Publications by authors named "Sheng Zhang"

1,761 Publications

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ID1 marks the tumorigenesis of pancreatic ductal adenocarcinoma in mouse and human.

Sci Rep 2022 Aug 8;12(1):13555. Epub 2022 Aug 8.

Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease that has an increasing death rate but no effective treatment to now. Although biological and immunological hallmarks of PDAC have been frequently reported recently, early detection and the particularly aggressive biological features are the major challenges remaining unclear. In the current study, we retrieved multiple scRNA-seq datasets and illustrated the genetic programs of PDAC development in genetically modified mouse models. Notably, the transcription levels of Id1 were elevated specifically along with the PDAC development. Pseudotime trajectory analysis revealed that Id1 was closely correlated with the malignancy of PDAC. The gene expression patterns of human PDAC cells were determined by the comparative analysis of the scRNA-seq data on human PDAC and normal pancreas tissues. ID1 levels in human PDAC cancer cells were dramatically increased compared to normal epithelial cells. ID1 deficiency in vitro significantly blunt the invasive tumor-formation related phenotypes. IPA analysis on the differentially expressed genes suggested that EIF2 signaling was the core pathway regulating the development of PDAC. Blocking EFI2 signaling remarkably decreased the expression of ID1 and attenuated the tumor-formation related phenotypes. These observations confirmed that ID1 was regulated by EIF2 signaling and was the critical determinator of PDAC development and progression. This study suggests that ID1 is a potential malignant biomarker of PDAC in both mouse models and human and detecting and targeting ID1 may be a promising strategy to treat or even rescue PDAC.
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http://dx.doi.org/10.1038/s41598-022-17827-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359991PMC
August 2022

Ventilation indices for evaluation of airborne infection risk control performance of air distribution.

Build Environ 2022 Aug 31;222:109440. Epub 2022 Jul 31.

Division of Building Science and Technology, City University of Hong Kong, China.

Air distribution is an effective engineering measure to fight against respiratory infectious diseases like COVID-19. Ventilation indices are widely used to indicate the airborne infection risk of respiratory infectious diseases due to the practical convenience. This study investigates the relationships between the ventilation indices and airborne infection risk to suggest the proper ventilation indices for the evaluation of airborne infection risk control performance of air distribution. Besides the commonly used ventilation indices of the age of air (), air change effectiveness (), and contaminant removal effectiveness (), this study introduces two ventilation indices, ., the air utilization effectiveness () and contaminant dispersion index (). CFD simulations of a hospital ward and a classroom served by different air distributions, including mixing ventilation, displacement ventilation, stratum ventilation and downward ventilation, are validated to calculate the ventilation indices and airborne infection risk. A three-step correlation analysis based on Spearman's rank correlation coefficient, Pearson correlation coefficient, and goodness of fit and a min-max normalization-based error analysis are developed to qualitatively and quantitatively test the validity of ventilation indices respectively. The results recommend the integrated index of and to indicate the overall airborne infection risk and to indicate the local airborne infection risk respectively regardless of the effects of air distribution, supply airflow rate, infectivity intensity, room configuration and occupant distribution. This study contributes to airborne transmission control of infectious respiratory diseases with air distribution.
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http://dx.doi.org/10.1016/j.buildenv.2022.109440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339087PMC
August 2022

Low-dose intravenous plus inhaled versus intravenous polymyxin B for the treatment of extensive drug-resistant Gram-negative ventilator-associated pneumonia in the critical illnesses: a multi-center matched case-control study.

Ann Intensive Care 2022 Aug 8;12(1):72. Epub 2022 Aug 8.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai, 201801, China.

Background: The mortality of extensively drug-resistant Gram-negative (XDR GN) bacilli-induced ventilator-associated pneumonia (VAP) is extremely high. The purpose of this study was to compare the efficacy and safety of inhaled (IH) plus intravenous (IV) polymyxin B versus IV polymyxin B in XDR GN bacilli VAP patients.

Methods: A retrospective multi-center observational cohort study was performed at eight ICUs between January 1 2018, and January 1 2020 in China. Data from all patients treated with polymyxin B for a microbiologically confirmed VAP were analyzed. The primary endpoint was the clinical cure of VAP. The favorable clinical outcome, microbiological outcome, VAP-related mortality and all-cause mortality during hospitalization, and side effects related with polymyxin B were secondary endpoints. Favorable clinical outcome included clinical cure or clinical improvement.

Results: 151 patients and 46 patients were treated with IV polymyxin B and IH plus IV polymyxin B, respectively. XDR Klebsiella pneumoniae was the main isolated pathogen (n = 83, 42.1%). After matching on age (± 5 years), gender, septic shock, and Apache II score (± 4 points) when polymyxin B was started, 132 patients were included. 44 patients received simultaneous IH plus IV polymyxin B and 88 patients received IV polymyxin B. The rates of clinical cure (43.2% vs 27.3%, p = 0.066), bacterial eradication (36.4% vs 23.9%, p = 0.132) as well as VAP-related mortality (27.3% vs 34.1%, p = 0.428), all-cause mortality (34.1% vs 42.0%, p = 0.378) did not show any significant difference between the two groups. However, IH plus IV polymyxin B therapy was associated with improved favorable clinical outcome (77.3% vs 58.0%, p = 0.029). Patients in the different subgroups (admitted with medical etiology, infected with XDR K. pneumoniae, without bacteremia, with immunosuppressive status) were with odd ratios (ORs) in favor of the combined therapy. No patient required polymyxin B discontinuation due to adverse events. Additional use of IH polymyxin B (aOR 2.63, 95% CI 1.06, 6.66, p = 0.037) was an independent factor associated with favorable clinical outcome.

