Publications by authors named "Zhi Liang"

137 Publications

Nitrous oxide fluxes from long-term limed soils following P and glucose addition: Nonlinear response to liming rates and interaction from added P.

Sci Total Environ 2021 Jul 16;797:148933. Epub 2021 Jul 16.

Department of Agroecology, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark; iCLIMATE, Aarhus University Interdisciplinary Centre for Climate Change, Blichers Allé 20, 8830 Tjele, Denmark.

Liming of acidic soils to regulate pH for crop growth may decrease emissions of nitrous oxide (NO) due to direct effects of pH on the synthesis of NO reductases by denitrifying bacteria. However, liming also changes general pH-dependent soil properties, including availability of phosphorus (P), with a feedback on NO fluxes that remains largely unknown. Here we used a mesocosm approach to study the combined role of liming and P in regulating NO fluxes from denitrification in an arable coarse sandy soil where NO emissions under field condition coincided with rainfall events and irrigation, which facilitated anoxia. Soils from three long-term liming treatments (0, 4, and 12 Mg ha) with resulting pH(CaCl) of 3.6, 4.7 and 6.3 were incubated at original bulk density first at 60% water filled pore space (WFPS) and successively at 75% WFPS with added nitrate, inorganic P (0 and 10 μg P g soil) and glucose as labile carbon. NO fluxes were measured during 28 days and were supplemented with measurements of CO fluxes, microbial biomass, potential denitrification, and acid phosphatase activity. The results showed a nonlinear response of NO fluxes to liming rates, with highest fluxes at the intermediate liming level (4 Mg ha). Furthermore, inorganic P stimulated NO fluxes only at the intermediate liming level. Assays of potential denitrification indicated that the NO/(NO + N) product ratio decreased consistently with increasing liming rates, but total NO fluxes responded nonlinearly likely due to combined effects on NO/(NO + N) product ratios and total denitrification rates. The results suggest that liming and P addition interact on microbial properties and NO emissions from acidic arable soils and may not follow linear trends. This makes it uncertain to predict and model the resulting net effect, which may depend on the actual pH range and P availability from the unlimed to the limed treatments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148933DOI Listing
July 2021

LXR-Mediated Regulation of Marine-Derived Piericidins Aggravates High-Cholesterol Diet-Induced Cholesterol Metabolism Disorder in Mice.

J Med Chem 2021 Jul 12;64(14):9943-9959. Epub 2021 Jul 12.

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Reported as two antirenal cell carcinoma (RCC) drug candidates, marine-derived compounds piericidin A (PA) and glucopiericidin A (GPA) exhibit hepatotoxicity in renal carcinoma xenograft mice. Proteomics and transcriptomics reveal the hepatotoxicity related with cholesterol disposition since RCC is characterized by cholesterol accumulation. PA/GPA aggravate hepatotoxicity in high-cholesterol diet (HCD)-fed mice while exhibiting no toxicity in chow diet-fed mice. High cholesterol accumulation in liver is liver X receptor (LXR)-mediated cytochrome P450 family 7 subfamily a member 1 (CYP7A1) depression and low-density lipoprotein receptor (LDLR) activation. The farnesoid X nuclear receptor (FXR) is also depressed with a downregulated target gene . Different from PA directly combined with LXRα as an inhibitor, GPA exists as a prodrug in the liver and exerts toxic effects due to transformation into PA. Surface plasmon resonance (SPR) and docking results of 17 piericidins illustrate that glycosides exert no LXRα binding activity. A longer survival time of GPA-treated mice indicates that further exploration in anti-RCC drug research should focus on reducing glycosides transformed into PA and concentrating in the kidney tumor rather than the liver for lowering the risk of hepatotoxicity.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00175DOI Listing
July 2021

Temporal trends in heart failure mortality in an integrated healthcare delivery system, California, and the US, 2001-2017.

BMC Cardiovasc Disord 2021 May 26;21(1):261. Epub 2021 May 26.

Department of Research and Evaluation, Kaiser Permanente Southern California, 100 S Los Robles Ave, 2nd Floor, Pasadena, CA, 91101, USA.

Background: In recent years, decreases in mortality rates attributable to cardiovascular diseases have slowed but mortality attributable to heart failure (HF) has increased.

Methods: Between 2001-2017, trends in age-adjusted mortality with HF as an underlying cause for Kaiser Permanente Southern California (KPSC) members were derived through linkage with state death files and compared with trends among California residents and the US. Average annual percent change (AAPC) and 95% confidence intervals (CI) were calculated using Joinpoint regression. Analyses were repeated examining HF as a contributing cause of death.

Results: In KPSC, the age-adjusted HF mortality rates were comparable to California but lower than the US, increasing from 23.9 per 100,000 person-years (PY) in 2001 to 44.7 per 100,000 PY in 2017, representing an AAPC of 1.3% (95% CI 0.0%, 2.6%). HF mortality also increased in California from 33.9 to 46.5 per 100,000 PY (AAPC 1.5%, 95% CI 0.3%, 2.7%), while remaining unchanged in the US at 57.9 per 100,000 PY in 2001 and 2017 (AAPC 0.0%, 95% CI - 0.5%, 0.5%). Trends among KPSC members ≥ 65 years old were similar to the overall population, while trends among members 45-64 years old were flat between 2001-2017. Small changes in mortality with HF as a contributing cause were observed in KPSC members between 2001 and 2017, which differed from California and the US.

Conclusion: Lower rates of HF mortality were observed in KPSC compared to the US. Given the aging of the US population and increasing prevalence of HF, it will be important to examine individual and care-related factors driving susceptibility to HF mortality.
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http://dx.doi.org/10.1186/s12872-021-02075-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157708PMC
May 2021

Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus.

