Publications by authors named "Shan Sun"

223 Publications

Facial expression stereotypes of rich and poor adults and children.

Cogn Process 2021 Jun 8. Epub 2021 Jun 8.

School of Psychology, Central China Normal University, Wuhan, China.

Facial expression stereotypes can affect the perception of other people's facial expressions. This study examined facial expression stereotypes of poor and rich adults and children. Experiment 1 found that the adult participants associated rich adults with positive emotions (i.e., happiness) and poor adults with negative emotions (i.e., sadness). In Experiments 2-4, adult participants still thought that rich 4-, 6-, and 10-year-old children would show positive facial expressions (happiness) but did not think that poor 4-, 6-, and 10-year-old children would show negative emotions (sadness). These finding have implications concerning how adults communicate with poor and rich adults and children.
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http://dx.doi.org/10.1007/s10339-021-01040-7DOI Listing
June 2021

Short-Duration Electronic Health Record Option Buttons to Reduce Prolonged Length of Antibiotic Therapy in Outpatients.

Pediatrics 2021 Jun;147(6)

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois;

Background: Prolonged antibiotic therapy may be associated with increased adverse events and antibiotic resistance. We deployed an intervention in the electronic health record (EHR) to reduce antibiotic duration for pediatric outpatients.

Methods: A preintervention and postintervention interrupted time series analysis of antibiotic duration for 7 antibiotics was performed for patients discharged from the ED and clinics of a children's hospital network from 2012 to 2018. In February 2015, clickable 5- and 7-day duration option buttons were deployed in the EHR for clindamycin, cephalexin, ciprofloxacin and levofloxacin, trimethoprim-sulfamethoxazole, amoxicillin, and cefdinir, with an additional 10-day option for the latter 2. Prescribers were able to enter a free-text duration. The option buttons were not announced, and were not linked to a specific diagnosis or quality improvement initiative. The primary outcome was proportion of prescriptions per month with duration of 10 days. Balancing secondary outcomes were reorders of the same agent, return to clinic, and inpatient admissions within 30 days.

Results: There were 54 315 prescriptions for the 7 antibiotics associated with 39 894 patients, 18 683 clinic visits, and 35 632 ED visits. Overall, a -5.1% (95% confidence interval [CI], -8.3% to -2.0%) change in the proportion of prescriptions with a 10-day duration was attributable to the intervention, with larger effects noted for clindamycin (-20.8% [95% CI, -26.9% to -14.7%]) and cephalexin (-9.9% [95% CI, -14.3% to -5.4%]). There was no increase in the reorders of the same agent, return clinical encounters, or inpatient admissions within 30 days.

Conclusions: A simple intervention in the EHR can safely reduce duration of antibiotic therapy.
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http://dx.doi.org/10.1542/peds.2020-034819DOI Listing
June 2021

Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: A GORTEC internationally-reviewed HNCIG-endorsed consensus.

Radiother Oncol 2021 May 11;160:140-147. Epub 2021 May 11.

Department of Radiation Oncology, Hospital Clinic, Barcelona, Spain.

Introduction: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps.

Material And Methods: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance.

Results: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown.

Conclusion: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.
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http://dx.doi.org/10.1016/j.radonc.2021.04.026DOI Listing
May 2021

Identification and Characterization of EvpQ, a Novel T6SS Effector Encoded on a Mobile Genetic Element in .

Front Microbiol 2021 11;12:643498. Epub 2021 Mar 11.

State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

In this study, a hypothetical protein (ORF02740) secreted by was identified. We renamed the ORF02740 protein as EvpQ, which is encoded by a mobile genetic element (MGE) in genome. The gene is spaced by 513 genes from type VI secretion system (T6SS) gene cluster. Low GC content, three tRNA, and three transposase genes nearby define this MGE that localizes as a genomic island. Sequence analysis reveals that EvpQ shares a conserved domain of C70 family cysteine protease and shares 23.91% identity with T3SS effector AvrRpt2 of phytopathogenic Instead, EvpQ of is proved to be secreted at a T6SS-dependent manner, and it can be translocated into host cells. EvpQ is thereof a novel T6SS effector. Significantly decreased competitive index of Δ strain in blue gourami fish (0.53 ± 0.27 in head kidney and 0.44 ± 0.19 in spleen) indicates that EvpQ contributes to the pathogenesis of . At 8-, 18-, and 24-h post-subculture into DMEM, the transcription of was found to be negatively regulated by Fur and positively regulated by EsrC, and the steady-state protein levels of EvpQ are negatively controlled by RpoS. Our study lays a foundation for further understanding the pathogenic role of T6SS in edwardsiellosis.
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http://dx.doi.org/10.3389/fmicb.2021.643498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991086PMC
March 2021

Lack of association of the esophageal microbiome in adults with eosinophilic esophagitis compared with non-EoE controls.

J Gastrointestin Liver Dis 2021 Mar 12;30(1):17-24. Epub 2021 Mar 12.

Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Background And Aims: Changes in the esophageal microbiome have been reported in children with eosinophilic esophagitis (EoE), but few data exist for adults. We aimed to determine whether the esophageal microbiome differs in adults with and without EoE.

Methods: In a prospective cohort study, adults undergoing outpatient endoscopy were enrolled as incident EoE cases or non-EoE controls. Clinical, endoscopic, and histologic data were collected. An esophageal biopsy was utilized for microbiome analysis. Bacterial DNA was extracted and the V3-V4 region of the 16S rRNA gene was amplified and sequenced. Analyses were performed comparing microbiome features for cases and controls, and within cases for disease features, with correction for multiple hypothesis testing.

Results: A total of 24 incident EoE cases (mean age 40 years; 63% male; 100% white; 97 eos/hpf) and 25 controls (mean age 48, 36% male; 76% white; 1 eos/hpf) were analyzed. Principal coordinate analysis ordination failed to distinguish cases from controls. There were no microbiome differences within EoE cases based on clinical phenotype, presence of atopy, or endoscopic features. Use of proton pump inhibitors (PPIs), however, was significantly associated with 5 taxa including SR1 at the phylum level and Burkholderia at the genus level.

Conclusions: There were no significant differences in the esophageal microbiome between newly diagnosed EoE cases and non-EoE controls in adults, or within EoE cases based on clinical features. However, given the strong rationale for the esophageal microbiome in EoE pathogenesis, future studies should explicitly consider the presence of PPIs as a confounding feature.
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http://dx.doi.org/10.15403/jgld-3049DOI Listing
March 2021

The Rice Small Auxin-Up RNA Gene Regulates Seed Vigor via Sugar Pathway during Early Seed Germination.

Int J Mol Sci 2021 Feb 4;22(4). Epub 2021 Feb 4.

The Laboratory of Seed Science and Technology, Guangdong Key Laboratory of Plant Molecular Breeding, Guangdong Laboratory of Lingnan Modern Agriculture, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China.

Seed vigor affects seed germination and seedling emergence, and therefore is an important agronomic trait in rice. Small auxin-up RNAs () function in a range of developmental processes, but their role in seed vigor remains unclear. Here, we observed that disruption of resulted in reduced germination rates and low seed uniformity in early germination. Expression of was higher in mature grains and early germinating seeds. RNA-seq analysis revealed that modulated seed vigor by affecting the mobilization of stored reserves during germination. Disruption of increased the soluble sugar content in dry mature grains and seeds during early germination. OsSAUR33 interacted with the sucrose non-fermenting-1-related protein kinase OsSnRK1A, a regulator of the sugar signaling pathway, which influences the expression of sugar signaling-related genes during germination. Disruption of increased sugar-sensitive phenotypes in early germination, suggesting OsSAUR33 likely affects seed vigor through the sugar pathway. One elite haplotype of associated with higher seed vigor was identified mainly in accessions. This study provides insight into the effects of OsSAUR33 on seed vigor in rice.
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http://dx.doi.org/10.3390/ijms22041562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913900PMC
February 2021

Whole Cell Active Inhibitors of Mycobacterial Lipoamide Dehydrogenase Afford Selectivity over the Human Enzyme through Tight Binding Interactions.

ACS Infect Dis 2021 02 2;7(2):435-444. Epub 2021 Feb 2.

Tri-Institutional Therapeutics Discovery Institute, New York, New York 10065, United States.

Tuberculosis remains a leading cause of death from a single bacterial infection worldwide. Efforts to develop new treatment options call for expansion into an unexplored target space to expand the drug pipeline and bypass resistance to current antibiotics. Lipoamide dehydrogenase is a metabolic and antioxidant enzyme critical for mycobacterial growth and survival in mice. Sulfonamide analogs were previously identified as potent and selective inhibitors of mycobacterial lipoamide dehydrogenase but lacked activity against whole mycobacteria. Here we present the development of analogs with improved permeability, potency, and selectivity, which inhibit the growth of in axenic culture on carbohydrates and within mouse primary macrophages. They increase intrabacterial pyruvate levels, supporting their on-target activity within mycobacteria. Distinct modalities of binding between the mycobacterial and human enzymes contribute to improved potency and hence selectivity through induced-fit tight binding interactions within the mycobacterial but not human enzyme, as indicated by kinetic analysis and crystallography.
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http://dx.doi.org/10.1021/acsinfecdis.0c00788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888283PMC
February 2021

Effect of pre-frying on distribution of protons and physicochemical qualities of mackerel.

J Sci Food Agric 2021 Jan 31. Epub 2021 Jan 31.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.

Background: In this work, low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging were used to investigate the changes in protons (from water and oil) distribution of mackerel during the frying process. The relationship between proton migration and some physicochemical indexes was established by partial least squares regression (PLSR). The changing mechanism of the quality characteristics and physicochemical properties of fish meat under different frying conditions was analysed by LF-NMR combined with PLSR, which provided theoretical support for the development of canned mackerel food.