Conclusions: The addition of low-dose IH polymyxin B to low-dose IV polymyxin B did not provide efficient clinical cure and bacterial eradication in VAP caused by XDR GN bacilli. Keypoints Additional use of IH polymyxin B was the sole independent risk factor of favorable clinical outcome. Patients in the different subgroups were with HRs substantially favoring additional use of IH polymyxin B. No patients required polymyxin B discontinuation due to adverse events.
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http://dx.doi.org/10.1186/s13613-022-01033-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357592PMC
August 2022

One-pot fabrication of nanozyme with 2D/1D heterostructure by in-situ growing MoS nanosheets onto single-walled carbon nanotubes with enhanced catalysis for colorimetric detection of glutathione.

Anal Chim Acta 2022 Aug 14;1221:340083. Epub 2022 Jun 14.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, 150090, PR China; Huzhou Key Laboratory of Medical and Environmental Application Technologies, School of Life Sciences, Huzhou University, Zhejiang, 313000, PR China. Electronic address:

A nanozyme with 2D/1D heterostructure has been fabricated by the in-situ growth of molybdenum disulfide nanosheets (MoS NSs) onto single-walled carbon nanotubes (SWCNTs). It was discovered that the so-obtained [email protected] nanozyme could exhibit greatly improved peroxidase-like catalysis, due to that the formed 2D/1D interfacial coupling in the heterostructure might provide more active sites and exhibit enhanced charge transferring during the catalytic reactions, as confirmed by the X-ray photoelectron spectroscopy, photoluminescence, electrochemical impedance spectra and radical capturing experiments. Furthermore, the catalysis of the developed nanozyme could be selectively inhibited by glutathione (GSH) through the competitive consumption of hydroxyl radicals with enzyme substrate in the catalytic reaction system. A [email protected] catalysis-based colorimetric strategy was further proposed for the quantitative analysis of GSH with the concentrations linearly ranging from 0.01 to 1000.0 μM. Besides, the feasibility of the developed colorimetric method was evaluated by monitoring GSH separately in the extractions from hela cells and human serum, promising the extensive applications for monitoring various biological species like GSH in the clinical laboratory. Importantly, such a fabrication route for nanozyme with 2D/1D heterostructure may pave the way towards the wide applications for designing various nanzymes with improved catalysis.
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http://dx.doi.org/10.1016/j.aca.2022.340083DOI Listing
August 2022

A Phosphoproteomics Study of the Soybean Mutant Revealed Type II Metacaspases Involved in Cell Death Pathway.

Front Plant Sci 2022 19;13:882561. Epub 2022 Jul 19.

Department of Agronomy, Iowa State University, Ames, IA, United States.

The soybean () mutation causes progressive browning of the roots soon after germination and provides increased tolerance to the soil-borne oomycete pathogen in soybean. Toward understanding the molecular basis of the mutant phenotypes, we conducted tandem mass tag (TMT)-labeling proteomics and phosphoproteomics analyses of the root tissues of the mutant and progenitor T322 line to identify potential proteins involved in manifestation of the mutant phenotype. We identified 3,160 proteins. When the -value was set at ≤0.05 and the fold change of protein accumulation between and T322 at ≥1.5 or ≤0.67, we detected 118 proteins that showed increased levels and 32 proteins decreased levels in as compared to that in T322. The differentially accumulated proteins (DAPs) are involved in several pathways including cellular processes for processing environmental and genetic information, metabolism and organismal systems. Five pathogenesis-related proteins were accumulated to higher levels in the mutant as compared to that in T322. Several of the DAPs are involved in hormone signaling, redox reaction, signal transduction, and cell wall modification processes activated in plant-pathogen interactions. The phosphoproteomics analysis identified 22 phosphopeptides, the levels of phosphorylation of which were significantly different between and T322 lines. The phosphorylation levels of two type II metacaspases were reduced in as compared to T322. Type II metacaspase has been shown to be a negative regulator of hypersensitive cell death. In absence of the functional Rn1 protein, two type II metacaspases exhibited reduced phosphorylation levels and failed to show negative regulatory cell death function in the soybean mutant. We hypothesize that Rn1 directly or indirectly phosphorylates type II metacaspases to negatively regulate the cell death process in soybean roots.
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http://dx.doi.org/10.3389/fpls.2022.882561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344878PMC
July 2022

Deep potential for a face-centered cubic Cu system at finite temperatures.

Phys Chem Chem Phys 2022 Aug 3;24(30):18361-18369. Epub 2022 Aug 3.

Institute of Modern Physics, Chinese Academy of Science, Lanzhou 730000, China.

The state-of-the-art method generating potential functions used in molecular dynamics is based on machine learning with neural networks, which is critical for molecular dynamics simulation. This method provides an efficient way for fitting multi-variable nonlinear functions, attracting extensive attention in recent years. Generally, the quality of potentials fitted by neural networks is heavily affected by training datasets and the training process and could be ensured by comprehensively verificating the model accuracy. In this study, we obtained the neural network potential of face-centered cubic (FCC) Cu with the most accurate and adequate training datasets from first-principle calculations and the training process performed by Deep Potential Molecular Dynamics (DeePMD). This potential could not only succeed in reproductions of the variety of properties of Cu at 0 K, but also have a good performance at finite temperatures, such as predicting elastic constants and the melting point. Moreover, our potential has a better generalization capacity to predict the grain boundary energy without including extra datasets about grain boundary structures. These results support the applicability of the method under more practical conditions.
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http://dx.doi.org/10.1039/d2cp02758eDOI Listing
August 2022

Value of rest F-FDG myocardial imaging in the diagnosis of obstructive coronary artery disease in Chinese patients with suspected unstable angina: A prospective real-world clinical study.

J Nucl Cardiol 2022 Aug 1. Epub 2022 Aug 1.

Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, No.185, Juqian Street, Changzhou, 213003, Jiangsu Province, China.

Background: This study aimed to determine the clinical value of rest F-FDG imaging in Chinese patients with non-acute chest pain, normal ECG, negative troponin, and suspected UA.

Methods: 136 patients were prospectively included and underwent rest F-FDG PET imaging and coronary arteriography within 1 week.