Bioorg Chem 2021 Jul 20;112:104927. Epub 2021 Apr 20.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, and South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China. Electronic address:

Four new chromene derivatives, pestalotiochromenoic acids A - D (1, 2, 4, and 5), and two new chromone derivatives, pestalotiochromones A and B (6 and 7), were obtained from the marine alga-derived fungus Pestalotiopsis neglecta SCSIO41403, as well as a reported derivate named piperochromenoic acid (3) with its configuration determined for the first time. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic analyses, while the absolute configurations were established by theoretical NMR and electronic circular dichroism (ECD) calculation, including Mo(OAc)-induced ECD experiments. Those chromene and chromone derivatives displayed weak cytotoxicity, but showed obvious liver X receptors (LXRs) modulatory activities, by in vitro tests on the expression of LXRα, LXRβ and theirtarget gene ABCA1, as well as in silico docking analysis. Moreover, the high binding affinities between pestalotiochromone A (6) and LXRα, revealed by surface plasmon resonance (SPR) with the dissociation equilibrium constant (K) value of 6.2 μM, demonstrated 6 could act as a new potential LXR agonist.
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http://dx.doi.org/10.1016/j.bioorg.2021.104927DOI Listing
July 2021

Effects of nonylphenol exposure on histological changes, apoptosis and time-course transcriptome in gills of white shrimp Litopenaeus vannamei.

Sci Total Environ 2021 Aug 25;781:146731. Epub 2021 Mar 25.

College of Fisheries, Guangdong Ocean University, Zhanjiang 524025, China; Guangdong Provincial Key Laboratory of Pathogenic Biology and Epidemiology for Aquatic Economic Animals & Key Laboratory of Control for Diseases of Aquatic Economic Animals of Guangdong Higher Education Institutes, Zhanjiang 524025, China. Electronic address:

Nonylphenol (NP) is considered as one of the persistent organic pollutants (POPs) in the environment. Pacific white shrimp Litopenaeus vannamei is the predominant species in China, which is frequently affected by environmental pollutants. However, potential toxicity mechanism of NP in shrimp has not been comprehensively studied. To explore the physiological changes and molecular mechanism involved in NP exposure of shrimp, we analyzed histological alterations, apoptosis and transcriptional responses of L.vannamei subjected to NP. Results indicated that significant changes in the histoarchitecture of the gills were observed after NP exposure for 3, 12 and 48 h. Apoptosis was also detected in a time-dependent manner. Numerous differentially expressed genes (DEGs) were obtained at 3 h, 12 h and 48 h after exposure. On the basis of the expression patterns over the time course, these DEGs were classified into 12 clusters. GO and KEGG enrichment analysis of these DEGs was carried out and a dynamic and global view was obtained in shrimp after NP exposure on a transcriptome level. In addition, 15 DEGs involved in immune response, apoptosis, DNA repair, osmoregulation etc. were selected for qRT-PCR validation. The expression patterns of these DEGs kept a well consistent with the high-throughput data at different timepoints, which confirmed the accuracy and reliability of the transcriptome data. All the results demonstrated that NP exposure might lead to impairments of biological functions in gills, alter immune and antioxidant response, compromise DNA repair and anti-apoptosis abilities of shrimp, cause severe histopathological changes and eventually trigger apoptosis. The present study enriched the information on the toxicity mechanism of crustaceans in response to NP exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146731DOI Listing
August 2021

Efficacy and safety of ulinastatin on cognitive dysfunction after general anesthesia in elderly patients: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(13):e24814

Department of Anesthesiology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei province, China.

Background: With the aging of society, the incidence of diseases increases. And along with the increase of surgery rate, the number of elderly patients with postoperative cognitive dysfunction (POCD) is also increasing. POCD seriously affects the mental state and quality of life of patients and their families. Clinical studies have shown that POCD is closely related to inflammatory reaction, and Ulinastatin can inhibit the inflammatory reaction and reduce the incidence of POCD in elderly patients under general anesthesia. However. the effect of Ulinastatin on POCD in elderly patients under general anesthesia has not been systematically evaluated.

Objective: Meta analysis will be used to evaluate the efficacy and safety of Ulinastatin in elderly patients with general anesthesia POCD during perioperative period.

Methods: We will search China Science and Technology Journal Database Chinese database, China National Knowledge Infrastructure, Wanfang, China biomedical database, PubMed, EMBASE, Cochrane Library and web of science for randomized controlled trials of the effect of Ulinastatin on POCD of elderly patients with general anesthesia from the establishment of the database to November 2020. The 2 researchers will independently screen the literature and conducted quality assessment and data extraction for the included studies, Revman5.3 software will be used for risk assessment and meta analysis.

Results: In this study, the efficacy and safety of Ulinastatin in elderly patients with general anesthesia POCD will be evaluated by the incidence of postoperative cognitive impairment, mini mental state examination (Mini-Mental State Examination [MMSE]), visual regeneration, associative memory score, S100 β protein, tumor necrosis factor α (TNF- α), interleukin 6 (IL-6), IL- 10 inflammatory factors and the incidence of adverse reactions.

Conclusion: The use of Ulinastatin in perioperative period can significantly reduce the inflammatory level of elderly patients after general anesthesia, effectively prevent the occurrence of POCD and reduce its incidence.

Ethics And Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.

Osf Registration Number: DOI 10.17605/OSF.IO/GY3V7.
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http://dx.doi.org/10.1097/MD.0000000000024814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021364PMC
April 2021

Physarum polycephalum macroplasmodium exhibits countermeasures against TiO nanoparticle toxicity: A physiological, biochemical, transcriptional, and metabolic perspective.

Environ Pollut 2021 Jun 12;279:116936. Epub 2021 Mar 12.

Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, China. Electronic address:

Concerns about the environmental and human health implications of TiO nanoparticles (nTiO) are growing with their increased use in consumer and industrial products. Investigations of the underlying molecular mechanisms of nTiO tolerance in organisms will assist in countering nTiO toxicity. In this study, the countermeasures exhibited by the slime mold Physarum polycephalum macroplasmodium against nTiO toxicity were investigated from a physiological, transcriptional, and metabolic perspective. The results suggested that the countermeasures against nTiO exposure include gene-associated metabolic rearrangements in cellular pathways involved in amino acid, carbohydrate, and nucleic acid metabolism. Gene-associated nonmetabolic rearrangements involve processes such as DNA repair, DNA replication, and the cell cycle, and occur mainly when macroplasmodia are exposed to inhibitory doses of nTiO. Interestingly, the growth of macroplasmodia and mammal cells was significantly restored by supplementation with a combination of responsive metabolites identified by metabolome analysis. Taken together, we report a novel model organism for the study of nTiO tolerance and provide insights into countermeasures taken by macroplasmodia in response to nTiO toxicity. Furthermore, we also present an approach to mitigate the effects of nTiO toxicity in cells by metabolic intervention.
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http://dx.doi.org/10.1016/j.envpol.2021.116936DOI Listing
June 2021

The Application of Community-Based Information from the American Community Survey in a Large Integrated Health Care Organization.

Perm J 2020 12;25:1-3

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA.

Background: The American Community Survey (ACS) is the largest household survey conducted by the US Census Bureau. We sought to describe the community-level characteristics derived from the ACS among enrollees of Kaiser Permanente Southern California (KPSC), evaluate the associations between ACS estimates and selective individual-level health outcomes, and explore how using different scales of the census geography and the linearity assumption affect the associations.

Methods: We examined the associations between track-level and block group-level ACS 5-year estimates and 4 individual-level Healthcare Effectiveness Data and Information Set (HEDIS) outcome measures (comprehensive diabetes care, postpartum care, antidepressant medication management, and childhood immunization status) using multilevel generalized linear models. Odds ratios and their 95% confidence intervals were estimated for every 10% increase in ACS measures.

Results: 6,357,841 addresses were successfully geocoded to at least the tract level. The community-level demographic, socioeconomic, residential, and other ACS measures varied among KPSC health plan enrollees. A majority of these ACS measures were associated with the selected HEDIS health outcomes. The directions of the effects were consistent across health outcomes; however, the magnitudes of the effect sizes varied. Within each HEDIS health outcome, the relative size of the effects appeared to remain similar. Differences between the census tract- and block group-level estimates were minor, especially for measures related to race/ethnicity, education, income, and occupation.

Conclusion: These findings support the use of many ACS measures at neighborhood levels to predict health outcomes. The geographic units might have little effect on the results. The linearity assumption should be made with caution.
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http://dx.doi.org/10.7812/TPP/20.010DOI Listing
December 2020

Regulation of cytochrome P450 4F11 expression by liver X receptor alpha.

Int Immunopharmacol 2021 Jan 10;90:107240. Epub 2020 Dec 10.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Cytochrome P450 4F (CYP4F) enzymes are responsible for the metabolism of eicosanoids, which play important roles in inflammation. Nuclear receptor liver X receptor alpha (LXRα) is a critical signal node connecting inflammation and lipid metabolism. Studies revealed that the release of cytokines and nuclear factor-κB (NF-κB) can change the CYP4F11 expression in HepG2 cells. However, the effect of LXRα on the CYP4F family and the underlying mechanism remain unclear. This study found that CYP4F11 is a target gene of LXRα. Luciferase assays and siRNA transfection showed that LXRα increased the transcription of CYP4F11 and LXRα agonist GW3965 could induce the expression of CYP4F11 by activating the LXRα-CYP4F11 pathway. Besides, overexpression of CYP4F11 could decrease TNF-α and IL-1β in lipopolysaccharide (LPS)-induced THP-1 cells. The finding of the regulation of CYP4F11 may contribute to the anti-inflammatory activity of LXRα agonists.
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http://dx.doi.org/10.1016/j.intimp.2020.107240DOI Listing
January 2021

Long non‑coding RNA ZFPM2‑AS1 promotes colorectal cancer progression by sponging miR‑137 to regulate TRIM24.

Mol Med Rep 2021 02 10;23(2). Epub 2020 Dec 10.

Department of Anorectal Surgery, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.

Accumulating evidence indicates that long non‑coding RNAs (lncRNAs) may serve essential roles during tumorigenesis of colorectal cancer (CRC). The lncRNA ZFPM2‑AS1 was observed to be involved in the progression of numerous types of cancer, such as lung adenocarcinoma and cervical cancer. The aim of the present study was to investigate the expression levels and function of ZFPM2‑AS1 in CRC. Expression levels of ZFPM2‑AS1 in tissue and CRC cells were measured by reverse transcription‑quantitative PCR. Furthermore, cell proliferation and Transwell assays were conducted to investigate the functional role of ZFPM2‑AS1 . In addition, bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation assay and western blotting were performed to explore the possible underlying mechanism. The expression levels of ZFPM2‑AS1 were significantly upregulated in tissue samples from patients with CRC and CRC cell lines compared with normal tissue and normal human colorectal mucosa cell line. Notably, the upregulation of ZFPM2‑AS1 was significantly associated with tumor size, histological differentiation, lymph node metastasis and TNM stage. In addition, ZFPM2‑AS1 knockdown significantly inhibited cell proliferation, migration and invasion compared with the control group . Moreover, it was found that ZFPM2‑AS1 positively regulated tripartite motif containing 24 (TRIM24) expression by sponging miR‑137. In conclusion, the present study indicated that ZFPM2‑AS1 may serve as an oncogene in CRC by regulating the miR‑137/TRIM24 axis.
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http://dx.doi.org/10.3892/mmr.2020.11737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723173PMC
February 2021

iTRAQ and PRM-based comparative proteomic profiling in gills of white shrimp Litopenaeus vannamei under copper stress.