Results: LF-NMR results showed that three kinds of T protons assigned to protein-water interaction (T ), multilayer bound water (T ), oil and free water (T ), respectively. As the frying temperature increased, protons from the T peak significantly decreased, while protons from the T peak remarkably increased. The microstructure of fried mackerel was destroyed; cooking loss, oil content, a* value, b* value, hardness and chewiness increased; and the protein content and L* value decreased. Furthermore, PLSR analysis revealed that significant correlation was observed between the cooking loss, TPA parameter (chewiness), colour parameter (L*) and LF-NMR parameters.

Conclusion: Different frying temperatures and times had a strong effect on the physicochemical properties of mackerel. Good prediction models could be established by proton migration using the LF-NMR technique and PLSR for fried mackerel. Quality control of fried fish could be realized by monitoring the change in LF-NMR data. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11130DOI Listing
January 2021

Prevalence and Characteristics of Non-Beta-Lactam Allergy Labeling at a Children's Hospital.

J Pediatric Infect Dis Soc 2021 May;10(5):702

Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.

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http://dx.doi.org/10.1093/jpids/piaa171DOI Listing
May 2021

Laryngopharyngeal Reflux and Inflammatory Responses in Mucosal Barrier Dysfunction of the Upper Aerodigestive Tract.

J Inflamm Res 2020 5;13:1291-1304. Epub 2021 Jan 5.

Otorhinolaryngology Department, ENT Institute, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200032, People's Republic of China.

The upper aerodigestive tract (UAT) is the first line of defense against environmental stresses such as antigens, microbes, inhalants, foods, etc., and mucins, intracellular junctions, epithelial cells, and immune cells are the major constituents of this defensive mucosal barrier. Laryngopharyngeal reflux (LPR) is recognized as an independent risk factor for UAT mucosal disorders, and in this review, we describe the components and functions of the mucosal barrier and the results of LPR-induced mucosal inflammation in the UAT. We discuss the interactions between the refluxate and the mucosal components and the mechanisms through which these damaging events disrupt and alter the mucosal barriers. In addition, we discuss the dynamic alterations in the mucosal barrier that might be potential therapeutic targets for LPR-induced disorders.
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http://dx.doi.org/10.2147/JIR.S282809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801919PMC
January 2021

Does geographical variation confound the relationship between host factors and the human gut microbiota: a population-based study in China.

BMJ Open 2020 11 19;10(11):e038163. Epub 2020 Nov 19.

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, Beijing, China.

Objective: The human gut microbiota plays important roles in human health but is also known to be highly diverse between populations from different regions. Yet most studies inadequately account for this regional diversity in their analyses. This study examines the extent to which geographical variation can act as a confounding variable for studies that associate the microbiota with human phenotypic variation.

Design: Population-based study.

Setting: China.

Participants: 2164 participants from 15 province-level divisions in China.

Primary And Secondary Outcome Measures: We analysed the impact of geographic location on associations between the human gut microbiota and 72 host factors representing a wide variety of environmental-level, household-level and individual-level factors.

Results: While the gut microbiota varied across a wide range of host factors including urbanisation, occupation and dietary variables, the geographic region (province/megacity) of the participants explained the largest proportion of the variance (17.9%). The estimated effect sizes for other host factors varied substantially by region with little evidence of a reproducible signal across different areas as measured by permutational multivariate analysis of variance and random forest models.

Conclusions: Our results suggest that geographic variation is an essential factor that should be explicitly considered when generalising microbiota-based models to host phenotype across different populations.
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http://dx.doi.org/10.1136/bmjopen-2020-038163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678355PMC
November 2020

Hsp90 inhibitor-loaded IR780 micelles for mitochondria-targeted mild-temperature photothermal therapy in xenograft models of human breast cancer.

Cancer Lett 2021 Mar 23;500:41-50. Epub 2020 Dec 23.

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, PR China. Electronic address:

Mitochondria-targeted mild-temperature photothermal therapy (MT-PTT) is a promising strategy that can maximize anticancer effects and reduce adverse reactions. Here, a novel photosensitizer with mitochondrial targeting based on IR780 iodide and heat shock protein 90 inhibitor (BIIB021), which can passively accumulate in MCF-7 cells and achieve effective MT-PTT effect is synthesized. The prepared PEG-IR780-BIIB021 nano-micelles possess considerable biocompatibility and biological stability, with an encapsulation efficiency of about 84% for BIIB021. They can selectively enrich in mitochondria, and release BIIB021 after NIR irradiation to reduce cell tolerance to heat, thereby reducing the mitochondrial membrane potential and rapidly affecting key intrinsic apoptotic factors (Cyt-C, Caspase-9, Bcl-2 and Bax) to achieve the effect of MT-PTT. It is believed that mitochondria-targeted MT-PTT generated by the PEG-IR780-BIIB021 nano-micelles is a promising therapeutic strategy in clinical practice.
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http://dx.doi.org/10.1016/j.canlet.2020.12.028DOI Listing
March 2021

Gut Microbiota and Host Plasma Metabolites in Association with Blood Pressure in Chinese Adults.

