Publications by authors named "Hui Yuan"

413 Publications

A tumor microenvironment-related mRNA-ncRNA signature for prediction early relapse and chemotherapeutic sensitivity in early-stage lung adenocarcinoma.

J Cancer Res Clin Oncol 2021 Jul 21. Epub 2021 Jul 21.

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudand University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.

Objectives: Postoperative early relapse of early-stage lung adenocarcinoma is implicated in poor prognosis. The purpose of our study was to develop an integrated mRNA and non-coding RNA (ncRNA) signature to identify patients at high risk of early relapse in stage I-II lung adenocarcinoma who underwent complete resection.

Methods: Early-stage lung adenocarcinoma data from Gene Expression Omnibus database were divided into training set and testing set. Propensity score matching analysis was performed between patients in early relapse group and long-term nonrelapse group from training set. Transcriptome analysis, random survival forest and LASSO Cox regression model were used to build an early relapse-related multigene signature. The robustness of the signature was evaluated in testing set and RNA-Seq dataset from The Cancer Genome Atlas (TCGA). The chemotherapy sensitivity, tumor microenvironment and mutation landscape related to the signature were explored using bioinformatics analysis.

Results: Twelve mRNAs and one ncRNA were selected. The multigene signature achieved a strong power for early relapse prediction in training set (HR 3.19, 95% CI 2.16-4.72, P < 0.001) and testing set (HR 2.91, 95% CI 1.63-5.20, P = 0.002). Decision curve analyses revealed that the signature had a good clinical usefulness. Groups divided by the signature exhibited different chemotherapy sensitivity, tumor microenvironment characteristics and mutation landscapes.

Conclusions: Our results indicated that the integrated mRNA-ncRNA signature may be an innovative biomarker to predict early relapse of early-stage lung adenocarcinoma, and may provide more effective treatment strategies.
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http://dx.doi.org/10.1007/s00432-021-03718-zDOI Listing
July 2021

Reduced Reference Perceptual Quality Model with Application to Rate Control for Video-based Point Cloud Compression.

IEEE Trans Image Process 2021 Jul 19;PP. Epub 2021 Jul 19.

In rate-distortion optimization, the encoder settings are determined by maximizing a reconstruction quality measure subject to a constraint on the bitrate. One of the main challenges of this approach is to define a quality measure that can be computed with low computational cost and which correlates well with the perceptual quality. While several quality measures that fulfil these two criteria have been developed for images and videos, no such one exists for point clouds. We address this limitation for the video-based point cloud compression (V-PCC) standard by proposing a linear perceptual quality model whose variables are the V-PCC geometry and color quantization step sizes and whose coefficients can easily be computed from two features extracted from the original point cloud. Subjective quality tests with 400 compressed point clouds show that the proposed model correlates well with the mean opinion score, outperforming state-of-the-art full reference objective measures in terms of Spearman rank-order and Pearson linear correlation coefficient. Moreover, we show that for the same target bitrate, rate-distortion optimization based on the proposed model offers higher perceptual quality than rate-distortion optimization based on exhaustive search with a point-to-point objective quality metric. Our datasets are publicly available at https://github.com/qdushl/Waterloo-Point-Cloud-Database-2.0.
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http://dx.doi.org/10.1109/TIP.2021.3096060DOI Listing
July 2021

Risk stratification of ulcer-like projection in uncomplicated acute type B aortic intramural haematoma.

Eur J Cardiothorac Surg 2021 Jul 15. Epub 2021 Jul 15.

School of Medicine, South China University of Technology, Guangzhou, China.

Objectives: This study aimed to investigate the morphological evolution and risk stratification of ulcer-like projection (ULP) in patients with uncomplicated acute type B aortic intramural haematoma.

Methods: A retrospective study was conducted on patients with uncomplicated acute type B intramural haematoma admitted in our institution from January 2015 to June 2020. The primary end points were adverse aortic events (AAE), including aortic rupture, aortic dissection, aortic aneurysm and ULP enlargement.

Results: The study cohort comprised 140 patients, including 62 (44%) and 78 (56%) patients with and without initial ULP, respectively. AAE occurred in 13 patients (9%) in the early term and 42 patients (33%) in the mid-term. Compared with patients without ULP, patients with initial ULP had no significant difference in early outcomes but a higher mid-term AAE rate [8% vs 11%, odds ratio (OR) 1.5, P = 0.47; 17% vs 55%, OR 6.0, P < 0.001]. Significantly higher AAE rate was observed in patients with high-risk ULP (depth ≥5.0 mm and located in the proximal aortic segments) than those with only low-risk ULP (depth <5.0 mm and/or located in the distal aortic segments) (87% vs 51%, OR 6.2, P = 0.014). In the multivariable analysis, high-risk ULP was an independent predictor of AAE (hazard ratio 2.8, P = 0.009).

Conclusions: High-risk ULP is a rapidly evolving entity and a marker of AAE despite optimal medical therapy. Therefore, close follow-up and prompt intervention are recommended for patients with high-risk ULP.
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http://dx.doi.org/10.1093/ejcts/ezab249DOI Listing
July 2021

Evaluation of Nano-Particulate-Matter-Induced Lung Injury in Mice Using Quantitative Micro-Computed Tomography.

J Nanosci Nanotechnol 2021 Dec;21(12):6041-6047

College of Food Science, Shihezi University, Shihezi, 832000, China.

Nano-particulate matters (NPM) induced the lung injury in mice were evaluated using quantitative micro-computed tomography in the present article. It is an important negative effect of health problems that NPM exposure provokes changes in the lung injury. The micro-computed tomography (CT) to assess lung injury in mouse models has been investigated. The dynamic structural changes in a NPM-induced lung injury mouse mode were monitored. Adults female BALB/C mice were repeatedly exposed to NPM, and micro-CT scans were performed at day 0, 3, 5 and 9. Lung samples were also collected for histological analysis at each time point. The total lung volume, the injured lung volume, and the normal lung volume were defined and calculated volume during the phase of NPM-exposure on the mice. The total and injured lung volumes of NPM-exposed mice were significantly larger than those of the mice at day 5 and 9. The data from micro-CT was consistent with alveolar enlargement and destruction by histological quantification from pathological section. The study for NPM-induced lung injury model by micro-CT may extend our understanding of the distinct pathophysiology of NPM induced lung injury in mice.
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http://dx.doi.org/10.1166/jnn.2021.19522DOI Listing
December 2021

Roadmap of Terahertz Imaging 2021.