Results: Obstructive CAD was diagnosed in 71 patients, and stenosis ≥ 70% was confirmed in 130 vascular territories. At patients and vascular level, rest F-FDG imaging showed sensitivity of 62.0%, 47.7%, specificity of 92.3%, 94.2%, accuracy of 76.5%, 79.4%, PPV of 89.8% and 79.5%, and NPV of 69.0% and 79.4%. The AUCs were 0.771 and 0.710. Of 71 patients with obstructive CAD, rest F-FDG imaging showed sensitivity of 47.7% and 58.8%, specificity of 91.6% and 91.2%, accuracy of 64.8% and 80.4%, PPV of 89.9% and 76.9% and NPV of 52.8% and 81.6% in all vascular level and single-vessel disease. In patients with two- or three-vessel disease, rest F-FDG imaging had a diagnostic sensitivity, specificity, accuracy, PPV, and NPV of 43.8%, 93.3%, 50.5%, 97.7%, and 20.6%. The AUCs were 0.696, 0.750, and 0.685.

Conclusion: Rest F-FDG imaging performed certain overall diagnostic efficiency for obstructive CAD in Chinese patients with suspected UA, especially the excellent high PPV in identifying culprit ischemic territory in patients with multivessel disease.
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http://dx.doi.org/10.1007/s12350-022-03068-4DOI Listing
August 2022

Multi-Omics Uncover Neonatal Cecal Cell Development Potentials.

Front Cell Dev Biol 2022 15;10:840298. Epub 2022 Jul 15.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

Although, the cecum plays vital roles in absorption of water, electrolytes, and other small molecules, and harbors trillions of commensal bacteria to shape large intestine immune functions, it is unknown the cecum development potentials at single cell level during the very crucial neonatal developmental period. Using singe cell RNA-seq and proteomics, we have characterized six major types of cecal cells: undifferentiated cells; immune cells (Ims); cecumocytes (CCs); goblet, Paneth like cells (PLCs), and enteroendocrine cells (EECs) with specific markers. CCs mature with a gradual decrease in proportion of cells; however, Ims develop with a continuing increase in proportion of cells. Meanwhile, goblet and EEC cells reduced in proportion of cells from do to d14 or d21; PLCs increased in proportion of cells from d0 to d7 then decreased at d14 and d21. The cells exhibit specific development and maturation trends controlled by transcriptional factors, ligand-receptor pairs, and other factors. As piglets grow, cecal content and mucosal microbial diversity increases dramatically with population of beneficial microbiota, such as . Moreover, cecal mucosal-associated and cecal content microbiota are positively correlated and both show significant correlation with different types of cecal cells and plasma metabolites. This is the first presentation of neonatal cecal cell development and maturation naturally at single cell level with transcript, protein, microbiota and metabolism perspectives. Furthermore, this study provides an important tool for the determination of novel interventions in cecal drug delivery and metabolism studies.
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http://dx.doi.org/10.3389/fcell.2022.840298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334561PMC
July 2022

Mechanistic Insights into OC-COH Coupling in CO Electroreduction on Fragmented Copper.

J Am Chem Soc 2022 Aug 29;144(31):14005-14011. Epub 2022 Jul 29.

School of Materials Science and Engineering and Key Laboratory of Efficient Utilization of Low and Medium Grade Energy, Tianjin University, Tianjin 300350, People's Republic of China.

The carbon-carbon (C-C) bond formation is essential for the electroconversion of CO into high-energy-density C products, and the precise coupling pathways remain controversial. Although recent computational investigations have proposed that the OC-COH coupling pathway is more favorable in specific reaction conditions than the well-known CO dimerization pathway, the experimental evidence is still lacking, partly due to the separated catalyst design and mechanistic/spectroscopic exploration. Here, we employ density functional theory calculations to show that on low-coordinated copper sites, the *CO bindings are strengthened, and the adsorbed *CO coupling with their hydrogenation species, *COH, receives precedence over CO dimerization. Experimentally, we construct a fragmented Cu catalyst with abundant low-coordinated sites, exhibiting a 77.8% Faradaic efficiency for C products at 300 mA cm. With a suite of spectroscopic studies, we capture an *OCCOH intermediate on the fragmented Cu surfaces, providing direct evidence to support the OC-COH coupling pathway. The mechanistic insights of this research elucidate how to design materials in favor of OC-COH coupling toward efficient C production from CO reduction.
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http://dx.doi.org/10.1021/jacs.2c01044DOI Listing
August 2022

Palladium-Catalyzed -C-H Bond Amination of 2-Aryl Chloromethylbenzenes.

J Org Chem 2022 Aug 28;87(15):10531-10538. Epub 2022 Jul 28.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.

Palladium-catalyzed -C-H bond amination of 2-aryl chloromethylbenzenes is described for the first time. The reactions of 2-aryl chloromethylbenzenes with cyclic amines proceeded smoothly in the presence of Pd(acac), tri(2-furyl)phosphine, and NaH in tetrahydrofuran at 40 °C to provide -C-H bond aminated products in satisfactory to high yields with acceptable regioselectivity in most cases. The electronic property of the substituents linked to the benzene rings did not significantly influence the reactivity of the 2-aryl chloromethylbenzene substrates and the reaction regioselectivity.
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http://dx.doi.org/10.1021/acs.joc.2c01233DOI Listing
August 2022

Instant messaging client gives the opportunity to recognize gut microbiota and dysbiosis-related disease: An investigation study on WeChat APP.

Digit Health 2022 Jan-Dec;8:20552076221115018. Epub 2022 Jul 21.

Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Objectives: Gut microbiota and dysbiosis are closely related to the occurrence and development of various diseases. It is necessary to popularize gut microbiota-related knowledge to the public. And the instant messaging client on smartphones supplies a perfect tool to achieve this goal. Hence, we will describe the current status of gut microbiota education spread by WeChat official accounts.

Methods: The keywords of "gut microbiota," "fecal microbiota transplantation (FMT)," and "probiotics" were searched in the articles published from January 2015 to August 2020 on the WeChat official accounts. And the data were analyzed based on the 10 common gut dysbiosis-related diseases.