Hypertension 2021 Feb 21;77(2):706-717. Epub 2020 Dec 21.

From the Department of Nutrition (Y.W., M.C.B.T., K.A.M., P.G.-L.), University of North Carolina at Chapel Hill (UNC-Chapel Hill).

Animal studies have revealed gut microbial and metabolic pathways of blood pressure (BP) regulation, yet few epidemiological studies have collected microbiota and metabolomics data in the same individuals. In a population-based, Chinese cohort who did not report antihypertension medication use (30-69 years, 54% women), thus minimizing BP treatment effects, we examined multivariable-adjusted (eg, diet, physical activity, smoking, kidney function), cross-sectional associations between measures of gut microbiota (16S rRNA [ribosomal ribonucleic acid], N=1003), and plasma metabolome (liquid chromatography-mass spectrometry, N=434) with systolic (SBP, mean [SD]=126.0 [17.4] mm Hg) and diastolic BP (DBP [80.7 (10.7) mm Hg]). We found that the overall microbial community assessed by principal coordinate analysis varied by SBP and DBP (permutational multivariate ANOVA <0.05). To account for strong correlations across metabolites, we first examined metabolite patterns derived from principal component analysis and found that a lipid pattern was positively associated with SBP (linear regression coefficient [95% CI] per 1 SD pattern score: 2.23 [0.72-3.74] mm Hg) and DBP (1.72 [0.81-2.63] mm Hg). Among 1104 individual metabolites, 34 and 39 metabolites were positively associated with SBP and DBP (false discovery rate-adjusted linear model <0.05), respectively, including linoleate, palmitate, dihomolinolenate, 8 sphingomyelins, 4 acyl-carnitines, and 2 phosphatidylinositols. Subsequent pathway analysis showed that metabolic pathways of long-chain saturated acylcarnitine, phosphatidylinositol, and sphingomyelins were associated with SBP and DBP (false discovery rate-adjusted Fisher exact test <0.05). Our results suggest potential roles of microbiota and metabolites in BP regulation to be followed up in prospective and clinical studies.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856046PMC
February 2021

Effect of nicorandil treatment adjunctive to percutaneous coronary intervention in patients with acute myocardial infarction: a systematic review and meta-analysis.

J Int Med Res 2020 Nov;48(11):300060520967856

Department of Cardiology, Tianjin Chest Hospital, Tianjin, China.

Objective: There is controversy whether nicorandil treatment has cardioprotective effects in patients with acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). This meta-analysis was conducted to assess the efficacy of nicorandil on functional and clinical outcomes after PCI.

Methods: Systematic databases were searched to retrieve studies that compared the effect of nicorandil with a control group in patients with AMI who underwent PCI. Outcomes related to coronary blood flow, and functional and clinical outcomes were extracted and a meta-analysis was performed. Trial sequential analysis was conducted to estimate the required sample size for statistical power.

Results: Twenty-four trials involving 2965 patients with AMI were enrolled. Pooled results showed that nicorandil treatment significantly suppressed the incidence of no-reflow phenomenon and reperfusion arrhythmia after reperfusion, improved the left ventricular ejection fraction and left ventricular end-systolic volume index, and reduced major adverse cardiovascular events and cardiovascular death. Trial sequential analysis confirmed the effect of nicorandil in reducing the incidence of no-reflow phenomenon and follow-up major adverse cardiovascular events in patients with AMI after PCI.

Conclusion: Our findings suggest that nicorandil treatment adjunctive to reperfusion therapy improves myocardial reperfusion, cardiac function, and clinical outcomes in patients with AMI.
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http://dx.doi.org/10.1177/0300060520967856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708727PMC
November 2020

A genome-wide association study reveals that the glucosyltransferase OsIAGLU regulates root growth in rice.

J Exp Bot 2021 02;72(4):1119-1134

The Laboratory of Seed Science and Technology, Guangdong Key Laboratory of Plant Molecular Breeding, Guangdong Laboratory of Lingnan Modern Agriculture, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, People's Republic of China.

Good root growth in the early post-germination stages is an important trait for direct seeding in rice, but its genetic control is poorly understood. In this study, we examined the genetic architecture of variation in primary root length using a diverse panel of 178 accessions. Four QTLs for root length (qRL3, qRL6, qRL7, and qRL11) were identified using genome-wide association studies. One candidate gene was validated for the major QTL qRL11, namely the glucosyltransferase OsIAGLU. Disruption of this gene in Osiaglu mutants reduced the primary root length and the numbers of lateral and crown roots. The natural allelic variations of OsIAGLU contributing to root growth were identified. Functional analysis revealed that OsIAGLU regulates root growth mainly via modulating multiple hormones in the roots, including levels of auxin, jasmonic acid, abscisic acid, and cytokinin. OsIAGLU also influences the expression of multiple hormone-related genes associated with root growth. The regulation of root growth through multiple hormone pathways by OsIAGLU makes it a potential target for future rice breeding for crop improvement.
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http://dx.doi.org/10.1093/jxb/eraa512DOI Listing
February 2021

alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade.