Sensors (Basel) 2021 Jun 14;21(12). Epub 2021 Jun 14.

Physikalisches Institut, Goethe-Universität, Max-von-Laue Straße 1, D-60438 Frankfurt am Main, Germany.

In this roadmap article, we have focused on the most recent advances in terahertz (THz) imaging with particular attention paid to the optimization and miniaturization of the THz imaging systems. Such systems entail enhanced functionality, reduced power consumption, and increased convenience, thus being geared toward the implementation of THz imaging systems in real operational conditions. The article will touch upon the advanced solid-state-based THz imaging systems, including room temperature THz sensors and arrays, as well as their on-chip integration with diffractive THz optical components. We will cover the current-state of compact room temperature THz emission sources, both optolectronic and electrically driven; particular emphasis is attributed to the beam-forming role in THz imaging, THz holography and spatial filtering, THz nano-imaging, and computational imaging. A number of advanced THz techniques, such as light-field THz imaging, homodyne spectroscopy, and phase sensitive spectrometry, THz modulated continuous wave imaging, room temperature THz frequency combs, and passive THz imaging, as well as the use of artificial intelligence in THz data processing and optics development, will be reviewed. This roadmap presents a structured snapshot of current advances in THz imaging as of 2021 and provides an opinion on contemporary scientific and technological challenges in this field, as well as extrapolations of possible further evolution in THz imaging.
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http://dx.doi.org/10.3390/s21124092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232131PMC
June 2021

Low BDNF levels in serum are associated with cognitive impairments in medication-naïve patients with current depressive episode in BD II and MDD.

J Affect Disord 2021 Jun 18;293:90-96. Epub 2021 Jun 18.

National Clinical Research Center for Mental Disorders, Department of Psychiatry, China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China. Electronic address:

Objective: This study aimed to investigate the role of Brain-derived neurotrophic factor (BDNF) in clinical and cognitive outcomes in medication-naïve patients with Bipolar type II disorder (BD II) and Major depressive disorder (MDD).

Methods: 45 outpatients with BD II, 40 outpatients with MDD and 40 healthy controls (HCs) were recruited, and sociodemographic and clinical data were collected. Their BDNF serum levels were measured and analyzed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Results: BDNF levels were significantly lower in BD II patients than in MDD patients and HCs (p = 0.001). BD II and MDD patients had similar cognitive performance deficits shown on Attention (p = 0.001), Delayed memory (p = 0.001), and RBANS total score (p = 0.001). BDNF levels were positively associated with Visuospatial / constructional and Stroop color-word in BD II group, and with language in MDD group. The area under the curve (AUC) of the ROC analysis in BD II vs. MDD was 0.664, therefore, BDNF levels could not distinguish BD II from MDD.

Conclusion: Our study showed the decreased serum BDNF in MDD and BD II patients, suggesting BDNF may be involved in the pathophysiology of MDD and BD II. BDNF and cognitive deficits are both of low efficiency in distinguishing BD II from MDD. Decrease of BDNF may potentially indicate cognitive dysfunction in BD II and MDD patients with a current depressive episode.
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http://dx.doi.org/10.1016/j.jad.2021.06.018DOI Listing
June 2021

Estimation of in-scanner head pose changes during structural MRI using a convolutional neural network trained on eye tracker video.

Magn Reson Imaging 2021 Sep 18;81:101-108. Epub 2021 Jun 18.

Comprehensive Epilepsy Center, Department of Neurology, NYU Grossman School of Medicine, New York, USA.

Introduction: In-scanner head motion is a common cause of reduced image quality in neuroimaging, and causes systematic brain-wide changes in cortical thickness and volumetric estimates derived from structural MRI scans. There are few widely available methods for measuring head motion during structural MRI. Here, we train a deep learning predictive model to estimate changes in head pose using video obtained from an in-scanner eye tracker during an EPI-BOLD acquisition with participants undertaking deliberate in-scanner head movements. The predictive model was used to estimate head pose changes during structural MRI scans, and correlated with cortical thickness and subcortical volume estimates.

Methods: 21 healthy controls (age 32 ± 13 years, 11 female) were studied. Participants carried out a series of stereotyped prompted in-scanner head motions during acquisition of an EPI-BOLD sequence with simultaneous recording of eye tracker video. Motion-affected and motion-free whole brain T1-weighted MRI were also obtained. Image coregistration was used to estimate changes in head pose over the duration of the EPI-BOLD scan, and used to train a predictive model to estimate head pose changes from the video data. Model performance was quantified by assessing the coefficient of determination (R). We evaluated the utility of our technique by assessing the relationship between video-based head pose changes during structural MRI and (i) vertex-wise cortical thickness and (ii) subcortical volume estimates.

Results: Video-based head pose estimates were significantly correlated with ground truth head pose changes estimated from EPI-BOLD imaging in a hold-out dataset. We observed a general brain-wide overall reduction in cortical thickness with increased head motion, with some isolated regions showing increased cortical thickness estimates with increased motion. Subcortical volumes were generally reduced in motion affected scans.

Conclusions: We trained a predictive model to estimate changes in head pose during structural MRI scans using in-scanner eye tracker video. The method is independent of individual image acquisition parameters and does not require markers to be to be fixed to the patient, suggesting it may be well suited to clinical imaging and research environments. Head pose changes estimated using our approach can be used as covariates for morphometric image analyses to improve the neurobiological validity of structural imaging studies of brain development and disease.
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http://dx.doi.org/10.1016/j.mri.2021.06.010DOI Listing
September 2021

Fusion proteins of biologic agents in the treatment of rheumatoid arthritis (RA): A network meta-analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26350

Department of Epidemiology and Biostatistics.

Background: To evaluate the efficacy of fusion proteins biologics (Etanercept (ETN), Anakinra (ANA), and Abatacept) combinations in the treatment of rheumatoid arthritis (RA) using network meta-analysis to rank those according to their performance medicines. The performance of these processes is ranked according to the results of the analysis and an explanatory study of the possible results is carried out.