Results: A total of 3061 WeChat official accounts have published 11,239 articles on gut microbiota dysbiosis-related diseases, with a rising trend in the total article numbers and the total pageviews. The keywords of "gut microbiota" dominate 50.61%, and the articles on inflammatory bowel disease had the largest proportion. Additionally, articles on the keyword "gut microbiota" also included cancer and obesity, articles on the keyword "FMT" mainly consist of infection and psychological disease, and the keyword "probiotics" was mainly related to obesity and irritable bowel syndrome disease. The top three total pageviews were on inflammatory bowel disease, obesity, and cancer.

Conclusion: This study indicates the current research hotspots and public concerns on the gut microbiota, and WeChat as an instant messaging client plays an important role in promoting the scientific popularization of gut microbiota.
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http://dx.doi.org/10.1177/20552076221115018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309781PMC
July 2022

The Fabrication and Characterization of Pickering Emulsion Gels Stabilized by Sorghum Flour.

Foods 2022 Jul 12;11(14). Epub 2022 Jul 12.

School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China.

Pickering emulsion gels have potential application as solid fat substitutes and nutraceutical carriers in foods, but a safe and easily available food-derived particle emulsifier is the bottleneck that limits their practical application. In this study, the function of sorghum flour as a particle emulsifier to stabilize the oil-in-water (O/W) Pickering emulsion gels with medium chain triglycerides (MCT) in the oil phase was introduced. Sorghum flour had suitable size distribution (median diameter, 21.47 μm) and wettability (contact angle, 38°) and could reduce the interfacial tension between MCT and water. The oil phase volume fraction () and the addition amount of sorghum flour () had significant effects on the formation of Pickering emulsion gels. When c ≥ 5%, Pickering emulsion gels with = 70% could be obtained. Microstructure analysis indicated that sorghum flour not only played an emulsifying role at the O/W interface but also prevented oil droplets from coalescing through its viscous effect in the aqueous phase. With increases in , the droplet size of the emulsion gel decreased, its mechanical properties gradually strengthened, and its protective effect on β-carotene against UV irradiation also improved.
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http://dx.doi.org/10.3390/foods11142056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315638PMC
July 2022

Remaining Useful Life Prediction Model for Rolling Bearings Based on MFPE-MACNN.

Entropy (Basel) 2022 Jun 30;24(7). Epub 2022 Jun 30.

Key Laboratory of Advanced Manufacturing and Intelligent Technology of Ministry of Education, Harbin University of Science and Technology, Harbin 150080, China.

Aiming to resolve the problem of redundant information concerning rolling bearing degradation characteristics and to tackle the difficulty faced by convolutional deep learning models in learning feature information in complex time series, a prediction model for remaining useful life based on multiscale fusion permutation entropy (MFPE) and a multiscale convolutional attention neural network (MACNN) is proposed. The original signal of the rolling bearing was extracted and decomposed by resonance sparse decomposition to obtain the high-resonance and low-resonance components. The multiscale permutation entropy of the low-resonance component was calculated. Moreover, the locally linear-embedding algorithm was used for dimensionality reduction to remove redundant information. The multiscale convolution module was constructed to learn the feature information at different time scales. The attention module was used to fuse the feature information and input it into the remaining useful life prediction module for evaluation. The appropriate network structure and parameter configuration were determined, and a multiscale convolutional attention neural network was designed to determine the remaining useful life prediction model. The results show that the method demonstrates effectiveness and superiority in degrading the feature information representation and improving the remaining useful life prediction accuracy compared with other models.
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http://dx.doi.org/10.3390/e24070905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321675PMC
June 2022

Xylooligosaccharide-mediated gut microbiota enhances gut barrier and modulates gut immunity associated with alterations of biological processes in a pig model.

Carbohydr Polym 2022 Oct 26;294:119776. Epub 2022 Jun 26.

State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100093, PR China. Electronic address:

Xylooligosaccharide (XOS) has tremendous prebiotic potentials for gut health, but the relevant mechanisms are unclear. Herein, we confirmed the positive effects of dietary XOS enhancing gut barrier in a pig model via suppressing the expression of pro-inflammatory cytokines (IL-6 and IL-8). Meanwhile, XOS increased beneficial microbes Lactobacillus and decreased potential pathogenic bacteria. Moreover, XOS augmented microbiota-derived metabolites (mainly butyrate, propionate, and secondary bile acid) to strengthen the gut barrier and regulate gut immunity through activating host G-protein coupled receptors 109a or inhibiting histone deacetylases. Furthermore, XOS attenuated IgA-production and antigen cross-presentation processes. In addition, XOS supplementation led to the alteration of cell proliferation, remodeling of the energy metabolism, activation processes of serial genes or proteins, increased molecular chaperones, and the enhanced ubiquitin-proteasome pathway in cecal cells. Collectively, these results suggest that XOS enhances gut barrier and modulates gut immunity by optimizing gut microbiota and their metabolites, which is associated with alterations of biological processes.
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http://dx.doi.org/10.1016/j.carbpol.2022.119776DOI Listing
October 2022

14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing.

Sci Adv 2022 Jul 22;8(29):eabn3773. Epub 2022 Jul 22.

Department of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.

Recent studies demonstrate that α cells contribute to glucose-stimulated insulin secretion (GSIS). Glucagon-like peptide-1 receptor (GLP-1R) agonists potently potentiate GSIS, making these drugs useful for diabetes treatment. However, the role of α and β cell paracrine interactions in the effects of GLP-1R agonists is undefined. We previously found that increased β cell GLP-1R signaling activates α cell GLP-1 expression. Here, we characterized the bidirectional paracrine cross-talk by which α and β cells communicate to mediate the effects of the GLP-1R agonist, liraglutide. We find that the effect of liraglutide to enhance GSIS is blunted by α cell ablation in male mice. Furthermore, the effect of β cell GLP-1R signaling to activate α cell GLP-1 is mediated by a secreted protein factor that is regulated by the signaling protein, 14-3-3-zeta, in mouse and human islets. These data refine our understanding of GLP-1 pharmacology and identify 14-3-3-zeta as a potential target to enhance α cell GLP-1 production.
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http://dx.doi.org/10.1126/sciadv.abn3773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307243PMC
July 2022

Extradural Contralateral Ventral Root Transfer to Treat Lower Limb Motor Dysfunction in Paraplegia.