Proc Natl Acad Sci U S A 2020 11 19;117(44):27509-27515. Epub 2020 Oct 19.

Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China;

Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-dependent manner. Moreover, this altered commensal community enhanced both the mitochondrial fitness and the IL-10-mediated suppressive functions of intestinal Tregs, contributing to the amelioration of colitis during immune checkpoint blockade.
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http://dx.doi.org/10.1073/pnas.1921223117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959554PMC
November 2020

Associations of sodium and potassium consumption with the gut microbiota and host metabolites in a population-based study in Chinese adults.

Am J Clin Nutr 2020 12;112(6):1599-1612

Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill (UNC-Chapel Hill), Chapel Hill, NC, USA.

Background: There is increasing evidence that sodium consumption alters the gut microbiota and host metabolome in murine models and small studies in humans. However, there is a lack of population-based studies that capture large variations in sodium consumption as well as potassium consumption.

Objective: We examined the associations of energy-adjusted dietary sodium (milligrams/kilocalorie), potassium, and sodium-to-potassium (Na/K) ratio with the microbiota and plasma metabolome in a well-characterized Chinese cohort with habitual excessive sodium and deficient potassium consumption.

Methods: We estimated dietary intakes from 3 consecutive validated 24-h recalls and household inventories. In 2833 adults (18-80 y old, 51.2% females), we analyzed microbial (genus-level 16S ribosomal RNA) between-person diversity, using distance-based redundancy analysis (dbRDA), and within-person diversity and taxa abundance using linear regression, accounting for geographic variation in both. In a subsample (n = 392), we analyzed the overall metabolome (dbRDA) and individual metabolites (linear regression). P values for specific taxa and metabolites were false discovery rate adjusted (q-value).

Results: Sodium, potassium, and Na/K ratio were associated with microbial between-person diversity (dbRDA P < 0.01) and several specific taxa with large geographic variation, including pathogenic Staphylococcus and Moraxellaceae, and SCFA-producing Phascolarctobacterium and Lachnospiraceae (q-value < 0.05). For example, sodium and Na/K ratio were positively associated with Staphylococcus and Moraxellaceae in Liaoning, whereas potassium was positively associated with 2 genera from Lachnospiraceae in Shanghai. Additionally, sodium, potassium, and Na/K ratio were associated with the overall metabolome (dbRDA P ≤ 0.01) and several individual metabolites, including butyrate/isobutyrate and gut-derived phenolics such as 1,2,3-benzenetriol sulfate, which was negatively associated with sodium in Guizhou (q-value < 0.05).

Conclusions: Our findings suggest that sodium and potassium consumption is associated with taxa and metabolites that have been implicated in cardiometabolic health, providing insights into the potential roles of gut microbiota and host metabolites in the pathogenesis of sodium- and potassium-associated diseases. More studies are needed to confirm our results.
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http://dx.doi.org/10.1093/ajcn/nqaa263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727480PMC
December 2020

GISS-E2.1: Configurations and Climatology.

J Adv Model Earth Syst 2020 Aug 11;12(8):e2019MS002025. Epub 2020 Aug 11.

NASA Goddard Institute for Space Studies New York NY USA.

This paper describes the GISS-E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS-E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden-Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2 × CO is slightly higher than previously at 2.7-3.1°C (depending on version) and is a result of lower CO radiative forcing and stronger positive feedbacks.
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http://dx.doi.org/10.1029/2019MS002025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507764PMC
August 2020

The state of the art of sound therapy for subjective tinnitus in adults.

Ther Adv Chronic Dis 2020 14;11:2040622320956426. Epub 2020 Sep 14.

ENT Institute and Otorhinolaryngology Department of Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, 83 Fenyang Road, Shanghai 200031, China.

Background: Sound therapy is a clinically common method of tinnitus management. Various forms of sound therapy have been developed, but there are controversies regarding the selection criteria and the efficacy of different forms of sound therapy in the clinic. Our goal was to review the types and forms of sound therapy and our understanding of how the different characteristics of tinnitus patients influence their curative effects so as to provide a reference for personalized choice of tinnitus sound therapy.

Method: Using an established methodological framework, a search of six databases including PubMed identified 43 records that met our inclusion criteria. The search strategy used the following key words: tinnitus AND (acoustic OR sound OR music) AND (treatment OR therapy OR management OR intervention OR measure).

Results: There are various forms of sound therapy, and most of them show positive therapeutic effects. The effect of customized sound therapy is generally better than that of non-customized sound therapy, and patients with more severe initial tinnitus respond better to sound therapy.

