Publications by authors named "Yu Tian"

1,054 Publications

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ROS‑associated mechanism of different concentrations of pinacidil postconditioning in the rat cardiac Nrf2‑ARE signaling pathway.

Mol Med Rep 2021 Jun 13;23(6). Epub 2021 Apr 13.

Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.

Previous studies have confirmed that 50 mol/l pinacidil postconditioning (PPC) activates the nuclear factor‑E2 related factor 2 (Nrf2)‑antioxidant responsive element (ARE) pathway, which protects the myocardium from ischemia‑reperfusion (IR) injury; however, whether this is associated with reactive oxygen species (ROS) generation remains unclear. In the present study, a Langendorff rat model of isolated myocardial IR was established to investigate the mechanism of PPC at different concentrations, as well as the association between the rat myocardial Nrf2‑ARE signaling pathway and ROS. A total of 48 rats were randomly divided into the following six groups (n=8 per group): i) Normal; ii) IR iii) 10 mol/l PPC (P10); iv) 30 mol/l PPC (P30); v) 50 mol/l PPC (P50); and vi) N‑(2‑mercaptopropionyl)‑glycine (MPG; a ROS scavenger) + 50 mol/l pinacidil (P50 + MPG). At the end of reperfusion (T3), compared with the IR group, the P10, P30 and P50 groups exhibited improved cardiac function, such as left ventricular development pressure, heart rate, left ventricular end‑diastolic pressure, +dp/dtmax, myocardial cell ultrastructure and mitochondrial Flameng score. Furthermore, the P10 and P50 groups demonstrated the weakest and most marked improvements, respectively. Additionally, in the P10, P30 and P50 groups, the residual ROS content at the end of reperfusion was highly negatively correlated with relative expression levels of Nrf2 gene and protein. Higher pinacidil concentration was associated with higher ROS generation at 5 min post‑reperfusion (T2), although this was significantly lower compared with the IR group, as well as with increased expression levels of antioxidant proteins and phase II detoxification enzymes downstream of the Nrf2 and Nrf2‑ARE pathways. This result was associated with a stronger ability to scavenge ROS during reperfusion, leading to lower levels of ROS at the end of reperfusion (T3) and less myocardial damage. The optimal myocardial protective effect was achieved by 50 mmol/l pinacidil. However, cardiac function of the P50 + MPG group was significantly decreased, ultrastructure of cardiomyocytes was significantly impaired and the relative expression levels of genes and proteins in the Nrf2‑ARE pathway were decreased. The aforementioned results confirmed that different PPC concentrations promoted early generation of ROS and activated the Nrf2‑ARE signaling pathway following reperfusion, regulated expression levels of downstream antioxidant proteins and alleviated myocardial IR injury in rats. Treatment with 50 mmol/l pinacidil resulted in the best myocardial protection.
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http://dx.doi.org/10.3892/mmr.2021.12072DOI Listing
June 2021

Iminostilbene, a novel small-molecule modulator of PKM2, suppresses macrophage inflammation in myocardial ischemia-reperfusion injury.

J Adv Res 2021 Mar 9;29:83-94. Epub 2020 Sep 9.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

Introduction: Inflammation is a key factor in myocardial ischemia/reperfusion (MI/R) injury. Targeting leucocyte-mediated inflammation is an important strategy for MI/R therapy. Iminostilbene (ISB), a simple dibenzoazepine small molecule compound, has a strong anti-neurodegenerative effect. However, no study has shown the cardioprotective effect of ISB.

Objectives: This study aimed to investigate the role of ISB against MI/R injury and identify its molecular target.

Methods: To verify the cardiac protection of ISB and , we performed rat MI/R surgery and subjected inflammatory modeling of macrophages. In terms of molecular mechanisms, we designed and synthesized a small molecular probe of ISB and employed it on the click chemistry-activity-based protein profiling technique to fish for ISB targets in macrophages. To identify the target, we applied the competitive inhibition assay, surface-plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay.

Results: , ISB showed robust anti-myocardial injury activity by improving cardiac function, reducing myocardial infarction, and inhibiting macrophage-mediated inflammation. , ISB strongly inhibited the transcription and the expression levels of inflammatory cytokines in macrophages. The pyruvate kinase isozyme type M2 (PKM2) was identified as the potential target of ISB through proteomic analysis and the competitive assay was performed for specific binding verification. Further thermodynamic and kinetic experiments showed that ISB was bound to PKM2 in a dose-dependent manner. Moreover, in terms of the biological function of ISB on PKM2, ISB reduced the expression of PKM2, thereby reducing the expression of HIF1α and the phosphorylation of STAT3.