Chemosphere 2021 Jan 7;263:128270. Epub 2020 Sep 7.

Aquatic Species Introduction and Breeding Center of Guangxi Zhuang Autonomous Region, Nanning, 530031, China. Electronic address:

Crustaceans are particularly sensitive to heavy metal pollution. Copper (Cu) is one of typical heavy metal pollutants in aquatic ecosystems. However, limited attention has been paid on the proteomic responses of shrimp under Cu stress. White shrimp Litopenaeus vannamei held in 5‰ seawater were exposed to 5 mg L Cu for 3 h, and the regulatory mechanism in the gills was elucidated using iTRAQ-based quantitative proteomics. The results showed that a total of 5034 proteins were identified, 385 differentially expressed proteins (DEPs), including 147 differentially up-regulated proteins (DUPs) and 238 differentially down-regulated proteins (DDPs) were found. Bioinformatics analysis indicated the DEPs responding to Cu stress mainly involved in cytoskeleton, immune response, stress response, protein synthesis, detoxification, ion homeostasis and apoptosis. Furthermore, we still performed PRM analysis on sarcoplasmic calcium binding protein (SCP), serine proteinase inhibitor B3 (SPIB3), C-type lectin 4 (CTL4), cathepsin L (CATHL), JHE-like carboxylesterase 1 (CXE1) and paramyosin (PMY), and biochemical analysis on Cu/Zn-superoxide dismutase (Cu/Zn-SOD) to validate the iTRAQ results, respectively. The present proteome analysis revealed that Cu stress disrupted the ion homeostasis and protein synthesis, and L.vannamei mainly regulates a series of molecular pathways which contained many key proteins involved in the immune process to protect the organism from Cu stress. Our data provides more insight about the underlying mechanisms that related to the stress response of Cu exposure in crustacean.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128270DOI Listing
January 2021

Maximum evaporating flux of molecular fluids from a planar liquid surface.

Authors:
Eric Bird Zhi Liang

Phys Rev E 2020 Oct;102(4-1):043102

Department of Mechanical Engineering, California State University, Fresno, California 93740, USA.

In this work, we use the kinetic theory of gases (KTG) to develop a theoretical model to understand the role of internal motions of molecules on the maximum evaporation flux from a planar liquid surface. The kinetic theory is applied to study the evaporation of molecular fluids into a vacuum and predict the dimensionless maximum evaporation flux (J_{R,max}, i.e., the ratio of the maximum evaporation flux to the molar flux emitted from a liquid surface). The key assumptions regarding the velocity distribution function (VDF) of polyatomic molecules in the highly nonequilibrium vapor near the evaporating surface are validated by the VDF obtained directly from molecular dynamics (MD) simulations. Our KTG-based analysis shows that J_{R,max} is affected by the specific heat (c_{V,int}) associated with internal degrees of freedom of fluid molecules. When the maximum evaporation flux is reached, the isotropic evaporating vapor far from the liquid surface moves at its speed of sound regardless of whether it is a monatomic vapor or polyatomic vapor. To fundamentally understand the evaporation of a molecular fluid into a vacuum, we solve the Boltzmann transport equation (BTE) to obtain the temperature, density, and flow speed distributions in the highly nonequilibrium evaporating vapor flow. Our BTE solutions indicate that there are several universal features of the evaporating vapor when the maximum evaporation flux occurs. In particular, we find that the evaporating vapor flow speed reaches the maximum value of sqrt[1.5] times the most probable thermal speed in the vapor flow direction at the vacuum boundary, and this maximum value is independent of fluid properties. All theoretical predictions in this work are verified by the MD simulation results of the evaporation of the model liquid Ar and the model liquid n-dodecane into a vacuum, and existing experimental data.
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http://dx.doi.org/10.1103/PhysRevE.102.043102DOI Listing
October 2020

The lncRNA MALAT1/miR-30/Spastin Axis Regulates Hippocampal Neurite Outgrowth.

Front Cell Neurosci 2020 20;14:555747. Epub 2020 Oct 20.

Department of Orthopaedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Spastin, a microtubule-severing enzyme, is important for neurite outgrowth. However, the mechanisms underlying the post-transcriptional regulation of spastin during microtubule-related processes are largely unknown. We demonstrated that the spastin expression level is controlled by a long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-30 (miR-30) axis during neurite outgrowth. The miR-30 expression level decreased in hippocampal neurons with increasing days in culture, and miR-30 overexpression suppressed while miR-30 inhibition promoted neurite outgrowth in hippocampal neurons. Spastin was validated as a target gene of miR-30 using the luciferase reporter assay. The protein expression, microtubule severing activity, and neurite promoting effect of spastin were suppressed by the overexpression of miR-30 mimics and increased by miR-30 inhibitors. MALAT1 expression increased during neurite outgrowth and MALAT1 silencing impaired neurite outgrowth. miR-30 was a sponge target of MALAT1 and MALAT1/miR-30 altered neurite outgrowth in hippocampal neurons. MALAT1 overexpression reversed the inhibitory effect of miR-30 on the activity of a luciferase reporter construct containing spastin, as well as spastin mRNA and protein expression, indicating that spastin was a downstream effector of MALAT1/miR-30. The MALAT1/miR-30 cascade also modulated spastin-induced microtubule severing, and the MALAT1/miR-30/spastin axis regulated neurite outgrowth in hippocampal neurons. This study suggests a new mechanism governing neurite outgrowth in hippocampal neurons involving MALAT1/miR-30-regulated spastin expression.
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http://dx.doi.org/10.3389/fncel.2020.555747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606917PMC
October 2020

Long non‑coding RNA SNHG20 promotes colorectal cancer cell proliferation, migration and invasion via miR‑495/STAT3 axis.