Conclusion: Sound therapy can effectively suppress tinnitus, at least in some patients. However, there is a lack of randomized controlled trials to identify effective management strategies. Further studies are needed to identify the most effective form of sound therapy for individualized therapy, and large, multicenter, long-term follow-up studies are still needed in order to develop more effective and targeted sound-therapy protocols. In addition, it is necessary to analyze the characteristics of individual tinnitus patients and to unify the assessment criteria of tinnitus.
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http://dx.doi.org/10.1177/2040622320956426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493236PMC
September 2020

A mathematical model of kin selection in floral displays.

J Theor Biol 2021 01 20;509:110470. Epub 2020 Sep 20.

Department of Mathematics and Applied Mathematics, Virginia Commonwealth University, Richmond, VA 23284-2014, USA. Electronic address:

Plants can adjust their competitive traits for acquiring resources in response to the relatedness of their neighbours. Recently, it has been found that plants can alter their investment in traits of attracting pollinators based on kin-interaction. We build a mathematical model to study the optimal floral display to attract pollinators in a patch with kin structure. We show that when plants can attract pollinators to a whole patch through the magnet effect, the floral display should increase with the increasing relatedness of the plants in the patch. Our model also indicates that increasing investment into attracting pollinators is a form of altruism, reducing a plant's own seed production but increasing the contribution of other plants to its fitness. We also predict that seed production should increase with increasing relatedness in the patch. Our model provides the explicit conditions when resource allocation to attract pollinators in response to neighbour relatedness can be favoured by kin selection, and a possible mechanism for the plants to deal with the consequent loss of pollinator diversity and abundance.
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http://dx.doi.org/10.1016/j.jtbi.2020.110470DOI Listing
January 2021

Tumor Microenvironment Stimuli-Responsive Fluorescence Imaging and Synergistic Cancer Therapy by Carbon-Dot-Cu Nanoassemblies.

Angew Chem Int Ed Engl 2020 11 11;59(47):21041-21048. Epub 2020 Sep 11.

Cixi Institute of Biomedical Engineering, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, 1219 ZhongGuan West Road, Ningbo, 315201, China.

A method is developed to fabricate tumor microenvironment (TME) stimuli-responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs-Ce6) and Cu . The as-obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs-Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Introducing of Cu not only provides extra chemodynamic therapy (CDT) function through reaction with hydrogen peroxide (H O ), but also depletes GSH in tumors by a redox reaction, thus amplifying the intracellular oxidative stress and enhancing the efficacy of reactive oxygen species (ROS) based therapy. Cu/CC NPs can act as a FL imaging guided trimodal synergistic cancer treatment agent by photothermal therapy (PTT), PDT, and thermally amplified CDT.
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http://dx.doi.org/10.1002/anie.202007786DOI Listing
November 2020

Inhibition of IRF5 hyperactivation protects from lupus onset and severity.

J Clin Invest 2020 12;130(12):6700-6717

Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, Feinstein Institutes for Medical Research, Manhasset, New York, USA.

The transcription factor IFN regulatory factor 5 (IRF5) is a central mediator of innate and adaptive immunity. Genetic variations within IRF5 are associated with a risk of systemic lupus erythematosus (SLE), and mice lacking Irf5 are protected from lupus onset and severity, but how IRF5 functions in the context of SLE disease progression remains unclear. Using the NZB/W F1 model of murine lupus, we show that murine IRF5 becomes hyperactivated before clinical onset. In patients with SLE, IRF5 hyperactivation correlated with dsDNA titers. To test whether IRF5 hyperactivation is a targetable function, we developed inhibitors that are cell permeable, nontoxic, and selectively bind to the inactive IRF5 monomer. Preclinical treatment of NZB/W F1 mice with an inhibitor attenuated lupus pathology by reducing serum antinuclear autoantibodies, dsDNA titers, and the number of circulating plasma cells, which alleviated kidney pathology and improved survival. Clinical treatment of MRL/lpr and pristane-induced lupus mice with an inhibitor led to significant reductions in dsDNA levels and improved survival. In ex vivo human studies, the inhibitor blocked SLE serum-induced IRF5 activation and reversed basal IRF5 hyperactivation in SLE immune cells. We believe this study provides the first in vivo clinical support for treating patients with SLE with an IRF5 inhibitor.
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http://dx.doi.org/10.1172/JCI120288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685739PMC
December 2020

A colorimetric sensor array for the discrimination of Chinese liquors.

Analyst 2020 Oct;145(21):6968-6973

Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering (NIMTE), Chinese Academy of Sciences, Ningbo 315201, China.