Conclusion: This study for the first time demonstrated that ISB targeted PKM2 to reduce macrophage inflammation thereby significantly alleviating MI/R injury.
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http://dx.doi.org/10.1016/j.jare.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020153PMC
March 2021

Rapid, simultaneous detection of mycotoxins with smartphone recognition-based immune microspheres.

Anal Bioanal Chem 2021 Apr 7. Epub 2021 Apr 7.

School of Life Sciences, Tianjin University, Tianjin, 300072, China.

How to achieve simultaneous and rapid detection of various mycotoxins in food has important practical significance in the field of food processing and safety. In this paper, a smartphone immunoassay system based on hydrogel microspheres has been constructed to quickly detect two mycotoxins at the same time. The rapid detection system was reflected in the following three processes: (1) rapid separation of free matter after direct competition reaction based on hydrogel solid-phase carrier particles; (2) rapid detection process based on efficient catalytic function of enzymes; (3) fast capture and analysis of images based on smartphone software. Ochratoxin A (OTA) and zearalenone (ZEN) are secondary toxic metabolites of fungi that can contaminate a wide range of foods and feeds. OTA and ZEN were used as detection model molecules to verify the feasibility of the intelligent rapid detection system. The entire detection process was within 30 min, and the results were analyzed in only 10 s. Detection limits of mycotoxins OTA and ZEN are 0.7711 ng L and 1.0391 ng L. The recoveries of both mycotoxins ranged from 76.72 to 122.05%. This study provides a universal rapid detection method for on-site application of large-scale food security testing. Schematic diagram of the construction of the smartphone detection system: The system is divided into three parts: detection, image capture and analysis, and result.
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http://dx.doi.org/10.1007/s00216-021-03316-5DOI Listing
April 2021

Method of Tumor Pathological Micronecrosis Quantification via Deep Learning from Label Fuzzy Proportions.

IEEE J Biomed Health Inform 2021 Apr 6;PP. Epub 2021 Apr 6.

The presence of necrosis is associated with tumor progression and patient outcomes in many cancers, but existing analyses rarely adopt quantitative methods because the manual quantification of histopathological features is too expensive. We aim to accurately identify necrotic regions on hematoxylin and eosin (HE)stained slides and to calculate the ratio of necrosis with minimal annotations on the images. An adaptive method named Learning from Label Fuzzy Proportions (LLFP) was introduced to histopathological image analysis. Two datasets of liver cancer HE slides were collected to verify the feasibility of the method by training on the internal set using cross validation and performing validation on the external set, along with ensemble learning to improve performance. The models from cross validation performed relatively stably in identifying necrosis, with a Concordance Index of the Slide Necrosis Score (CISNS) of 0.91650.0089 in the internal test set. The integration model improved the CISNS to 0.9341 and achieved a CISNS of 0.8278 on the external set. There were significant differences in survival (p=0.0060) between the three groups divided according to the calculated necrosis ratio. The proposed method can build an integration model good at distinguishing necrosis and capable of clinical assistance as an automatic tool to stratify patients with different risks or as a cluster tool for the quantification of histopathological features. We presented a method effective for identifying histopathological features and suggested that the extent of necrosis, especially micronecrosis, in liver cancer is related to patient outcomes.
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http://dx.doi.org/10.1109/JBHI.2021.3071276DOI Listing
April 2021

Multicenter privacy-preserving Cox analysis based on homomorphic encryption.

IEEE J Biomed Health Inform 2021 Apr 6;PP. Epub 2021 Apr 6.

The Cox proportional hazards model is one of the most widely used methods for analyzing survival data. Data from multiple data providers are required to improve the generalizability and confidence of the results of Cox analysis; however, such data sharing may result in leakage of sensitive information, leading to financial fraud, social discrimination or unauthorized data abuse. Some privacy-preserving Cox regression protocols have been proposed in past years, but they lack either security or functionality. In this paper, we propose a privacy-preserving Cox regression protocol for multiple data providers and researchers. The proposed protocol allows researchers to train models on horizontally or vertically partitioned datasets while providing privacy protection for both the sensitive data and the trained models. Our protocol utilizes threshold homomorphic encryption to guarantee security. Experimental results demonstrate that with the proposed protocol, Cox regression model training over 9 variables in a dataset of 113,035 samples takes approximately 44 min, and the trained model is almost the same as that obtained with the original nonsecure Cox regression protocol; therefore, our protocol is a potential candidate for practical real-world applications in multicenter medical research.
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http://dx.doi.org/10.1109/JBHI.2021.3071270DOI Listing
April 2021

Selenium yeast promoted the Se accumulation, nutrient quality and antioxidant system of cabbage ( var. L.).