Spine (Phila Pa 1976) 2022 09 14;47(17):1253-1258. Epub 2022 Jul 14.

Department of Orthopedics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Study Design: Eight cadavers were included in this anatomical study.

Objective: This study aimed to confirm the anatomical feasibility of extradural transfer of the contralateral T11 ventral root (VR) to the ipsilateral L2 level and the contralateral L1 VR to the ipsilateral L3 level to restore lower limb function in cases of paraplegia.

Summary Of Background Data: Motor dysfunction due to hemiplegia significantly affects the daily life of patients. To date, unlike in cases of upper limb dysfunction, there are few studies on the surgical management of lower limb movement dysfunction.

Materials And Methods: Eight cadavers were included in this study to confirm the feasibility of the nerve transfer. After separating the VR and dorsal root at each level, the VRs at the T11 and L1 levels were anastomosed with the VRs of L2 and L3, respectively. The length of the VRs of donor roots and the distance between the donor and recipient nerves were measured. H&E staining was performed to verify the number of axons and the cross-sectional area of the VRs. Lumbar x-rays of 60 healthy adults were used to measure the distance between the donor and recipient nerves.

Results: After exposing the bilateral extradural each root, the VRs could be easily isolated from the whole root. The distance between the VRs of T11 and L2, L1, and L3 was significantly longer than the length of the donor nerve. Therefore, the sural nerve was used for grafting. The measurements performed on the lumbar x-rays of the 60 healthy adults confirmed the results. The number of axons and cross-sectional area of the VRs were measured.

Conclusion: Our study confirmed the anatomical feasibility of transferring the VRs of T11 to L2 and that of L1 to L3 to restore lower limb function in cases of hemiplegia.

Level Of Evidence: 5.
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http://dx.doi.org/10.1097/BRS.0000000000004373DOI Listing
September 2022

HAP40 is a conserved central regulator of Huntingtin and a potential modulator of Huntington's disease pathogenesis.

PLoS Genet 2022 Jul 19;18(7):e1010302. Epub 2022 Jul 19.

The Brown Foundation Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, United States of America.

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, HAP40 strongly affected HTT's stability, as depletion of HAP40 significantly reduced the levels of endogenous HTT protein while HAP40 overexpression markedly extended its half-life. Conversely, in the absence of HTT, the majority of HAP40 protein were degraded, likely through the proteasome. Further, the affinity between HTT and HAP40 was not significantly affected by polyglutamine expansion in HTT, and contrary to an early report, there were no abnormal accumulations of endogenous HAP40 protein in HD cells from mouse HD models or human patients. Lastly, when tested in Drosophila models of HD, HAP40 partially modulated the neurodegeneration induced by full-length mutant HTT while showed no apparent effect on the toxicity of mutant HTT exon 1 fragment. Together, our study uncovers a conserved mechanism governing the stability and in vivo functions of HTT and demonstrates that HAP40 is a central and positive regulator of endogenous HTT. Further, our results support that mutant HTT is toxic regardless of the presence of its partner HAP40, and implicate HAP40 as a potential modulator of HD pathogenesis through its multiplex effect on HTT's function, stability and the potency of mutant HTT's toxicity.
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http://dx.doi.org/10.1371/journal.pgen.1010302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295956PMC
July 2022

Vortioxetine Modulates the Regional Signal in First-Episode Drug-Free Major Depressive Disorder at Rest.

Front Psychiatry 2022 29;13:950885. Epub 2022 Jun 29.

Department of Spine and Orthopedics, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China.

Background: Previous studies on brain functional alterations associated with antidepressants for major depressive disorder (MDD) have produced conflicting results because they involved short treatment periods and a variety of compounds.

Methods: Resting-state functional magnetic resonance imaging scans were obtained from 25 first-episode drug-free patients with MDD and 25 healthy controls. The patients, who were treated with vortioxetine for 8 weeks, were scanned at two-time points (baseline and week 8 of treatment). The amplitude of low-frequency fluctuation (ALFF) in the imaging data was used to analyze local brain signal alterations associated with antidepressant treatment.

Results: Compared with the controls, the patients at baseline showed decreased ALFF values in the right inferior temporal gyrus and increased ALFF values in the left inferior cerebellum, right cingulate gyrus and postcentral gyrus. After 8 weeks of vortioxetine treatment, patients showed increased ALFF values in the bilateral cingulate gyrus, middle temporal gyrus, medial superior frontal gyrus, and inferior cerebellum.

Conclusion: This study provided evidence that vortioxetine modulates brain signals in MDD sufferers. These findings contribute to the understanding of how antidepressants effect brain function.
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http://dx.doi.org/10.3389/fpsyt.2022.950885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277001PMC
June 2022

Tumor-derived exosomes in the cancer immune microenvironment and cancer immunotherapy.

Cancer Lett 2022 Jul 11:215823. Epub 2022 Jul 11.

Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China; Shenyang Clinical Medical Research Center for Diagnosis, Treatment and Health Management of Early Digestive Cancer, Shenyang, 110032, China. Electronic address:

Tumor-derived exosomes (TDEs) are key immune regulators in the tumor microenvironment. They have been shown to reshape the immune microenvironment and prevent antitumor immune responses via their immunosuppressive cargo, thereby determining responsiveness to cancer therapy. By delivering suppressive cargo to the immune cells, TDEs directly or indirectly influence the functions and antitumor activities of immune cells. TDE-based therapy is emerging as a cutting-edge and promising strategy for inhibiting tumor progression or enhancing antitumor immunity. Therefore, in this study, we reviewed the mechanism by which TDEs regulate immune cells and their applications in immunotherapy.
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http://dx.doi.org/10.1016/j.canlet.2022.215823DOI Listing
July 2022

Realgar-induced nephrotoxicity via ferroptosis in mice.

J Appl Toxicol 2022 Jul 8. Epub 2022 Jul 8.

Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Ferroptosis is a novel form of iron-dependent cell death that is involved in arsenic-induced toxicity. Realgar is an arsenic-containing Chinese medicine, which can result in nephrotoxicity because of long-term exposure. However, it remains scientifically unknown whether Realgar is an inducer of ferroptosis in the kidney. This study investigated the role of ferroptosis in Realgar-induced kidney toxicity in mice. ICR mice were exposed to Realgar for 28 days, and HK2 cells were exposed to Realgar in the presence or absence of treatment with ferrostatin-1, a ferroptosis inhibitor. The ferroptosis-related indicators were further evaluated. Realgar can cause nephrotoxicity in mice by continuous gavage for 28 days, accompanied by an increase in iron accumulation and reactive oxygen species (ROS). The reduced expression of Slc7A11 and Gpx4 further confirmed the ferroptosis mediated by Realgar. Meanwhile, Realgar disrupted the antioxidant system as evidenced by the formation of ROS leading to the inactivation of antioxidant enzymes. Realgar caused ferroptosis in a dose-dependent manner, which was significantly reduced by ferrostatin-1 in HK2 cells. This study revealed that Realgar-induced ferroptosis triggered nephrotoxicity in mice and provided new clues to elucidate the mechanism of Realgar-induced nephrotoxicity.
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http://dx.doi.org/10.1002/jat.4362DOI Listing
July 2022

Identifying potential biomarkers and therapeutic targets for dogs with sepsis using metabolomics and lipidomics analyses.

PLoS One 2022 8;17(7):e0271137. Epub 2022 Jul 8.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.

Sepsis is a diagnostic and therapeutic challenge and is associated with morbidity and a high risk of death. Metabolomic and lipidomic profiling in sepsis can identify alterations in metabolism and might provide useful insights into the dysregulated host response to infection, but investigations in dogs are limited. We aimed to use untargeted metabolomics and lipidomics to characterize metabolic pathways in dogs with sepsis to identify therapeutic targets and potential diagnostic and prognostic biomarkers. In this prospective observational cohort study, we examined the plasma metabolomes and lipidomes of 20 healthy control dogs and compared them with those of 21 client-owned dogs with sepsis. Patient data including signalment, physical exam findings, clinicopathologic data and clinical outcome were recorded. Metabolites were identified using an untargeted mass spectrometry approach and pathway analysis identified multiple enriched metabolic pathways including pyruvaldehyde degradation; ketone body metabolism; the glucose-alanine cycle; vitamin-K metabolism; arginine and betaine metabolism; the biosynthesis of various amino acid classes including the aromatic amino acids; branched chain amino acids; and metabolism of glutamine/glutamate and the glycerophospholipid phosphatidylethanolamine. Metabolites were identified with high discriminant abilities between groups which could serve as potential biomarkers of sepsis including 13,14-Dihydro-15-keto Prostaglandin A2; 12(13)-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid); and 9-HpODE (9-Hydroxyoctadecadienoic acid). Metabolites with higher abundance in samples from nonsurvivors than survivors included 3-(2-hydroxyethyl) indole, indoxyl sulfate and xanthurenic acid. Untargeted lipidomic profiling revealed multiple sphingomyelin species (SM(d34:0)+H; SM(d36:0)+H; SM(d34:0)+HCOO; and SM(d34:1D3)+HCOO); lysophosphatidylcholine molecules (LPC(18:2)+H) and lipophosphoserine molecules (LPS(20:4)+H) that were discriminating for dogs with sepsis. These biomarkers could aid in the diagnosis of dogs with sepsis, provide prognostic information, or act as potential therapeutic targets.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271137PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269464PMC
July 2022

Acetic acid alters rhizosphere microbes and metabolic composition to improve willows drought resistance.

Sci Total Environ 2022 Jul 4;844:157132. Epub 2022 Jul 4.

Key Laboratory for Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China. Electronic address:

The adverse effects of drought on plants are gradually exacerbated with global climatic change. Amelioration of the drought stress that is induced by low doses of acetic acid (AA) has been caused great interest in plants. However, whether AA can change soil microbial composition is still unknown. Here, we investigated how exogenous AA regulates the physiology, rhizosphere soil microorganisms and metabolic composition on Salix myrtillacea under drought stress. The physiological results showed that AA could improve the drought tolerance of S. myrtillacea. Azotobacter and Pseudomonas were enriched in the rhizosphere by AA irrigation. AA significantly increased the relative contents of amino acid metabolites (e.g., glycyl-L-tyrosine, l-glutamine and seryl-tryptophan) and decreased the relative contents of phenylpropane metabolites (e.g., fraxetin and sinapyl aldehyde) in soils. The enrichments of Azotobacter and Pseudomonas were significantly correlated with glycyl-L-tyrosine, l-glutamine, seryl-tryptophan, fraxetin and sinapyl aldehyde, which could increase the stress resistance by promoting nitrogen (N) uptake for willows. Furthermore, inoculation with Azotobacter chroococcum and Pseudomonas fluorescens could significantly improve willows drought tolerance. Therefore, our results reveal that the changes of plant physiology, rhizosphere soil microorganisms and metabolic composition induced by AA can improve willows drought resistance by enhancing N uptake.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157132DOI Listing
July 2022

Design and validation of a new scale for prehospital evaluation of stroke and large vessel occlusion.

Ther Adv Neurol Disord 2022 30;15:17562864221104511. Epub 2022 Jun 30.

Center for Rehabilitation Medicine, Department of Neurology, People's Hospital of Hangzhou Medical College, Zhejiang Provincial People's Hospital, 158# Shangtang Road, Hangzhou 310014, Zhejiang, China.

Background: Rapid recognition of acute stroke and large vessel occlusion (LVO) is essential in prehospital triage for timely reperfusion treatment.

Objective: This study aimed to develop and validate a new screening tool for both stroke and LVO in an urban Chinese population.