Methods: Multiple databases including PubMed, EMBASE, and Cochrane Library were used to identify applicable articles and collect relevant data to analyze using STATA (14.0) software. The literature included in this study was divided into a combination of a placebo, methotrexate (MTX), and an observation group (1 of the 3 drugs). The last search date was December 12, 2019.

Results: A total of 19 eligible randomized controlled trials of fusion proteins biologics were identified, a total of 1109 papers were included, and the results showed that the ETN + MTX had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking curve of 91.6, was significantly superior (P < .05). Patients who had received ETN or ETN + MTX or ANA had effective compared with patients who had received placebo (95% CI 1.28%-8.47%; 1.92%-19.18%; 1.06%-10.45%).

Conclusions: 1. The combination of ETN and MTX had the highest probability of optimal treatment compared to other drugs and 2. ENT, ENT + MTX, and ANA were effective in the treatment of RA compared to placebo.
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http://dx.doi.org/10.1097/MD.0000000000026350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213327PMC
June 2021

Analyzing and Validating the Prognostic Value of a TNF-Related Signature in Kidney Renal Clear Cell Carcinoma.

Front Mol Biosci 2021 28;8:689037. Epub 2021 May 28.

The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

Kidney renal clear cell carcinoma (KIRC) has the highest incidence rate in renal cell carcinoma (RCC). Although bioinformatics is widely used in cancer, few reliable biomarkers of KIRC have been found. Therefore, continued efforts are required to elucidate the potential mechanism of the biogenesis and progression of KIRC. We evaluated the expression of tumor necrosis factor (TNF) family genes in KIRC, and constructed a prognostic signature. We validated the signature by another database and explored the relationship between the signature and progression of KIRC. We assessed the prognostic value, immune infiltration, and tumor mutation burden (TMB) of the signature in KIRC. We selected four key genes (, , , and ) to construct the TNF-related signature. We divided the KIRC patients into high- and low-risk groups based on the signature. Patients with higher risk scores had shorter overall survival and worse prognosis. With another database, we validated the value of the signature. The signature was considered as an independent risk factor. A higher level of risk score was relevant to higher level of immune infiltration, especially T regulatory cells, CD8 T cells, and macrophages. The signature was also associated with TMB scores, and it may have an effect on assessing the efficacy of immunotherapy. This is the first TNF-family-related signature of KIRC and we demonstrated its effectiveness. It played a significant role in predicting the prognosis of patients with KIRC. It also has the potential to become a powerful tool in guiding the immunotherapy of KIRC patients in clinical practice.
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http://dx.doi.org/10.3389/fmolb.2021.689037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194470PMC
May 2021

OPG/TRAIL ratio as a predictive biomarker of mortality in patients with type A acute aortic dissection.

Nat Commun 2021 06 7;12(1):3401. Epub 2021 Jun 7.

Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Following hospital discharge, patients with type A acute aortic dissection (TA-AAD) may present an increase in mortality risk. However, little is known about specific biomarkers associated with post-discharge survival, and there is a paucity of prognostic markers associated with TA-AAD. Here, we identify nine candidate proteins specific for patietns with TA-AAD in a cross-sectional dataset by unbiased protein screening and in-depth bioinformatic analyses. In addition, we explore their association with short-term and long-term mortality in a derivation cohort of patients with TA-AAD, including an internal (n = 300) and external (n = 236) dataset. An elevated osteoprotegerin (OPG)/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) ratio was the strongest predictor of overall, 30-day, post-30-day mortality in both datasets and was confirmed to be a strong predictor of mortality in an independent validation cohort (n = 400). Based on OPG/TRAIL ratio-guided risk stratification, patients at high risk (>33) had a higher 1-year mortality (55.6% vs. 4.3%; 68.2% vs. 2.6%) than patients at low risk (<4) in both cohorts. In Conclusion, we show that an elevated OPG/TRAIL ratio is associated with a significant increase in short-term and long-term mortality in patients with TA-AAD.
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http://dx.doi.org/10.1038/s41467-021-23787-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185077PMC
June 2021

[Retracted] MicroRNA‑195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer.

Int J Mol Med 2021 Jul 3;48(1). Epub 2021 Jun 3.

Department of Gynecology, Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell assay data in the article (featured in Figs. 3B and 7B) were strikingly similar to data appearing in different form in other articles by different authors at different research institutes that had already been published elsewhere at the time of the present article's submission. Furthermore, the scratch wound assay data in Fig. 7A of the above paper were strikingly similar to data published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 42: 779-788, 2018; DOI: 10.3892/ijmm.2018.3660].
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http://dx.doi.org/10.3892/ijmm.2021.4973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175067PMC
July 2021

Active-Site Models of Cas9 in DNA Cleavage State.

Front Mol Biosci 2021 21;8:653262. Epub 2021 Apr 21.

State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, Ministry of Education Engineering Research Centre of Gene Technology, School of Life Sciences, Fudan University, Shanghai, China.

CRISPR-Cas9 is a powerful tool for target genome editing in living cells. Significant advances have been made to understand how this system cleaves target DNA. HNH is a nuclease domain, which shares structural similarity with the HNH endonuclease characterzied by a beta-beta-alpha-metal fold. Therefore, based on one- and two-metal-ion mechanisms, homology modeling and molecular dynamics (MD) simulation are suitable tools for building an atomic model of Cas9 in the DNA cleavage state. Here, by modeling and MD, we presented an atomic model of SpCas9-sgRNA-DNA complex with the cleavage state. This model shows that the HNH and RuvC conformations resemble their DNA cleavage state where the active-sites in the complex coordinate with DNA, Mg ions, and water. Among them, residues D10, E762, H983, and D986 locate at the first shell of the RuvC active-site and interact with the ions directly, residues H982 or/and H985 are general (Lewis) bases, and the coordinated water is located at the positions for nucleophilic attack of the scissile phosphate. Meanwhile, this catalytic model led us to engineer a new SpCas9 variant (SpCas9-H982A + H983D) with reduced off-target effects. Thus, our study provided new mechanistic insights into the CRISPR-Cas9 system in the DNA cleavage state and offered useful guidance for engineering new CRISPR-Cas9 editing systems with improved specificity.
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http://dx.doi.org/10.3389/fmolb.2021.653262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112549PMC
April 2021

Molecular engineering of piezoelectricity in collagen-mimicking peptide assemblies.