Plant Signal Behav 2021 Apr 5:1907042. Epub 2021 Apr 5.

College of Horticulture and Gardening, Yangtze University, Jingzhou, China.

The application of Se yeast as a Se source to cultivate Se-rich cabbage has a significant effect on cabbage growth and quality indices. Results showed that total plant weight, head weight, and head size in cabbage were notably increased by 48.4%, 88.3%, and 25.4% under 16 mg/kg Se yeast treatment, respectively. Compare with the control, a high proportion of 3874% of Se accumulation in cabbage head was also detected in 16 mg/kg Se yeast treatment. Selenocystine (SeCys) and Methyl-selenocysteine (MeSeCys) were the main Se speciations in the cabbage head. Application of 8 mg/kg Se yeast improved cabbage quality and antioxidant system indices, including free amino acid, soluble sugar, ascorbic acid, phenolic acid, glucosinolates, and SOD activity, which had 81.6%, 46.5%, 34.9%, 12.3%, 44.8%, 25.2% higher than that of the control, respectively. In summary, considering 8 mg/kg Se yeast as the appropriate level of Se enrichment during cabbage cultivation. These findings enhanced our understanding of the effects of Se yeast on the growth and quality of cabbage and provided new insights into Se-enrichment vegetable cultivation.
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http://dx.doi.org/10.1080/15592324.2021.1907042DOI Listing
April 2021

Three-dimensional pulsed continuous arterial spin labeling and intravoxel incoherent motion imaging of nasopharyngeal carcinoma: correlations with Ki-67 proliferation status.

Quant Imaging Med Surg 2021 Apr;11(4):1394-1405

Pathology Department, The First People's Hospital of Foshan, Foshan, China.

Background: Recurrence and distant metastasis are still the main problems affecting the long-term prognosis of nasopharyngeal carcinoma (NPC) patients, and may be related to the Ki-67 proliferation status. We therefore explored the potential correlation between Ki-67 proliferation status in NPC with the parameters derived from two imaging techniques: three-dimensional pulsed continuous arterial spin labeling (3D pCASL) and intravoxel incoherent motion (IVIM).

Methods: Thirty-six patients with pathologically confirmed NPC were included, and the Ki-67 labeling index (LI) was measured by immunohistochemistry. All patients underwent plain and contrast-enhanced magnetic resonance imaging (MRI), IVIM, and 3D pCASL examination. The mean, maximum, and minimum of blood flow (BF), minimum of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) parameters were all measured, and Spearman's correlation analysis was performed to evaluate the relationships between these parameters and the Ki-67 LI. According to the Ki-67 values, the patients were divided into two groups: high (>50%) and low (≤50%). The rank-sum test (Mann-Whitney U test) was then used to compare the differences in quantitative parameters between the high and low Ki-67 groups.

Results: Ki-67 LI was positively correlated with BF and BF (r=0.415 and 0.425). D* and D* did have positive correlation with Ki-67, but this was not significant (P=0.082 and 0.072). BF was significantly different between the high and low Ki-67 groups (P=0.028).

Conclusions: 3D pCASL and IVIM are noninvasive functional MR perfusion imaging techniques that can evaluate perfusion information and perfusion parameters. Our study suggests that 3D pCASL is more effective than IVIM for assessing the proliferation status of NPC, which is beneficial for evaluating the prognosis of patients. Furthermore, BF is the best biomarker for distinguishing high from low Ki-67 levels.
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http://dx.doi.org/10.21037/qims-20-349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930700PMC
April 2021

Prediction Scores for Any-Stage and Stage-3 Acute Kidney Injury After Adult Cardiac Surgery in a Chinese Population.

J Cardiothorac Vasc Anesth 2021 Feb 22. Epub 2021 Feb 22.

Department of Cardiopulmonary Bypass, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Objectives: This study was performed to internally derive and then validate risk score systems using preoperative and intraoperative variables to predict the occurrence of any-stage (stage 1, 2, 3) and stage-3 acute kidney injury (AKI) within seven days of cardiac surgery.

Design: Single-center, retrospective, observational study.

Setting: Single, large, tertiary care center.

Participants: Adult patients undergoing open cardiac surgery between January 1, 2012, and January 1, 2019.