Methods: This study included patients with suspected stroke who were transferred to our hospital by emergency medical services between July 2017 and June 2021. The population was randomly partitioned into training (70%) and validation (30%) groups. The Staring-Hypertension-atrIal fibrillation-sPeech-weakneSs (SHIPS) scale, consisting of both clinical and medical history information, was generated based on multivariate logistic models. The predictive ability of the SHIPS scale was evaluated and compared with other scales using receiver operating characteristic (ROC) curve comparison analysis.

Results: A total of 400 patients were included in this analysis. In the training group ( = 280), the SHIPS scale showed a sensitivity of 90.4% and specificity of 60.8% in predicting stroke and a sensitivity of 75% and specificity of 61.5% in predicting LVO. In the validation group ( = 120), the SHIPS scale was not inferior to Stroke 1-2-0 ( = 0.301) in predicting stroke and was significantly better than the Cincinnati Stroke Triage Assessment Tool (C-STAT; formerly CPSSS) and the Prehospital Acute Stroke Severity scale (PASS) (all  < 0.05) in predicting LVO. In addition, including medical history in the scale was significantly better than using symptoms alone in detecting stroke (training group, 0.853 0.818; validation group, 0.814 0.764) and LVO (training group, 0.748 0.722; validation group, 0.825 0.778).

Conclusion: The SHIPS scale may serve as a superior screening tool for stroke and LVO identification in prehospital triage. Including medical history in the SHIPS scale improves the predictive value compared with clinical symptoms alone.
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http://dx.doi.org/10.1177/17562864221104511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251951PMC
June 2022

Social Support and Coping Style of Medical Residents in China: The Mediating Role of Psychological Resilience.

Front Psychiatry 2022 20;13:888024. Epub 2022 Jun 20.

Department of Psychiatry, Wuhan Mental Health Center, Wuhan, China.

Objectives: Recent surveys have paid insufficient attention to the psychological status of medical residents, but medical residents, as a special group of medical workers, need to be focused on. This study aimed to investigate medical residents' levels of social support, psychological resilience, and coping style, and explore the mediating role of psychological resilience, which can ultimately provide a new theoretical basis for improving medical residents' psychological status and quality of work and life.

Methods: A total of 577 medical residents from China were investigated by an online questionnaire, using convenience sampling. Associations between social support, psychological resilience, and coping styles were assessed using Pearson correlation analysis. The mediating effect of psychological resilience was tested using SPSS Process.

Results: Positive correlations between social support, psychological resilience and coping style were found ( = 0.474, < 0.001; = 0.473, < 0.001; = 0.353, < 0.001). The mediating effect of psychological resilience in the relationship between social support and coping style was significant (95% CI: 0.168, 0.384), and accounted for 25.84%.

Conclusion: Attention should be paid to the psychological status of medical residents, and social support and psychological flexibility can be used to increase the enthusiasm for their coping style and promote their mental health.
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http://dx.doi.org/10.3389/fpsyt.2022.888024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251000PMC
June 2022

High-throughput "read-on-ski" automated imaging and label-free detection system for toxicity screening of compounds using personalised human kidney organoids.

J Zhejiang Univ Sci B 2022 Jul;23(7):564-577

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
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http://dx.doi.org/10.1631/jzus.B2100701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264113PMC
July 2022

Effects of strip cropping with reducing row spacing and super absorbent polymer on yield and water productivity of oat (Avena sativa L.) under drip irrigation in Inner Mongolia, China.

Sci Rep 2022 Jul 6;12(1):11441. Epub 2022 Jul 6.

Agriculture and Forestry Sciences of Ulanqab, Jining, 012000, China.

With the serious shortage of water resources and the development of water-saving agriculture, the application of drip irrigation has been paid more and more attention. But there was lack of oat planting methods suitable for drip irrigation, currently. In order to establish an efficient oat planting method for drip irrigation, a study was conducted at Agriculture and Forestry Sciences of Ulanqab, Inner Mongolia during the season (2019-2020) to evaluate the effect of strip cropping with reducing row spacing and super absorbent polymer on the yield and water use efficiency of oat. To conduct the field trials, a split plot system in three replications was established. Three planting patterns were in the main plots, including conventional cropping with 20 cm equal row spacing (PA), strip cropping with the 15 cm row spacing (PB) and strip cropping with the 10 cm row spacing (PC), and two super absorbent polymer levels were in the subplots, including 22.5 kg ha (Y) and 0 (N). The results showed that, compared with PA, PB and PC both decreased the irrigation volumes by 4.5-18.4 mm, and the irrigation volumes of PB was lower than that of PC. When super absorbent polymers were applied, compared with PA, PB significantly increased grain yield and above-ground biomass, but PC had the opposite effects. The grain yield and above-ground biomass of PB significantly increased by 16.65% and 7.31% on average in two years, respectively. And the increasing of grain yield was attributed by the significant increasing of pike number and kernel number per spike. But when super absorbent polymers were not applied, PB had no significant effects on grain yield and above-ground biomass. PB also had the significant effects on regulating water use of oats weather or not super absorbent polymers were applied, it significantly increased the precipitation ratio by 2.64% (PBY) and 2.13% (PBN) and decreased irrigation ration by 3.32% (PBY) and 5.28% (PBN) on average in two years. Although PB and PC both decreased the total evapotranspiration, but PB increased WUE and PC deceased WUE. The WUE of PB increased by 19.70% (PBY) and 9.87% (PBN) on average in two years. Also PB had the highest economic benefits in all treatments. In conclusion, a drip irrigation oat planting pattern was proposed, which the row spacing is 15 cm, adjusted the equal row spacing planting to 8-row strip planting, with a belt spacing of 30 cm, combined with the application of 22.5 kg ha applying super absorbent polymers. And this oat planting pattern is a viable strategy to improve oat productivity.
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http://dx.doi.org/10.1038/s41598-022-15418-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259646PMC
July 2022

Litsea cubeba Essential Oil: Component Analysis, Anti-Candida albicans Activity and Mechanism Based on Molecular Docking.

J Oleo Sci 2022 Aug 12;71(8):1221-1228. Epub 2022 Jul 12.