Although some colorimetric sensor arrays have been developed for the identification of Chinese liquors, they usually require the confirmation of volatile markers in the liquors by chromatography and mass spectrometry firstly. Herein, we present a simple colorimetric sensor array to identify various Chinese liquors in the liquid phase without the aid of other analytical techniques. The colorimetric sensor array consists of six commercially available and inexpensive solvatochromic dyes, and the sensing mechanism of this array is based on the response of solvatochromic dyes to their local polarity. On the basis of the colour changes of the sensor array, different Chinese liquors are discerned readily using pattern recognition methods, and the statistical analysis results (i.e., hierarchical clustering analysis and principal component analysis) reveal that the as-fabricated sensor array can distinguish the subtle differences between different liquors from the same winery and the same flavor type. Moreover, the developed sensor array can even distinguish diverse diluted liquors from the pristine ones.
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http://dx.doi.org/10.1039/d0an01496fDOI Listing
October 2020

Circulating Short-Chain Fatty Acids Are Positively Associated with Adiposity Measures in Chinese Adults.

Nutrients 2020 Jul 17;12(7). Epub 2020 Jul 17.

Department of Nutrition, Gillings School of Global Public Health & School of Medicine, University of North Carolina at Chapel Hill (UNC-Chapel Hill), Chapel Hill, NC 27599, USA.

Epidemiological studies suggest a positive association between obesity and fecal short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary carbohydrates, while animal models suggest increased energy harvest through colonic SCFA production in obesity. However, there is a lack of human population-based studies with dietary intake data, plasma SCFAs, gut microbial, and anthropometric data. In 490 Chinese adults aged 30-68 years, we examined the associations between key plasma SCFAs (butyrate/isobutyrate, isovalerate, and valerate measured by non-targeted plasma metabolomics) with body mass index (BMI) using multivariable-adjusted linear regression. We then assessed whether overweight (BMI ≥ 24 kg/m) modified the association between dietary-precursors of SCFAs (insoluble fiber, total carbohydrates, and high-fiber foods) with plasma SCFAs. In a sub-sample ( = 209) with gut metagenome data, we examined the association between gut microbial SCFA-producers with BMI. We found positive associations between butyrate/isobutyrate and BMI (-value < 0.05). The associations between insoluble fiber and butyrate/isobutyrate differed by overweight (-value < 0.10). There was no statistical evidence for an association between microbial SCFA-producers and BMI. In sum, plasma SCFAs were positively associated with BMI and that the colonic fermentation of fiber may differ for adults with versus without overweight.
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http://dx.doi.org/10.3390/nu12072127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400849PMC
July 2020

Auditory Neural Plasticity in Tinnitus Mechanisms and Management.

Neural Plast 2020 1;2020:7438461. Epub 2020 Jul 1.

ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China.

Tinnitus, which is the perception of sound in the absence of a corresponding external acoustic stimulus, including change of hearing and neural plasticity, has become an increasingly important ailment affecting the daily life of a considerable proportion of the population and causing significant burdens for both the affected individuals and society as a whole. Here, we briefly review the epidemiology and classification of tinnitus, and the currently available treatments are discussed in terms of the available evidence for their mechanisms and efficacy. The conclusion drawn from the available evidence is that there is no specific medication for tinnitus treatment at present, and tinnitus management might provide better solutions. Therapeutic interventions for tinnitus should be based on a comprehensive understanding of the etiology and features of individual cases of tinnitus, and more high quality and large-scale research studies are urgently needed to develop more efficacious medications.
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http://dx.doi.org/10.1155/2020/7438461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349625PMC
July 2020

Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice.

Cell Prolif 2020 Sep 17;53(9):e12872. Epub 2020 Jul 17.

Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.

Objectives: To investigate the role of dibenzazepine (DBZ) in promoting supporting cell (SC) proliferation and hair cell (HC) regeneration in the inner ear.

Materials And Methods: Postnatal day 1 wild-type or neomycin-damaged mouse cochleae were cultured with DBZ. Immunohistochemistry and scanning electron microscopy were used to examine the morphology of cochlear cells, and high-throughput RNA-sequencing was used to measure gene expression levels.

Results: We found that DBZ promoted SC proliferation and HC regeneration in a dose-dependent manner in both normal and damaged cochleae. In addition, most of the newly regenerated HCs induced by DBZ had visible and relatively mature stereocilia bundle structures. Finally, RNA sequencing detected the differentially expressed genes between DBZ treatment and controls, and interaction networks were constructed for the most highly differentially expressed genes.

Conclusions: Our study demonstrates that DBZ can significantly promote SC proliferation and increase the number of mitotically regenerated HCs with relatively mature stereocilia bundles in the neonatal mouse cochlea by inhibiting Notch signalling and activating Wnt signalling, suggesting the DBZ might be a new therapeutic target for stimulating HC regeneration.
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http://dx.doi.org/10.1111/cpr.12872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507434PMC
September 2020

Documentation of Indications: Agreement Between Order Entry and Clinical Notes and Effect on Time to Antibiotic Administration.

J Pharm Pract 2020 Jul 9:897190020938225. Epub 2020 Jul 9.

Ann & Robert H. Lurie Children's Hospital of Chicago, IL, USA.