Nat Commun 2021 05 11;12(1):2634. Epub 2021 May 11.

George S. Wise Faculty of Life Sciences, Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Ramat Aviv, Israel.

Realization of a self-assembled, nontoxic and eco-friendly piezoelectric device with high-performance, sensitivity and reliability is highly desirable to complement conventional inorganic and polymer based materials. Hierarchically organized natural materials such as collagen have long been posited to exhibit electromechanical properties that could potentially be amplified via molecular engineering to produce technologically relevant piezoelectricity. Here, by using a simple, minimalistic, building block of collagen, we fabricate a peptide-based piezoelectric generator utilising a radically different helical arrangement of Phe-Phe-derived peptide, Pro-Phe-Phe and Hyp-Phe-Phe, based only on proteinogenic amino acids. The simple addition of a hydroxyl group increases the expected piezoelectric response by an order of magnitude (d = 27 pm V). The value is highest predicted to date in short natural peptides. We demonstrate tripeptide-based power generator that produces stable max current >50 nA and potential >1.2 V. Our results provide a promising device demonstration of computationally-guided molecular engineering of piezoelectricity in peptide nanotechnology.
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http://dx.doi.org/10.1038/s41467-021-22895-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113556PMC
May 2021

Gold Cluster Capped with a BCL-2 Antagonistic Peptide Exerts Synergistic Antitumor Activity in Chronic Lymphocytic Leukemia Cells.

ACS Appl Mater Interfaces 2021 May 4;13(18):21108-21118. Epub 2021 May 4.

Department of Chemistry and Biology, Faculty of Environment and Life Science, Beijing University of Technology, Beijing 100124, China.

Chronic lymphocytic leukemia (CLL) is still incurable by conventional chemotherapy due to the resistance to apoptosis. We have previously found that a peptide-capped gold cluster (AuSv) can target on the aberrant oxidative stress in CLL cells to specially inhibit thioredoxin reductase (TrxR) activity, resulting in significant apoptosis. However, the required doses of the gold cluster for inducing apoptosis are high, restricting its potential for further applications. Notably, the most recent studies suggested that CLL cells overexpressed antiapoptotic BCL-2 protein to prevent chemotherapy-induced apoptosis, indicating that BCL-2 could be a promising target for CLL therapy. Regrettably, the nonmitochondrial-targeted AuSv has little effect on BCL-2. In this study, we successfully screened a modified BADBH3 peptide (B1P) that could antagonize BCL-2 protein in CLL cells. We found that B1P could effectively sensitize MEC-1 cells to a subliminal dose of AuSv. To simplify the treatment regimen, we directly fabricated a gold cluster capped with the B1P peptides by one-step synthesis to integrate the BCL-2 antagonistic activity into the gold the cluster, named BGC. We already found that low doses of BGC could significantly induce more apoptosis in MEC-1 cells than equivalent doses of the AuSv cluster or B1P peptide alone. Mechanistically, in addition to the inherent inhibitory effect of gold clusters on TrxR activity, BGC could bind to BCL-2 on mitochondria and activate the BCL-2 family-mediated mitochondrial apoptosis cascade more effectively. These results demonstrated that antagonizing the overexpressed BCL-2 in CLL cells, together with inhibiting TrxR simultaneously by a single gold cluster, is a promising strategy for the treatment of CLL cells. This study will provide a paradigm and reference for the development of functionalized gold clusters with rationally designed peptides, and opens up a new opportunity for the treatment of CLL in clinical settings.
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http://dx.doi.org/10.1021/acsami.1c05550DOI Listing
May 2021

Comparative transcriptome analyses shed light on carotenoid production and plastid development in melon fruit.

Hortic Res 2021 May 1;8(1):112. Epub 2021 May 1.

Robert W. Holley Center for Agriculture and Health, USDA-Agricultural Research Service, Cornell University, Ithaca, NY, 14853, USA.

Carotenoids, such as β-carotene, accumulate in chromoplasts of various fleshy fruits, awarding them with colors, aromas, and nutrients. The Orange (CmOr) gene controls β-carotene accumulation in melon fruit by posttranslationally enhancing carotenogenesis and repressing β-carotene turnover in chromoplasts. Carotenoid isomerase (CRTISO) isomerizes yellow prolycopene into red lycopene, a prerequisite for further metabolism into β-carotene. We comparatively analyzed the developing fruit transcriptomes of orange-colored melon and its two isogenic EMS-induced mutants, low-β (Cmor) and yofi (Cmcrtiso). The Cmor mutation in low-β caused a major transcriptomic change in the mature fruit. In contrast, the Cmcrtiso mutation in yofi significantly changed the transcriptome only in early fruit developmental stages. These findings indicate that melon fruit transcriptome is primarily altered by changes in carotenoid metabolic flux and plastid conversion, but minimally by carotenoid composition in the ripe fruit. Clustering of the differentially expressed genes into functional groups revealed an association between fruit carotenoid metabolic flux with the maintenance of the photosynthetic apparatus in fruit chloroplasts. Moreover, large numbers of thylakoid localized photosynthetic genes were differentially expressed in low-β. CmOR family proteins were found to physically interact with light-harvesting chlorophyll a-b binding proteins, suggesting a new role of CmOR for chloroplast maintenance in melon fruit. This study brings more insights into the cellular and metabolic processes associated with fruit carotenoid accumulation in melon fruit and reveals a new maintenance mechanism of the photosynthetic apparatus for plastid development.
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http://dx.doi.org/10.1038/s41438-021-00547-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087762PMC
May 2021

Investigation on sleep quality in Chinese medical staff during the COVID-19 pandemic.

Psychol Health Med 2021 Apr 27:1-7. Epub 2021 Apr 27.

School of Public Health, Wannan Medical College, Wuhu, Anhui, China.