College of Material and Science, Central South University of Forestry and Technology.

The antifungal mechanism of plant essential oil has always been a concern in the agriculture and forestry science field. In this investigation, besides the evaluation of inhibitory activities of twenty-three essential oils against Candida albicans in vitro, identification and quantification of the chemical composition of Litsea cubeba essential oil by gas chromatography-mass spectrometry were investigated. Further development, we assessed the mechanism of L. cubeba essential oil against C. albicans by molecular docking. Litsea cubeba essential oil displayed the strongest inhibitory activity among these oils and the diameter of the circle against C. albicans was more than 50 mm. Maximum three components were identified with trans-citral (33.6%), cis-citral (30.3%), d-limonene (8.2%). Secretory aspartate protease (SAP5) and β-1,3-glucan synthase (β-1,3-GS) are two key enzyme proteins that inhibit the growth of C. albicans. Molecular docking studies reveal chemical binding forces of cis-citral, trans-citral and d-limonene to SAP5 are -21.76 kJ/mol, -22.18 kJ/mol and -24.27 kJ/mol, to β-1,3-GS are -23.01 kJ/mol, -25.52 kJ/mol and -23.85 kJ/mol, respectively. The most preferable binding mechanism was observed against SAP5 and β-1,3-GS due to hydrophobic interaction, as well as hydrogen bonding between citral molecules. The research results suggest the mechanism of chemical components in L. cubeba essential oil inhibits the growth of C. albicans, which provides a reference to the development and utilization of essential oil.
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http://dx.doi.org/10.5650/jos.ess22108DOI Listing
August 2022

Comparison of Hemodynamic Brain Responses Between Big Wave Surfers and Non-big Wave Surfers During Affective Image Presentation.

Front Psychol 2022 16;13:800275. Epub 2022 Jun 16.

Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Background: Big wave surfers are extreme sports athletes who expose themselves to life-threatening risk when training and competing. Little is known about how and why extreme sports athletes choose to participate in their chosen sports. This exploratory study investigated potential neurophysiological and psychometric differences between big and non-big wave surfers.

Methods: Thirteen big wave surfers (BWS) and 10 non-big wave surfers (CON) viewed a series of images from the International Affective Picture System (IAPS) while undergoing brain functional magnetic resonance imaging (fMRI). The Fear Schedule Survey-III, Arnett Inventory of Sensation Seeking, Discrete Emotions Questionnaire, and Positive and Negative Affect Schedule were also completed.

Results: The BWS group demonstrated higher blood-oxygen level-dependent (BOLD) signal change in the insula, visual cortex, and periaqueductal gray, whereas the CON group displayed increased hypothalamus activation in response to high amplitude negative-valence (HAN) image presentation. Psychophysiological interaction (PPI) analyses found CON showed significant interactions between frontal and temporal cortical regions as well as between the hypothalamus and the insula, frontal, and temporal cortices during HAN image presentation that were not seen in BWS. No differences between groups were found in their responses to the questionnaires.

Conclusion: Our findings demonstrate significant differences in brain activation between BWS and CON in response to the presentation of HAN IAPS images, despite no significant differences in scores on psychometric questionnaires.
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http://dx.doi.org/10.3389/fpsyg.2022.800275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245544PMC
June 2022

The Effect of Elevated Alanine Transaminase on Non-invasive Prenatal Screening Failures.

Front Med (Lausanne) 2022 15;9:875588. Epub 2022 Jun 15.

Department of Obstetrics, School of Gusu, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.

Objective: To determine the effects of alanine transaminase (ALT) levels on the screening failure rates or "no calls" due to low fetal fraction (FF) to obtain a result in non-invasive prenatal screening (NIPS).

Methods: NIPS by sequencing and liver enzyme measurements were performed in 7,910 pregnancies at 12-26 weeks of gestation. Univariate and multivariable regression models were used to evaluate the significant predictors of screening failure rates among maternal characteristics and relevant laboratory parameters.

Results: Of the 7,910 pregnancies that met the inclusion criteria, 134 (1.69%) had "no calls." Multiple logistic regression analysis demonstrated that increased body mass index, ALT, prealbumin, albumin levels, and fertilization (IVF) conception rates were independently associated with screening failures. The test failure rate was higher (4.34 vs. 1.41%; < 0.001) in IVF pregnancies relative to those with spontaneous conceptions. Meanwhile, the screening failure rates increased with increasing ALT levels from 1.05% at ≤10 U/L to 3.73% at >40 U/L. In particular, IVF pregnancies with an ALT level of >40 U/L had a higher test failure rate (9.52%). Compared with that for an ALT level of ≤10 U/L, the adjusted odds ratio of "no calls" for ALT levels of 10-20, 21-40, and >40 U/L was 1.204 [95% confidence interval (CI), 0.709-2.045], 1.529 (95% CI, 0.865-2.702), and 2.764 (95% CI, 1.500-5.093) ( < 0.001), respectively.

Conclusions: Increased ALT and IVF conceptions were associated with a higher screening failure rates in NIPS. Therefore, a feasible strategy to adjust these factors to reduce the probability of "no calls" due to low FF would be of great clinical significance.
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http://dx.doi.org/10.3389/fmed.2022.875588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240308PMC
June 2022

Combination of Androgen Deprivation Therapy with Radical Local Therapy Versus Androgen Deprivation Therapy Alone for Newly Diagnosed Oligometastatic Prostate Cancer: A Phase II Randomized Controlled Trial.

Eur Urol Oncol 2022 Jun 29. Epub 2022 Jun 29.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China; Shanghai Genitourinary Cancer Institute, Shanghai, People's Republic of China; Fudan University Prostate Cancer Institute, Shanghai, People's Republic of China. Electronic address:

Background: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor.

Objective: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa).

Design, Setting, And Participants: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases.

Intervention: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule.

Outcome Measurements And Statistical Analysis: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival.

Results And Limitations: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008).

Conclusions: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone.

Patient Summary: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival.
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http://dx.doi.org/10.1016/j.euo.2022.06.001DOI Listing
June 2022
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