Background/objectives: Antibiotic indication documentation at the time of order entry is mandated by the Joint Commission. Inclusion of indication at order entry may have an impact on the time to administration. Our primary objective was to evaluate agreement between indication selected during order entry and clinical notes. Our secondary objective was to observe if there was a change in time to administration after indications were required during order entry.

Methods: Patients ≤18 years old who received ≥1 dose of vancomycin or ceftriaxone during a preintervention period and 3 postintervention periods were included. Indication for use, agreement between order and clinical note, and timing of antibiotic administration were collected.

Results: Most common indication for vancomycin (total: 789) was sepsis (26%, n = 204). Common indications for ceftriaxone (total: 1071) were sepsis (12%, n = 127), perforated appendicitis (12%, n = 125), and urinary tract infection (10%, n = 107). Postintervention, agreement between the indication selected during order entry and indication documented in clinical note for ceftriaxone and vancomycin orders were 41% and 46%, respectively. Median time to administration decreased among patients who received ceftriaxone ( < .01) but had no significant impact on time to administration of vancomycin ( = .49).

Conclusions: Indication for ceftriaxone and vancomycin selected during order entry and reported in clinical notes inconsistently matched. Inclusion of antibiotic indication may impact time to administration.
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http://dx.doi.org/10.1177/0897190020938225DOI Listing
July 2020

A Missense Mutation in IRS1 is Associated with the Development of Early-Onset Type 2 Diabetes.

Int J Endocrinol 2020 25;2020:9569126. Epub 2020 Jan 25.

Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 21 Shengli Road, 430021 Wuhan, Hubei, China.

There could be an overlap of monogenic diabetes and early-onset type 2 diabetes mellitus. Precise diagnosis of early-onset diabetes has proven valuable for understanding the mechanism of diabetes and selecting optimal therapy. The majority of maturity onset diabetes of the young (MODY) pathogenic genes in China is still unknown. In this study, a family with suspected MODY was enrolled. Whole-exome sequencing (WES) was used to analyze the variants of the proband. Variants were filtered according to their frequency, location, functional consequences, and bioinformatics software. Candidate pathogenic variants were validated by Sanger sequencing and tested for cosegregation in other members of the family and nonrelated healthy controls. KEGG (Kyoto Encyclopedia of Genes and Genomes) and PPI (protein-protein interaction) analysis were conducted using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) and the STRING online analysis tools for the candidate pathogenic gene. A total of 123291 variants including 105344 SNPs and 17947 InDels were found in WES. A likely pathogenic rare missense heterozygous mutation in diabetes genes (c.2137C > T, p.His713Tyr in ) was identified, which was a cosegregate in this family and not in nonrelated healthy controls. The position of the mutation in the aminoacid sequence of the gene is highly conserved among the species. 2 significantly enriched KEGG pathways were identified including bta04930, type II diabetes mellitus (, , , , and ), and bta04910, insulin signaling pathway (, , and ). PPI analysis displayed that IRS1 interacts with 3 known pathogenic proteins including INS, KCNJ11, and GCK. We conclude that WES could be an initial option for genetic testing in patients with early-onset diabetes. p.His713Tyr is implicated as a possible pathogenic mutation in monogenic diabetes, which might require further validation, and the precise molecular mechanism underlying the influence of p.His713Tyr on the development of diabetes remains to be determined in the further prospective studies.
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http://dx.doi.org/10.1155/2020/9569126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204210PMC
January 2020

Effect of Different Cooking Methods on Proton Dynamics and Physicochemical Attributes in Spanish Mackerel Assessed by Low-Field NMR.

Foods 2020 Mar 21;9(3). Epub 2020 Mar 21.

School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, Liaoning, China.

The states of protons within food items are highly related to their physical attributes. In this study, the effect of cooking methods including boiling, steaming, roasting and frying on proton dynamics, physicochemical parameters and microstructure of Spanish mackerel was assessed by low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging (MRI) techniques. The treatment of cooking resulted in a significant reduction of proton mobility and declined freedom of protons. The state changes of protons can be monitored easily in an intuitive and non-destructive manner during various cooking process. The treatments of boiling, steaming, roasting and frying resulted in different cooking loss and similar water-holding capability. A significant increase of total carbonyl content and thiobarbituric acid reactive substances was found, while a decrease of the values for free thiols and surface hydrophobicity was observed. The analysis of circular dichroism spectroscopy and cryo-scanning electron microscopy showed significant structural change. The correlation coefficients of R and R from partial least squares (PLS) regression models were more than 0.980, suggesting good correlation between LF-NMR data and hardness, resilience, springiness, chewiness, gumminess, and adhesiveness. Good recoveries and a relatively small coefficient of variation (CV) were obtained from the PLS regression models, indicating good reliability and accuracy in predicting texture parameters for mackerel samples.
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http://dx.doi.org/10.3390/foods9030364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142434PMC
March 2020