Mol Med Rep 2021 01 12;23(1). Epub 2020 Nov 12.

Department of Anorectal Surgery, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.

Colorectal cancer (CRC) is one of the primary causes of cancer‑associated mortality worldwide. However, the potential molecular mechanism of CRC progression remains unknown. Long non‑coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to be involved in the development and progression of a variety of tumors, including CRC. However, the involvement of SNHG20 in CRC progression remains unclear. The aim of the present study was to investigate the functional role and molecular mechanism of SNHG20 in CRC progression. In the present study, SNHG20 expression was found to be significantly upregulated in CRC tissues and cell lines. Association analysis indicated that high SNHG20 expression was significantly association with greater tumor size (P=0.014), tumor invasion depth (P=0.019), positive lymph node status (P=0.022), distant metastasis (P=0.017) and advanced tumor node metastasis stage (P=0.038). Loss‑of‑function experiments indicated that SNHG20 knockdown could significantly suppress proliferation, migration and invasion . Notably, SNHG20 knockdown significantly inhibited tumor growth and lung metastasis . Bioinformatics analysis and luciferase reporter assays confirmed that microRNA (miR)‑495 was a direct target of SNHG20. Rescue assays indicated that miR‑495 inhibitor reversed the suppressive effects of SNHG20 knockdown on CRC progression. Moreover, STAT3 was identified as a downstream target of miR‑495 in CRC. STAT3 overexpression partially rescued the inhibitory effects of SNHG20 knockdown on CRC progression. Taken together, the results revealed that SNHG20 facilitated CRC progression by regulating STAT3 expression and by sponging miR‑495.
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http://dx.doi.org/10.3892/mmr.2020.11669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705999PMC
January 2021

Expression and antibacterial analysis of galectin-8 and -9 genes in mandarin fish, Siniperca chuatsi.

Fish Shellfish Immunol 2020 Dec 2;107(Pt B):463-468. Epub 2020 Nov 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong Province, 266237, China; School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, Shandong Province, 266109, China. Electronic address:

Galectin-8 and galectin-9 belong to tandem repeat-type galectins, and in the present study, these two genes were cloned in mandarin fish Siniperca chuatsi. The open reading frame (ORF) of the mandarin fish galectin-8 and galectin-9 contains 942, and 1008 bp, encoding 313 and 335 amino acids, respectively. As a conserved feature, an N-terminal carbohydrate recognition domain (CRD), and a C-terminal CRD were observed in each of the two galectins in mandarin fish. In healthy fish, galectin-8 and -9 were constitutively expressed in all organs/tissues examined, and their expression can be induced following the stimulation of LPS and poly(I:C). It is obvious that galectin-8 had a higher increase at mRNA level following the stimulation of poly(I:C). It is further demonstrated that mandarin fish galectin-8 inhibited the growth of Flavobacterium columnare and Streptococcus agalactiae, and in addition to the two species of bacteria, galectin-9 inhibited also the growth of Edwardsiella piscicida, which provides the basis for further understanding their antibacterial role in immune response of mandarin fish.
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http://dx.doi.org/10.1016/j.fsi.2020.10.028DOI Listing
December 2020

Effect of Wrist-Ankle Acupuncture on Propofol Dosage in Painless Gastroscopy of Elderly Patients: A Randomized Controlled Trial.

Am J Ther 2020 Oct 1. Epub 2020 Oct 1.

Department of Acupuncture, Affiliated Hospital of Hebei College of Traditional Chinese Medicine, Shijiazhuang, China.

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http://dx.doi.org/10.1097/MJT.0000000000001272DOI Listing
October 2020

Early, short-term, low-dose glucocorticoid therapy effectively blocks progression of severe acute exacerbation of chronic hepatitis B to liver failure.

Clin Res Hepatol Gastroenterol 2020 Sep 28:101505. Epub 2020 Sep 28.

Deparment of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou City, 510630, PR China. Electronic address:

Objective: To determine whether early, short-term, low-dose glucocorticoid treatment prevents the progression of severe acute exacerbation of chronic hepatitis B to liver failure.

Methods: We prospectively enrolled 125 patients with severe acute exacerbation of chronic hepatitis B from the Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University between September 2013 and March 2016. The patients were randomized to a hormone group (3-day, low-dose glucocorticoid treatment plus conventional treatment; 63 patients) and a control group (conventional treatment only; 62 patients). We analyzed markers of liver function, complications, mortality rates, and duration and cost of hospitalization.

Results: Serum alanine transaminase levels were significantly lower in the hormone group than in the control group at 3 days (P = 0.009) and 1 week (P = 0.018) after treatment. The decrease in this level from the baseline value on day 3 was greater in the hormone group than in the control group (P = 0.023). The trend of the changes in this level significantly differed between the two groups (P = 0.008). The incidence of liver failure (8.06% vs. 30.16%; P = 0.002) and the duration of hospitalization (23.79 vs. 31.79 days; P = 0.031) were significantly lower in the hormone group than in the control group.

Conclusion: Low-dose, short-term glucocorticoid treatment early in the course of severe acute exacerbation of chronic hepatitis B along with conventional treatment significantly reduced the risk of progression to liver failure and shortened the duration of hospitalization, without increasing the complication rate.
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http://dx.doi.org/10.1016/j.clinre.2020.07.010DOI Listing
September 2020

Effects of dezocine, morphine and nalbuphine on electropain threshold, temperature pain threshold and cardiac function in rats with myocardial ischemia.

Ann Palliat Med 2020 Jul;9(4):1556-1563

Department of Anesthesia, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Myocardial ischemia (MI) could cause many complications, such as arrhythmia, ischemic cardiomyopathy, which could lead to angina and myocardial infarction. The clinical efficacy of dezocine, morphine and nalbuphine are becoming dominated in China market. This aim of this study was to investigate the effects of dezocine, morphine and nalbuphine on electrical pain threshold, temperature pain threshold and cardiac function in rats with MI.