Measurements And Main Results: The clinical data were divided into the following two groups: a derivation cohort (n = 43,799) and a validation cohort (n = 14,600). AKI was defined using the Kidney Disease: Improving Global Outcomes criteria. Multivariate logistic regression analysis was used to develop the prediction models. The overall prevalence of any-stage AKI and stage-3 AKI after cardiac surgery were 34.3% and 1.7%, respectively. The discriminatory ability of the any-stage AKI prediction model measured with the area under the curve (AUC) was acceptable (AUC = 0.69, 95% confidence interval 0.68-0.69), and the calibration measured with the Hosmer-Lemeshow test was good (p = 0.95). The AUC for the stage-3 AKI prediction model was 0.84 (95% confidence interval 0.83-0.85), and the Hosmer-Lemeshow test also indicated a good calibration (p = 0.73).

Conclusions: This research study, which used preoperative and intraoperative variables, derived and internally validated two predictive scoring systems for any-stage AKI and stage-3 AKI as defined by modified Kidney Disease: Improving Global Outcomes criteria using a very large cohort of Chinese cardiac surgical patients.
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http://dx.doi.org/10.1053/j.jvca.2021.02.047DOI Listing
February 2021

Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice.

Nutrients 2021 Mar 24;13(4). Epub 2021 Mar 24.

Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.

Ghrelin is a major appetite-stimulating neuropeptide found in circulation. While its role in increasing food intake is well known, its role in affecting taste perception, if any, remains unclear. In this study, we investigated the role of the growth hormone secretagogue receptor's (GHS-R; a ghrelin receptor) activity in the peripheral taste system using feeding studies and conditioned taste aversion assays by comparing wild-type and GHS-R-knockout models. Using transgenic mice expressing enhanced green fluorescent protein (GFP), we demonstrated GHS-R expression in the taste system in relation phospholipase C ß2 isotype (PLCβ2; type II taste cell marker)- and glutamate decarboxylase type 67 (GAD67; type III taste cell marker)-expressing cells using immunohistochemistry. We observed high levels of co-localization between PLCβ2 and GHS-R within the taste system, while GHS-R rarely co-localized in GAD67-expressing cells. Additionally, following 6 weeks of 60% high-fat diet, female mice exhibited reduced responsiveness to linoleic acid (LA) compared to their wild-type (WT) counterparts, while no such differences were observed in male and WT mice. Overall, our results are consistent with the interpretation that ghrelin in the taste system is involved in the complex sensing and recognition of fat compounds. Ghrelin-GHS-R signaling may play a critical role in the recognition of fatty acids in female mice, and this differential regulation may contribute to their distinct ingestive behaviors.
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http://dx.doi.org/10.3390/nu13041045DOI Listing
March 2021

Cyclodextrins as Supramolecular Recognition Systems: Applications in the Fabrication of Electrochemical Sensors.

Materials (Basel) 2021 Mar 28;14(7). Epub 2021 Mar 28.

Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.

Supramolecular chemistry, although focused mainly on noncovalent intermolecular and intramolecular interactions, which are considerably weaker than covalent interactions, can be employed to fabricate sensors with a remarkable affinity for a target analyte. In this review the development of cyclodextrin-based electrochemical sensors is described and discussed. Following a short introduction to the general properties of cyclodextrins and their ability to form inclusion complexes, the cyclodextrin-based sensors are introduced. This includes the combination of cyclodextrins with reduced graphene oxide, carbon nanotubes, conducting polymers, enzymes and aptamers, and electropolymerized cyclodextrin films. The applications of these materials as chiral recognition agents and biosensors and in the electrochemical detection of environmental contaminants, biomolecules and amino acids, drugs and flavonoids are reviewed and compared. Based on the papers reviewed, it is clear that cyclodextrins are promising molecular recognition agents in the creation of electrochemical sensors, chiral sensors, and biosensors. Moreover, they have been combined with a host of materials to enhance the detection of the target analytes. Nevertheless, challenges remain, including the development of more robust methods for the integration of cyclodextrins into the sensing unit.
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http://dx.doi.org/10.3390/ma14071668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036645PMC
March 2021

BBB-crossing adeno-associated virus vector: An excellent gene delivery tool for CNS disease treatment.

J Control Release 2021 Mar 26;333:129-138. Epub 2021 Mar 26.