The aims of this study were to evaluate the situation of sleep quality among Chinese medical staff during the coronavirus disease 2019 (COVID-19) pandemic. We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality among medical staff from 8 May 2020 to 22 May 2020 in People's Republic of China. A total of 101 (25%) participants were poor sleepers, while 303 (75%) were good sleepers, as defined by PSQI. The PSQI scores were higher in high age, married, master/doctor, nurse, and frequent night shifts groups when compared with those in middle and low age, unmarried and divorced/widowed, bachelor or below, clinician and other job, low frequency night shifts, respectively (all < 0.01). Multiple linear regression analysis showed that higher PSQI score was positively associated with higher educational background, age, and more frequent night shifts (all < 0.001). Sleep quality of medical staff should be improved, especially for high age, married, master/doctor, nurse, and frequent night shifts groups.
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http://dx.doi.org/10.1080/13548506.2021.1922722DOI Listing
April 2021

Increased Production of Short-Chain Fatty Acids in Microbacteria Fermentation Treated by Fullerenols.

J Nanosci Nanotechnol 2021 10;21(10):5352-5362

CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science (CAS), Beijing 100049, China.

Fullerenol nanoparticles were found to significantly modulate the gut microbiota and selectively enrich the short-chain fatty acids (SCFAs) production by adjusting the gut microbacteria in mice models. In this research, we screened the from seven strains and investigated the interactions and mechanism between the and fullerenol NPs fermentation. The results shows that fullerenol NPs increased the amounts of acetate and butyrate of without significant bacteria growth in the complete medium. The activities of the butyryl-CoA: acetate CoA transferase (BUT), which are the main pathway to produce butyrate, were reduced while the activities of the butyrate kinase (BUK) were enhanced simultaneously. Surprisingly, fullerenol NPs promoted the growth of and in low glucose medium, but they could not be direct carbon source in the culture. Moreover, when cocultured with and the bifidobacterial strains in fullerenols, the biomass and acetate production of were markedly increased while butyrate was decreased significantly.
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http://dx.doi.org/10.1166/jnn.2021.19341DOI Listing
October 2021

One-stage versus two-stage management for acute cholecystitis associated with common bile duct stones: a retrospective cohort study.

Surg Endosc 2021 Mar 31. Epub 2021 Mar 31.

Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China.

Background: Both one-stage [laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE)] and two-stage [endoscopic retrograde cholangiopancreatography (ERCP) followed by sequential LC] approaches are effective treatment for concomitant common bile duct (CBD) stones and gallstone. Although many studies compared one-stage with two-stage surgical approach for cholecysto-choledocholithiasis, there are very few studies compared the two management strategies for acute cholecystitis (AC) associated with CBD stones.

Methods: Between January 2014 and December 2019, patients with concomitant AC and CBD stones proposed to early surgery were retrospectively studied. The patients were scheduled to undergo either the one-stage [LCBDE and LC (LCBDE+LC) were undertaken at the same operation] or two-stage [preoperative ERCP for CBD stone clearance was followed by LC 1-3 days later (pre-ERCP+LC)] procedure. The success rate of complete stone clearance, procedure-related complication, hospital stay, hospitalization charges and later biliary complications were compared between the two groups.

Results: Sixty patients were included in the study, 28 in the one-stage group and 32 in the two-stage group. There was no significant difference in the success rate of complete stone clearance (96.4% vs. 93.8%, P = 1.000), complication rate (10.7% vs. 9.4%, P = 1.000), incidence of pancreatitis (0 vs. 6.3%, P = 0.494) or length of hospital stay (12 ± 5 vs. 11 ± 4 days, P = 0.393) between the two groups.

Conclusion: For patients with concomitant AC and choledocholithiasis proposed to early surgery, both the one-stage (LCBDE+LC) and two-stage (pre-ERCP+LC) approaches were acceptable and broadly comparable in achieving clearance of CBD stones.
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http://dx.doi.org/10.1007/s00464-021-08349-6DOI Listing
March 2021

Serum C1q concentration is associated with disease activity in Chinese Takayasu arteritis patients: A case-control study.

Health Sci Rep 2021 Jun 23;4(2):e252. Epub 2021 Mar 23.

Department of Clinical Laboratory Beijing Anzhen Hospital, Capital Medical University Beijing China.

Background: C1q is a crucial component of the classical complement pathway. This study is the first to assess the association between disease activity and serum levels of C1q in Chinese Takayasu arteritis (TA) patients.

Methods: Serum C1q levels in 198 TA patients and 154 healthy controls were assessed, and the relationship between serum C1q levels and indices of TA disease activity was analyzed. Moreover, we examined the correlation between serum C1q levels and two traditional inflammatory biomarkers; erythrocyte sedimentation rate (ESR) and hypersensitive CRP (hs-CRP).

Results: Serum C1q levels were increased in TA patients compared with healthy controls ( = .008). TA patients with active disease had higher levels of serum C1q than patients who had inactive disease ( < .0001). In addition, treatment-naïve patients had higher serum C1q levels than those who had been treated with corticosteroids or at least one immunosuppressant ( = .001). Furthermore, a positive correlation between serum C1q levels and traditional inflammatory biomarkers in TA patients was found. The role of C1q in assessing disease activity was studied, and the area under the receiver operating characteristic curve (AUC) of C1q for predicting active disease was 0.752, and a serum cutoff value of 167.15 mg/L C1q maximized the ability of disease activity assessment, with a sensitivity/specificity of 77.80%/64.90%. When the three indicators (C1q, ESR, and hs-CRP) were combined, the AUC increased to 0.845, and the sensitivity to 84.40%.

Conclusions: The serum C1q is associated with the disease activity of TA and the combination of three indicators (C1q, ESR, and hs-CRP) increases the sensitivity of disease activity assessment.
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http://dx.doi.org/10.1002/hsr2.252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986161PMC
June 2021

The mechanism for brassinosteroids suppressing climacteric fruit ripening.

Plant Physiol 2021 Apr;185(4):1875-1893

Key Laboratory of Fruit Postharvest Biology, Liaoning Province, College of Horticulture, Shenyang Agricultural University, Shenyang 110866, China.

