layers, where the filament rupture/rejuvenation is confined to the two-layer interface region several nanometers in thickness due to different ion transport rates in these two layers. Based on such devices, an ultrasensitive memristive synapse is realized where the synaptic functions of both short-term plasticity and long-term potentiation are emulated by applying electrical stimuli several millivolts in amplitude, whose sensitivity greatly surpasses that of biological synapses. The dynamic processes of memorizing and forgetting are mimicked through a 5 × 5 memristive synapse array. In addition, the ultralow operating voltage provides another effective solution to the relatively high energy consumption of synaptic devices besides reducing the operating current and pulse width.
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http://dx.doi.org/10.1002/adma.201606927DOI Listing
June 2017

Analysis of learning curve for laparoscopic pancreaticoduodenectomy.

J Vis Surg 2016 18;2:145. Epub 2016 Aug 18.

Department of General Surgery, School of Medicine, Zhejiang University, Hangzhou 310058, China.

Background: Laparoscopic pancreaticoduodenectomy (LPD) may have potential minimal invasive advantages for selected patients in limited center. However, few studies analyzed the learning curve. This study aimed to analyze the learning curve of this procedure at a large volume set, and share our experience to surmount it.

Methods: All prospectively maintained data of the consecutive LPDs was reviewed retrospectively. The procedures were performed by single surgeon. Patients were divided into four groups according to staged approach with different focuses: Group A (the first 30 patients), Group B (the second 30 patients), Group C (the third 30 patients), and Group D (the fourth and last 30 patients). And the changes of outcomes during different learning periods were analyzed.

Results: Between September 2012 and July 2015, 120 patients underwent LPD. One hundred and eleven of them underwent totally LPD, and 9 patients underwent laparoscopic assisted pancreaticoduodenectomy (LAPD). The mean operative time (OT), mean blood loss and average length of hospital stay (LOS) was 359.8±57.6 min, 169.7±152.6 mL and 17.0±9.8 d respectively. A total of 42 (35%) patients developed morbidity with no mortality. The mean overall OT tended to decrease from 370.2±52.8 min in Group A to 342.0±73.1 min in Group D with the accumulating experience of the surgeon. Moreover, mean OT of pancreatojejunostomy and choledochojejunostomy also tended to decrease from 55.0±8.7, 39.8±11.7 min in Group A to 43.6±7.6, 27.7±11.8 min in Group D respectively. Meanwhile, the clinical outcomes tended to get better. Mean blood loss, morbidity and LOS decreased from 219.3±147.9 mL, 43.3%, 18.7±10.0 d in Group A to 140.1±73.6 mL, 23.3%, 14.4±6.2 d in Group C respectively except for Group D.

Conclusions: Routine practice of the LPD procedure was feasible and safe. Gained experience can improve clinical outcomes in 30 to 60 operations by overcoming the learning curve.
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http://dx.doi.org/10.21037/jovs.2016.07.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637755PMC
August 2016

[Identification of a new probiotic Lactobacillus alimentarius W369 from Chinese traditional pickles].

Wei Sheng Wu Xue Bao 2016 Jun;56(6):932-42

Objective: A new lactic acid bacterium was isolated from Chinese traditional pickles and its potential probiotic properties were analyzed.

Methods: The strain was identified by morphological observation, physiological and biochemical tests and 16S rRNA gene comparison. Its probiotic properties were evaluated, including resistance to NaCl, the minimum inhibitory concentration of antibiotics, nitrite degradation ability and cholesterol removal ability.

Results: This strain was identified as Lactobacillus alimentarius W369 (No. CGMCC 7.180). L. alimentarius W369 could survive under the concentration of 10% NaCl and it was sensitive to some common antibiotics. By studying its probiotic properties, we found that its nitrite degradation rate reached 92.92% after 72 h and the cholesterol removal rate reached 31.80%. The fermented supernatant showed strong abilities of DPPH· and the superoxide anion radical scavenging capacity, as well as Fe2+ chelating ability. The clearance rate were (88.02±1.48)%, (43.75±3.10)% and (29.99±2.34)% respectively. Strain W369 also exhibited strong reducing capacity, hydroxyl radical scavenging action and lipid peroxidation inhibition capacity. Both the fermented supernatant and cell-free extracts exhibited glutathione peroxidase (GSH-Px) and superoxide dismutase (Mn-SOD) activities.

Conclusion: L. alimentariusW369 possessed many probiotic properties including nitrite degradation ability, cholesterol removal ability and antioxidant activity. It has many potential application values.
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June 2016

Determinants and influencing mechanism of outpatient satisfaction: a survey on tertiary hospitals in the People's Republic of China.

Patient Prefer Adherence 2016 21;10:601-12. Epub 2016 Apr 21.

Institute of Military Health Management, Second Military Medical University, Shanghai, People's Republic of China.

Objective: Most patients in the People's Republic of China prefer tertiary hospitals when seeking medical services. The aim of this study was to assess outpatient satisfaction with tertiary hospitals in the People's Republic of China, test overall and subscale satisfaction, and explore whether sociodemographic characteristics lead to different degrees of satisfaction and whether subscale outpatient satisfaction contributes to overall satisfaction.

Methods: A closed questionnaire was given out to investigate outpatients' sociodemographic characteristics, overall satisfaction, and various subtypes of satisfaction, and a 5-point Likert scale was employed to measure the degree of outpatient satisfaction. Descriptive analysis, Kruskal-Wallis test, Spearman's rank correlation coefficient, and logistic regression analysis were employed for statistical analysis.

Results: Response rate was 92.48% (971/1,050). Outpatients' sociodemographic characteristics (including sex, age, occupation, monthly income, residence, and marital status) were related to various subtypes of satisfaction to varying degrees. Outpatients who were male, older, married, with low or middle incomes, living in Shanghai or other areas of the People's Republic of China, medical staff, or students were more satisfied with various subtypes of satisfaction than those without these characteristics. In further analyses, satisfaction with their medical needs being met by doctors had the strongest relation to overall satisfaction, followed by satisfaction with doctors' service attitudes, medical costs, waiting time, prescription, and diagnosis and treatment time. Satisfaction with environment had the weakest contribution to overall satisfaction.

Conclusion: This study gave some suggestions for tertiary hospitals in advanced areas of the People's Republic of China. Outpatient sociodemographic characteristics should be paid more attention by medical staff to improve the degree of satisfaction. Tertiary hospitals in the People's Republic of China should provide more support on the management of doctors, medical costs, and time.
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http://dx.doi.org/10.2147/PPA.S104453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844439PMC
May 2016
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