Methods: A rat model of MI was established by ligating the coronary artery. Rats in the model group were injected with dezocine, morphine, nalbuphine and 0.9% normal saline. The effects of the three analgesics on MI rats were evaluated by comparing the electrical pain threshold, temperature pain threshold, and cardiac function index.

Results: The electrocardiogram revealed that the model of MI was successful. The results of the electrical pain threshold and temperature pain threshold tests revealed that nalbuphine was the most sensitive after medication, followed by dezocine, and the sensitivity of morphine was the lowest. These three drugs reached its peak at two hours after administration. The analgesic effect of dezocine on electrical stimulation was the best, while nalbuphine had the best effect on temperature. The efficacy of dezocine decreased with time, while morphine basically failed at four hours after administration. The peak time of these three kinds of analgesics was selected to detect the cardiac function index in each group. Morphine had the least influence on the cardiac function index of rats, followed by nalbuphine and dezocine.

Conclusions: These results show that the analgesic effect of nalbuphine had the earliest and best effect with the longest duration on temperature, and had less influence and higher safety in the cardiac function test of MI rats. Hence, nalbuphine is a relatively good analgesic for MI patients. The present study provides a database for the selection of analgesics in patients with MI.
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http://dx.doi.org/10.21037/apm-19-460DOI Listing
July 2020

A transcriptional toolbox for exploring peripheral neuroimmune interactions.

Pain 2020 09;161(9):2089-2106

Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Guy's Campus, London, United Kingdom.

Abstract: Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies, and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type-specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3 1/2 months after the initial injury. This raises the question of whether the commonly used categorisation of pain into "inflammatory" and "neuropathic" is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq data sets on neurons, macrophages, and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data mining of peripheral neuroimmune interactions. http://rna-seq-browser.herokuapp.com/.
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http://dx.doi.org/10.1097/j.pain.0000000000001914DOI Listing
September 2020

Thermal transport across the interface between liquid n-dodecane and its own vapor: A molecular dynamics study.

J Chem Phys 2020 May;152(18):184701

Department of Mechanical Engineering, California State University, Fresno, California 93740, USA.

There are two possible thermal transport mechanisms at liquid-gas interfaces, namely, evaporation/condensation (i.e., heat transfer by liquid-vapor phase change at liquid surfaces) and heat conduction (i.e., heat exchange by collisions between gas molecules and liquid surfaces). Using molecular dynamics (MD) simulations, we study thermal transport across the liquid-vapor interface of a model n-dodecane (CH) under various driving force conditions. In each MD simulation, we restrict the thermal energy to be transferred across the liquid-vapor interface by only one mechanism. In spite of the complex intramolecular interactions in n-dodecane molecules, our modeling results indicate that the Schrage relationships, which were shown to give accurate predictions of evaporation and condensation rates of monatomic fluids, are also valid in the prediction of evaporation and condensation rates of n-dodecane. In the case of heat conduction at the liquid-vapor interface of n-dodecane, the interfacial thermal conductance obtained from MD simulations is consistent with the prediction from the kinetic theory of gases. The fundamental understanding of thermal transport mechanisms at liquid-gas interfaces will allow us to formulate appropriate boundary conditions for continuum modeling of heating and evaporation of small fuel droplets.
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http://dx.doi.org/10.1063/1.5144279DOI Listing
May 2020

Ene-yne Hydroquinones from a Marine-derived Strain of the Fungus with Effects on Liver X Receptor Alpha.

J Nat Prod 2020 04 13;83(4):1258-1264. Epub 2020 Apr 13.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

Seven unusual new ene-yne hydroquinones (-, -), including three rare glycosylated derivatives named pestalotioquinosides A-C (-), were obtained from the marine-derived strain SCSIO41403 of the fungus . Their structures including absolute configurations were elucidated by spectroscopic analysis and induced electronic circular dichroism experiments. In silico molecular docking and surface plasmon resonance studies showed that pestalotioquinoside C () could act as a liver X receptor alpha (LXRα) modulator. Further study showed that LXR target gene was significantly upregulated by , which revealed as a potential LXRα agonist.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00050DOI Listing
April 2020

PlexinA3 Interacts with CRMP2 to Mediate Sema3A Signalling During Dendritic Growth in Cultured Cerebellar Granule Neurons.

Neuroscience 2020 05 14;434:83-92. Epub 2020 Feb 14.

Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address:

Plexin family proteins mediate semaphorin signalling during dendritic arbour development. However, the role of PlexinA3 in the growth of dendrites of cultured cerebellar granule neurons (CGNs) is not known. We found that PlexinA3 colocalizes with CRMP2 (collapsin response mediator protein 2) in dendritic shafts. Immunoprecipitation and glutathione transferase pulldown assays showed that the intracellular Ras-binding domain of PlexinA3 directly interacts with CRMP2. PlexinA3 was necessary and sufficient for the growth of CGN dendrites, as genetic knockdown of PlexinA3 reduced but its overexpression increased dendritic lengths and dendritic tip numbers. These increases were enhanced with CRMP2 overexpression and abolished with CRMP2 knockdown, indicating that CRMP2 is the downstream effector. Furthermore, PlexinA3/CRMP2 signalling contributed to Sema3A-controlled dendritic growth. Together, these data identify a novel PlexinA3/CRMP2 pathway in semaphorin-regulated growth of cultured CGN dendrites.
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http://dx.doi.org/10.1016/j.neuroscience.2020.02.008DOI Listing
May 2020

Soil carbon loss with warming: New evidence from carbon-degrading enzymes.

Glob Chang Biol 2020 Jan 7. Epub 2020 Jan 7.

Department of Agroecology, Aarhus University, Tjele, Denmark.