The plant hormone ethylene is important for the ripening of climacteric fruit, such as pear (Pyrus ussuriensis), and the brassinosteroid (BR) class of phytohormones affects ethylene biosynthesis during ripening via an unknown molecular mechanism. Here, we observed that exogenous BR treatment suppressed ethylene production and delayed fruit ripening, whereas treatment with a BR biosynthesis inhibitor promoted ethylene production and accelerated fruit ripening in pear, suggesting BR is a ripening suppressor. The expression of the transcription factor BRASSINAZOLE-RESISTANT 1PuBZR1 was enhanced by BR treatment during pear fruit ripening. PuBZR1 interacted with PuACO1, which converts 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene, and suppressed its activity. BR-activated PuBZR1 bound to the promoters of PuACO1 and of PuACS1a, which encodes ACC synthase, and directly suppressed their transcription. Moreover, PuBZR1 suppressed the expression of transcription factor PuERF2 by binding its promoter, and PuERF2 bound to the promoters of PuACO1 and PuACS1a. We concluded that PuBZR1 indirectly suppresses the transcription of PuACO1 and PuACS1a through its regulation of PuERF2. Ethylene production and expression profiles of corresponding apple (Malus domestica) homologs showed similar changes following epibrassinolide treatment. Together, these results suggest that BR-activated BZR1 suppresses ACO1 activity and the expression of ACO1 and ACS1, thereby reducing ethylene production and suppressing fruit ripening. This likely represents a conserved mechanism by which BR suppresses ethylene biosynthesis during climacteric fruit ripening.
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http://dx.doi.org/10.1093/plphys/kiab013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133653PMC
April 2021

Ifenprodil Improves Long-Term Neurologic Deficits Through Antagonizing Glutamate-Induced Excitotoxicity After Experimental Subarachnoid Hemorrhage.

Transl Stroke Res 2021 Mar 12. Epub 2021 Mar 12.

Department of Neurology, Second Affiliated Hospital; Key Laboratory of Cerebral Microcirculation, Shandong First Medical University & Shandong Academy of Medical Sciences, Yingsheng East Road No.2, Taian, 271016, China.

Excessive glutamate leading to excitotoxicity worsens brain damage after SAH and contributes to long-term neurological deficits. The drug ifenprodil is a non-competitive antagonist of GluN1-GluN2B N-methyl-d-aspartate (NMDA) receptor, which mediates excitotoxic damage in vitro and in vivo. Here, we show that cerebrospinal fluid (CSF) glutamate level within 48 h was significantly elevated in aSAH patients who later developed poor outcome. In rat SAH model, ifenprodil can improve long-term sensorimotor and spatial learning deficits. Ifenprodil attenuates experimental SAH-induced neuronal death of basal cortex and hippocampal CA1 area, cellular and mitochondrial Ca overload of basal cortex, blood-brain barrier (BBB) damage, and cerebral edema of early brain injury. Using in vitro models, ifenprodil declines the high-concentration glutamate-mediated intracellular Ca increase and cell apoptosis in primary cortical neurons, reduces the high-concentration glutamate-elevated endothelial permeability in human brain microvascular endothelial cell (HBMEC). Altogether, our results suggest ifenprodil improves long-term neurologic deficits through antagonizing glutamate-induced excitotoxicity.
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http://dx.doi.org/10.1007/s12975-021-00906-4DOI Listing
March 2021

Green Conversion of Saponins to Diosgenin in an Alcoholysis System Catalyzed by Solid Acid Derived from Phosphorus Tailings.

ACS Omega 2021 Mar 19;6(8):5423-5435. Epub 2021 Feb 19.

College of Chemistry and Environmental Technology, Wuhan Institute of Technology, Wuhan 430073, China.

This work proposed to prepare solid acid from phosphorus tailings and successfully convert Dioscorea zingiberensis C.H. Wright (DZW) into diosgenin from the perspective of solid waste resource reuse and clean production. The results showed that SiO-SOH solid acid could catalyze the production of diosgenin from total saponins under solvothermal reaction conditions. In addition, the parameters of a single factor, such as the amount of SiO-SOH, solvent volume, reaction temperature, and reaction time, were optimized to confirm the optimal range of reaction conditions, and the optimal process conditions were determined by the response surface method. The yield of diosgenin was 2.45 ± 0.17% under the optimum conditions, and the yield of diosgenin was increased by 12.90% compared with the traditional acid hydrolysis process. Except the relatively higher catalytic activity, the alcoholysis approach for the production of diosgenin has no waste liquid to discharge. The products were analyzed by high-performance liquid chromatography-mass spectrometry, and the pathway to convert total saponins into diosgenin under SiO-SOH has been proposed. Moreover, the adopted catalyst can be prepared with very low cost from phosphorus tailings. Considering the obvious superiorities, the alcoholysis approach in this work could be a promising strategy for green production of diosgenin as well as a possible utilization pathway of phosphorus tailings.
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http://dx.doi.org/10.1021/acsomega.0c05627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931428PMC
March 2021

Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular Carcinoma.

Genomics Proteomics Bioinformatics 2021 Mar 1. Epub 2021 Mar 1.

Department of Pathology and Institute of Oncology, School of Basic Medical Sciences of Fujian Medical University, Fuzhou 350004, China. Electronic address:

Early detection and intervention are key strategies to reduce mortality, increase long-term survival and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ) quantitative proteomic strategy was used to study the secretome in conditioned medium from HCC cancerous tissues, surrounding noncancerous and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients than that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence (TTR) and overall survival (OS). Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition (EMT) pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis and provided a valuable resource of HCC secretome for investigating serological biomarkers.
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http://dx.doi.org/10.1016/j.gpb.2020.09.005DOI Listing
March 2021

Consensus module analysis of abdominal fat deposition across multiple broiler lines.

Authors:
Hui Yuan Jun Lu

BMC Genomics 2021 Feb 10;22(1):115. Epub 2021 Feb 10.

College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, Heilongjiang, China.

Background: Despite several RNA-Seq and microarray studies on differentially expressed genes (DEGs) between high- and low-abdominal fat deposition in different broiler lines, to our knowledge, gene coexpression analysis across multiple broiler lines has rarely been reported. Here, we constructed a consensus gene coexpression network focused on identifying consensus gene coexpression modules associated with abdominal fat deposition across multiple broiler lines using two public RNA-Seq datasets (GSE42980 and GSE49121).