Climate warming affects soil carbon (C) dynamics, with possible serious consequences for soil C stocks and atmospheric CO concentrations. However, the mechanisms underlying changes in soil C storage are not well understood, hampering long-term predictions of climate C-feedbacks. The activity of the extracellular enzymes ligninase and cellulase can be used to track changes in the predominant C sources of soil microbes and can thus provide mechanistic insights into soil C loss pathways. Here we show, using meta-analysis, that reductions in soil C stocks with warming are associated with increased ratios of ligninase to cellulase activity. Furthermore, whereas long-term (≥5 years) warming reduced the soil recalcitrant C pool by 14%, short-term warming had no significant effect. Together, these results suggest that warming stimulates microbial utilization of recalcitrant C pools, possibly exacerbating long-term climate-C feedbacks.
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http://dx.doi.org/10.1111/gcb.14986DOI Listing
January 2020

A personalized computational model predicts cancer risk level of oral potentially malignant disorders and its web application for promotion of non-invasive screening.

J Oral Pathol Med 2020 May 4;49(5):417-426. Epub 2020 Jan 4.

State Key Laboratory of Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background: Despite their high accuracy to recognize oral potentially malignant disorders (OPMDs) with cancer risk, non-invasive oral assays are poor in discerning whether the risk is high or low. However, it is critical to identify the risk levels, since high-risk patients need active intervention, while low-risk ones simply need to be follow-up. This study aimed at developing a personalized computational model to predict cancer risk level of OPMDs and explore its potential web application in OPMDs screening.

Methods: Each enrolled patient was subjected to the following procedure: personal information collection, non-invasive oral examination, oral tissue biopsy and histopathological analysis, treatment, and follow-up. Patients were randomly divided into a training set (N = 159) and a test set (N = 107). Random forest was used to establish classification models. A baseline model (model-B) and a personalized model (model-P) were created. The former used the non-invasive scores only, while the latter was incremented with appropriate personal features.

Results: We compared the respective performance of cancer risk level prediction by model-B, model-P, and clinical experts. Our data suggested that all three have a similar level of specificity around 90%. In contrast, the sensitivity of model-P is beyond 80% and superior to the other two. The improvement of sensitivity by model-P reduced the misclassification of high-risk patients as low-risk ones. We deployed model-P in web.opmd-risk.com, which can be freely and conveniently accessed.

Conclusion: We have proposed a novel machine-learning model for precise and cost-effective OPMDs screening, which integrates clinical examinations, machine learning, and information technology.
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http://dx.doi.org/10.1111/jop.12983DOI Listing
May 2020

Transport phenomena in the Knudsen layer near an evaporating surface.

Authors:
Eric Bird Zhi Liang

Phys Rev E 2019 Oct;100(4-1):043108

Department of Mechanical Engineering, California State University, Fresno, California 93740, USA.

Using the combination of the kinetic theory of gases (KTG), Boltzmann transport equation (BTE), and molecular dynamics (MD) simulations, we study the transport phenomena in the Knudsen layer near a planar evaporating surface. The MD simulation is first used to validate the assumption regarding the anisotropic velocity distribution of vapor molecules in the Knudsen layer. Based on this assumption, we use the KTG to formulate the temperature and density of vapor at the evaporating surface as a function of the evaporation rate and the mass accommodation coefficient (MAC), and we use these vapor properties as the boundary conditions to find the solution to the BTE for the anisotropic vapor flow in the Knudsen layer. From the study of the evaporation into a vacuum, we show the ratio of the macroscopic speed of vapor to the most probable thermal speed of vapor molecules in the flow direction will always reach the maximum value of sqrt[1.5] at the vacuum boundary. The BTE solutions predict that the maximum evaporation flux from a liquid surface at a given temperature depends on both the MAC and the distance between the evaporating surface and the vacuum boundary. From the study of the evaporation and condensation between two parallel plates, we show the BTE solutions give good predictions of transport phenomena in both the anisotropic vapor flow within the Knudsen layer and the isotropic flow out of the Knudsen layer. All the predictions from the BTE are verified by the MD simulation results.
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http://dx.doi.org/10.1103/PhysRevE.100.043108DOI Listing
October 2019

Iakyricidins A-D, Antiproliferative Piericidin Analogues Bearing a Carbonyl Group or Cyclic Skeleton from SCSIO NS104.

J Org Chem 2019 10 7;84(19):12626-12631. Epub 2019 Aug 7.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica , South China Sea Institute of Oceanology, Chinese Academy of Sciences Guangzhou 510301 , China.

Iakyricidins A-D (-), a carbonyl-containing piericidin derivative and three novel piericidin analogues bearing cyclic skeletons, were isolated from the mangrove sediment derived strain SCSIO NS104. These structures were established by spectroscopic techniques, Mosher's method, and ECD calculations. Compounds - represent a novel skeleton of piericidins with branched chain C-C cyclization, and their biosynthetic pathways are proposed. Compound , the first natural carbonyl-containing piericidin derivate, exhibited potent antiproliferative activity against ACHN with an IC value of 20 nM.
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http://dx.doi.org/10.1021/acs.joc.9b01270DOI Listing
October 2019

Exploring the Natural Piericidins as Anti-Renal Cell Carcinoma Agents Targeting Peroxiredoxin 1.

J Med Chem 2019 08 25;62(15):7058-7069. Epub 2019 Jul 25.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography , University of California at San Diego , La Jolla , California 92093 , United States.

Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty-seven natural products of the piericidin class, including 17 new ones, are obtained from a marine-derived strain, and several of them show strong inhibitory activities against ACHN renal carcinoma cells. By exploring the mechanisms of two representative natural piericidin compounds, piericidin A (PA) and glucopiericidin A (GPA), peroxiredoxin 1 (PRDX1) is detected as a potential target by transcriptome data of PA-treated ACHN cells, as well as the paired RCC tumor versus adjacent nontumor tissues. PA and GPA induce cell apoptosis through reducing the reactive oxygen species level caused by upregulated PRDX1 mRNA and protein level subsequently and exhibit potent antitumor efficacy in nude mice bearing ACHN xenografts, with increasing PRDX1 expression in tumor. The interaction between PA/GPA and PRDX1 was supported by the docking analysis and surface plasmon resonance. Moreover, the translocation of PRDX1 into the nucleus forced by PA/GPA is proposed to be a key factor for the anti-RCC procedure. Piericidins provide a novel scaffold for further development of potent anti-RCC agents, and the new action mechanism of these agents targeting PRDX1 may improve upon the limitations of existing targeted drugs for the treatment of renal cancer.
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http://dx.doi.org/10.1021/acs.jmedchem.9b00598DOI Listing
August 2019

The Efficacy of General Practitioner Assessment of Cognition in Chinese Elders Aged 80 and Older.

Am J Alzheimers Dis Other Demen 2019 Nov-Dec;34(7-8):523-529. Epub 2019 Jul 2.

Wuhan Union Hospital, Neurology Wuhan Union Hospital, Hankou District, Wuhan, Hubei, China.

Objectives: This study examined the efficacy of the General Practitioner Assessment of Cognition-Chinese version (GPCOG-C) in screening dementia and mild cognitive impairment (MCI) among older Chinese.

Methods: Survey questionnaires were administered to 293 participants aged 80 or above from a university hospital in mainland China. Alzheimer disease and MCI were diagnosed in light of the National Institute on Aging and the Alzheimer's Association (NIA/AA) criteria. The sensitivity and specificity of GPCOG-C and Mini-Mental State Examination (MMSE) in screening dementia and MCI were compared to the NIA/AA criteria.

Results: The GPCOG-C had the sensitivity of 62.3% and specificity of 84.6% in screening MCI, which had comparable efficacy as the NIA/AA criteria. In screening dementia, GPCOG-C had a lower sensitivity (63.7%) than the MMSE and a higher specificity (82.6%) higher than the MMSE.

Conclusions: The GPCOG-C is a useful and efficient tool to identify dementia and MCI in older Chinese in outpatient clinical settings.
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http://dx.doi.org/10.1177/1533317519860333DOI Listing
July 2020

MiR-141-3p inhibits cell proliferation, migration and invasion by targeting TRAF5 in colorectal cancer.

Biochem Biophys Res Commun 2019 06 9;514(3):699-705. Epub 2019 May 9.

Department of Anorectal, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China. Electronic address:

Emerging evidence has shown that abnormal microRNA (miRNA) expression play an important role in initiation, progression and metastasis in several tumors, including colorectal cancer. Here, we attempted to explore the expression and function of miR-141-3p in colorectal cancer. MiR-141-3p expression was measured in tissue samples, colorectal cancer cell lines and normal human colon epithelium cell line FHC by real-time PCR. The biological roles of miR-141-3p in colorectal cancer were investigated both in vitro and a mouse model in vivo. Bioinformatics analysis, real-time PCR, Western blot and luciferase reporter analysis were performed to validate the association between miR-141-3p and its potential targets. Our results suggested that miR-141-3p expression was down-regulated in colorectal cancer tissues and colorectal cancer cell lines compared to the normal tissues and normal colon cells. Patients with low miR-141-3p had poor outcome. In addition, Overexpression of miR-141-3p significantly delayed the proliferation, migration, and invasion of colorectal cancer cells in vitro, as well as obviously attenuated tumor growth in a xenograft model in vivo. Furthermore, Our results showed that miR-141-3p inhibited the proliferation, migration, and invasion via directly targeting tumor necrosis factor receptor-associated factor 5 (TRAF5). In summary, miR-141-3p acts as a tumor suppressor, via directly targeting TRAF5 and indicated miR-141-3p might be a potential therapeutic target for colorectal cancer.
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http://dx.doi.org/10.1016/j.bbrc.2019.05.002DOI Listing
June 2019

Temporal Trends in Mortality Rates among Kaiser Permanente Southern California Health Plan Enrollees, 2001-2016.

Perm J 2019 ;23

Kaiser Permanente Southern California Research and Evaluation, Pasadena.

Background: Temporal analyses of death rates in the US have found a decreasing trend in all-cause and major cause-specific mortality rates.

Objectives: To determine mortality trends in Kaiser Permanente Southern California (KPSC), a large insured population, and whether they differ from those of California and the US.

Methods: Trends in age-adjusted all-cause and cause-specific mortality rates from 2001 to 2016 were determined using data collected in KPSC and those derived through linkage with California State death files and were compared with trends in the US and California. Trends of race/ethnicity-specific all-cause and cause-specific mortality rates were also examined. Average annual percent changes (AAPC) and 95% confidence intervals (CI) were calculated.

Results: From 2001 to 2016, the age-adjusted all-cause mortality rate per 100,000 person-years decreased significantly in KPSC (AAPC = -1.84, 95% CI = -2.95 to -0.71), California (AAPC = -1.60, 95% CI = -2.51 to -0.69) and the US (AAPC = -1.10, 95% CI = -1.78 to -0.42). Rates of 2 major causes of death, cancer and heart disease, also decreased significantly in the 3 populations. Differences in trends of age-adjusted all-cause mortality rates and the top 10 cause-specific mortality rates between KPSC and California or the US were not statistically significant at the 95% level. No significant difference was found in the trends of race/ethnicity-specific, sex-specific, or race/ethnicity- and sex-specific all-cause mortality rates between KPSC and California or the US.

Conclusion: Trends in age-adjusted mortality rates in this insured population were comparable to those of the US and California.
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http://dx.doi.org/10.7812/TPP/18-213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499114PMC
February 2020
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