Results: In the consensus gene coexpression network, we identified eight consensus modules significantly correlated with abdominal fat deposition across four broiler lines using the consensus module analysis function in the weighted gene coexpression network analysis (WGCNA) package. The eight consensus modules were moderately to strongly preserved in the abdominal fat RNA-Seq dataset of another broiler line (SRP058295). Furthermore, we identified 5462 DEGs between high- and low-abdominal fat lines (FL and LL) (GSE42980) and 6904 DEGs between high- and low-growth (HG and LG) (GSE49121), including 1828 overlapping DEGs with similar expression profiles in both datasets, which were clustered into eight consensus modules. Pyruvate metabolism, fatty acid metabolism, and steroid biosynthesis were significantly enriched in the green, yellow, and medium purple 3 consensus modules. The PPAR signaling pathway and adipocytokine signaling pathway were significantly enriched in the green and purple consensus modules. Autophagy, mitophagy, and lysosome were significantly enriched in the medium purple 3 and yellow consensus modules.

Conclusion: Based on lipid metabolism pathways enriched in eight consensus modules and the overexpression of numerous lipogenic genes in both FL vs. LL and HG vs. LG, we hypothesize that more fatty acids, triacylglycerols (TAGs), and cholesterol might be synthesized in broilers with high abdominal fat than in broilers with low abdominal fat. According to autophagy, mitophagy, and lysosome enrichment in eight consensus modules, we inferred that autophagy might participate in broiler abdominal fat deposition. Altogether, these studies suggest eight consensus modules associated with abdominal fat deposition in broilers. Our study also provides an idea for investigating the molecular mechanism of abdominal fat deposition across multiple broiler lines.
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http://dx.doi.org/10.1186/s12864-021-07423-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876793PMC
February 2021

Using water-based drilling cuttings from shale gas development to manufacture sintered bricks: a case study in the southern Sichuan Basin, China.

Environ Sci Pollut Res Int 2021 Jun 8;28(23):29379-29393. Epub 2021 Feb 8.

College of Chemistry and Chemical Engineering, Southwest Petroleum University, No. 8 Xin Du Avenue, Xin Du District, Chengdu, 610500, China.

Large amounts of water-based drilling cuttings (WDC) would be generated during the drilling of shale gas wells, which would occupy land resources and pose significant threat to soil and groundwater environment. The aim of this study was to assess the feasibility of using WDC as a replacement of natural clay to prepare sintered bricks. To determine the optimum preparation condition, the weight loss on ignition, bulk density, water absorption, and compressive strength of the samples were tested. Meanwhile, the environmental performance of the final products was evaluated and micro-analysis was conducted via X-ray diffraction and scanning electron microscopy. The results showed that using WDC to manufacture sintered bricks was technically feasible, but the physical mechanical performance would significantly decrease with the increase of the replacement ratio because of the presence of less silica and excessive calcium. The addition of waste glass and fly ash could promote the generation of molten glassy phase and form the crystal particle bonding structure, which would contribute to the physical-mechanical performance of WDC sintered bricks. Some mineral components in raw materials decomposed and formed minerals with better thermal stability during the sintering process. Under the optimum preparation conditions (mass ratio of WDC: waste glass: fly ash at 40:20:40, sintering temperature at 900 °C, and insulation time at 2 h), the physical-mechanical and environmental performance of WDC sintered bricks could meet the requirements of corresponding Chinese standards and ASTM standards. Thus, in this study, an effective solution to recycle WDC from shale gas development is provided.
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http://dx.doi.org/10.1007/s11356-021-12847-4DOI Listing
June 2021

Association of dementia with immunoglobulin G N-glycans in a Chinese Han Population.

NPJ Aging Mech Dis 2021 Feb 4;7(1). Epub 2021 Feb 4.

Department of Epidemiology and Health Statistics, School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, 100069, China.

Immunoglobulin G (IgG) functionality can drastically change from anti- to proinflammatory by alterations in the IgG N-glycan patterns. Our previous studies have demonstrated that IgG N-glycans associated with the risk factors of dementia, such as aging, dyslipidemia, type 2 diabetes mellitus, hypertension, and ischemic stroke. Therefore, the aim is to investigate whether the effects of IgG N-glycan profiles on dementia exists in a Chinese Han population. A case-control study, including 81 patients with dementia, 81 age- and gender-matched controls with normal cognitive functioning (NC) and 108 non-matched controls with mild cognitive impairment (MCI) was performed. Plasma IgG N-glycans were separated by ultra-performance liquid chromatography. Fourteen glycan peaks reflecting decreased of sialylation and core fucosylation, and increased bisecting N-acetylglucosamine (GlcNAc) N-glycan structures were of statistically significant differences between dementia and NC groups after controlling for confounders (p < 0.05; q < 0.05). Similarly, the differences for these 14 initial glycans were statistically significant between AD and NC groups after adjusting for the effects of confounders (p < 0.05; q < 0.05). The area under the receiver operating curve (AUC) value of the model consisting of GP8, GP9, and GP14 was determined to distinguish dementia from NC group as 0.876 [95% confidence interval (CI): 0.815-0.923] and distinguish AD from NC group as 0.887 (95% CI: 0.819-0.936). Patients with dementia were of an elevated proinflammatory activity via the significant changes of IgG glycome. Therefore, IgG N-glycans might contribute to be potential novel biomarkers for the neurodegenerative process risk assessment of dementia.
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http://dx.doi.org/10.1038/s41514-021-00055-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862610PMC
February 2021

Comparison of Liver Biomarkers in 288 COVID-19 Patients: A Mono-Centric Study in the Early Phase of Pandemic.

Front Med (Lausanne) 2020 15;7:584888. Epub 2021 Jan 15.

Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Recent reports have indicated that hepatic dysfunction occurred in a proportion of patients with coronavirus disease 2019 (COVID-19). We aimed to compare and describe the liver biomarkers in different subtypes of COVID-19 patients. This study enrolled 288 COVID-19 patients in Huangshi Hospital of Traditional Chinese Medicine. All patients were divided into ordinary, severe, and critical groups according to the . Demographic, clinical characteristics and liver biomarkers were compared among the three groups. During hospitalization, AST, TBiL, and ALP levels in ordinary and severe patients fluctuated within the normal range with a rising trend in critical patients except AST. ALT and GGT levels fluctuated within the normal range showing an upward trend, while LDH levels in the critical group exceeded the normal range. Prealbumin showed an upward trend, especially in the severe group. At discharge, AST and LDH levels in ordinary and severe groups were lower than their baselines but increased in the critical group. In contrast to albumin, TBiL levels were increased in ordinary and critical groups while decreased in the severe group. The stratified analysis revealed factors affecting liver function in critical cases included highest temperature ≥38.0°C, age ≥60 and symptom of hypoxemia. COVID-19 can cause severe hepatic dysfunction in critical patients, requiring early monitoring and intervention. LDH, ALP, GGT, TBiL, prealbumin, and albumin may be helpful for evaluating and predicting disease prognosis due to their correlation with disease severity in COVID-19.
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http://dx.doi.org/10.3389/fmed.2020.584888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843802PMC
January 2021

Endogenous Auxin Content Contributes to Larger Size of Apple Fruit.

Front Plant Sci 2020 3;11:592540. Epub 2020 Dec 3.

Key Laboratory of Fruit Postharvest Biology, College of Horticulture, Shenyang Agricultural University, Shenyang, China.

Fruit size is an important economic trait that is controlled by multiple genes. However, the regulatory mechanism for fruit size remains poorly understood. A bud sport variety of "Longfeng" (LF) apple () was identified and named "Grand Longfeng" (GLF). The fruit size of GLF is larger than that of LF, and both varieties are diploid. We found that the cell size in GLF fruit was larger than that of LF. Then, we compared the fruit transcriptomes of the two varieties using RNA-Seq technology. A total of 1166 differentially expressed genes (DEGs) were detected between GLF and LF fruits. The KEGG analysis revealed that the phytohormone pathway was the most enriched, in which most of the DEGs were related to auxin signaling. Moreover, the endogenous auxin levels of GLF fruit were higher than those of LF. The expressions of auxin synthetic genes, including and , were higher in GLF fruit than LF. Collectively, our findings suggest that auxin plays an important role in fruit size development.
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http://dx.doi.org/10.3389/fpls.2020.592540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841441PMC
December 2020

ABCA8-mediated efflux of taurocholic acid contributes to gemcitabine insensitivity in human pancreatic cancer via the S1PR2-ERK pathway.

Cell Death Discov 2021 Jan 11;7(1). Epub 2021 Jan 11.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The development of resistance to anticancer drugs is believed to cause chemotherapy failure in pancreatic cancer (PC). The efflux of anticancer drugs mediated by ATP-binding cassette (ABC) transporters is a widely accepted mechanism for chemoresistance, but for ABCA subfamily members, which are characterized by their ability to transport lipids and cholesterol, its role in chemoresistance remains unknown. Here we found that the expression of ABCA8, a member of ABCA subfamily transporters, was significantly increased in human PC cells after gemcitabine (GEM) treatment, as well as in established GEM-resistant (Gem-R) PC cells. Importantly, ABCA8 knockdown reversed the chemoresistance phenotype of Gem-R cells, whereas ABCA8 overexpression significantly decreased the sensitivity of human PC cells to GEM, both in vitro and in vivo, demonstrating an important role of ABCA8 in regulating chemosensitivity. Moreover, our results showed that treatment with taurocholic acid (TCA), an endogenous substrate of ABCA8, also induced GEM insensitivity in PC cells. We further demonstrated that ABCA8 mediates the efflux of TCA out of PC cells, and that extracellular TCA activates extracellular signal-regulated kinase (ERK) signaling via the sphingosine 1-phosphate receptor 2 (S1PR2), which is responsible for ABCA8-induced GEM ineffectiveness. Together, these findings reveal a novel TCA-related mechanism of ABCA subfamily transporter-mediated chemoresistance that goes beyond the role of a drug pump and suggest ABCA8 or the TCA-S1RP2-ERK pathway as potential targets for improving the effectiveness of and overcoming the resistance to chemotherapy in PC.
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http://dx.doi.org/10.1038/s41420-020-00390-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801517PMC
January 2021

Inflammatory microenvironment of fibrotic liver promotes hepatocellular carcinoma growth, metastasis and sorafenib resistance through STAT3 activation.

J Cell Mol Med 2021 Feb 7;25(3):1568-1582. Epub 2021 Jan 7.

Department of Abdominal Surgery, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

The pro-inflammatory and pro-fibrotic liver microenvironment facilitates hepatocarcinogenesis. However, the effects and mechanisms by which the hepatic fibroinflammatory microenvironment modulates intrahepatic hepatocellular carcinoma (HCC) progression and its response to systematic therapy remain largely unexplored. We established a syngeneic orthotopic HCC mouse model with a series of persistent liver injury induced by CCl gavage, which mimic the dynamic effect of hepatic pathology microenvironment on intrahepatic HCC growth and metastasis. Non-invasive bioluminescence imaging was applied to follow tumour progression over time. The effect of the liver microenvironment modulated by hepatic injury on sorafenib resistance was investigated in vivo and in vitro. We found that the persistent liver injury facilitated HCC growth and metastasis, which was positively correlated with the degree of liver inflammation rather than the extent of liver fibrosis. The inflammatory cytokines in liver tissue were clearly increased after liver injury. The two indicated cytokines, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), both promoted intrahepatic HCC progression via STAT3 activation. In addition, the hepatic inflammatory microenvironment contributed to sorafenib resistance through the anti-apoptotic protein mediated by STAT3, and STAT3 inhibitor S3I-201 significantly improved sorafenib efficacy impaired by liver inflammation. Clinically, the increased inflammation of liver tissues was accompanied with the up-regulated STAT3 activation in HCC. Above all, we concluded that the hepatic inflammatory microenvironment promotes intrahepatic HCC growth, metastasis and sorafenib resistance through activation of STAT3.
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http://dx.doi.org/10.1111/jcmm.16256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875922PMC
February 2021