School of Medicine, Yangzhou University, Yangzhou 225600, China; Department of Oncology, Yangzhou Traditional Chinese Medical Hospital, Yangzhou 225600, China. Electronic address:

The presence of the blood-brain barrier (BBB) remains a challenge in the treatment of central nervous system (CNS) diseases, as it hinders the infiltration of many therapeutic drugs into the brain parenchyma. Therefore, developing efficacious pharmacological agents that can traverse the BBB is crucial for optimal treatment of diseases of the CNS such as neurodegenerative conditions and brain tumors. Adeno-associated virus (AAV), one of the most promising gene therapy vectors, has been shown to cross the BBB safely and is non-pathogenic in nature and therefore has been utilized for numerous diseases of the CNS. Along with the development of protein engineering techniques such as directed evolution including DNA shuffling, a great number of BBB-crossing AAVs have been developed, that could be systemically injected for therapeutic benefit. In this review, we discuss several feasible approaches to improve transportation of therapeutic agents to the CNS. We also discuss the advantages of using BBB-crossing AAVs, their role as a gene delivery agent and highlight the different types of BBB-AAV vectors that have been developed in order to provide a greater insight into how they can be used in diseases of the CNS.
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http://dx.doi.org/10.1016/j.jconrel.2021.03.029DOI Listing
March 2021

Role of extracellular polymeric substances on nutrients storage and transfer in algal-bacteria symbiosis sludge system treating wastewater.

Bioresour Technol 2021 Mar 19;331:125010. Epub 2021 Mar 19.

Shaanxi Key Laboratory of Environmental Engineering, Key Laboratory of Northwest Water Resource, Environment and Ecology, Ministry of Education, School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China; International Science & Technology Cooperation Center for Urban Alternative Water Resources Development, Xi'an 710055, China.

This study reported the role and significance of extracellular polymeric substances (EPSs) on nutrients storage and transfer in an algal-bacteria symbiosis sludge (ABSS) system for wastewater treatment, and the novel algae-based sequencing batch suspended biofilm reactor (A-SBSBR, Ra) was selected as model of ABSS system. Results showed that compared to conventional SBSBR, the EPS of Ra performed better storage for NO-N, NO-N, total phosphorus and PO -P, with increase ratios of 43.7%, 36.0%, 34.1% and 14.7% in sludge phase and 174.0%, 147.4%, 150.4% and 122.0% in biofilm phase, respectively. The analysis of mechanisms demonstrated that microalgae active transport and uptake for divalent cations could enhance their local concentrations around ABS flocs and partially neutralized negative charge of EPSs, and more anions related to nutrients were absorbed in EPSs. Moreover, O produced by microalgae photosynthesis enhanced bacteria activity and improved the production of EPSs in both sludge and biofilm phases.
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http://dx.doi.org/10.1016/j.biortech.2021.125010DOI Listing
March 2021

Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol.

Front Neurosci 2021 9;15:636901. Epub 2021 Mar 9.

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

Propofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminergic nervous system of the ventral tegmental area (VTA) and the noradrenergic system of locus coeruleus (LC) play a crucial role in hedonic experiences, which are putative sites for mediating the hedonic effects of propofol. In the present study, rat hedonic response scale and place conditioning paradigm were employed to examine the euphoric effects of propofol. GCaMP-based (AVV-hSyn-GCaMP6s) fiber photometry calcium imaging was used to monitor the real-time neuronal activity in VTA and LC area in rats exhibiting propofol-induced euphoric behaviors. Then DREADDs (designer receptors exclusively activated by designer drugs) modulation using rAAV-hSyn-hM4D(Gi)-EGFP was performed to confirm the neuronal substrate that mediates the euphoric effects of propofol. The score of hedonic facial responses was significantly increased in the 4 mg/kg group compared with that of the 0 mg/kg group. The locomotor activity in the propofol-paired compartment was significantly increased at the 4 mg/kg dose compared with that of the saline-paired group. When compared with the 0 mg/kg group, the place preference increased in the 4 mg/kg group. Administration of 4 mg/kg of propofol triggers reliable increases in GcaMP fluorescence. However, in the VTA GcaMP-expressing rats, administration of 4 mg/kg of propofol did not induce any change of GcaMP signals. The facial score and the place preference, which increased by 4 mg/kg propofol were abolished by chemogenetic inhibition of the neuronal activity in the LC area. Our results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol.
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http://dx.doi.org/10.3389/fnins.2021.636901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985178PMC
March 2021

Ferritin disorder in the plasma and hippocampus associated with major depressive disorder.

Biochem Biophys Res Commun 2021 Mar 22;553:114-118. Epub 2021 Mar 22.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing, 400016, China. Electronic address:

Major depressive disorder (MDD) is a debilitating mental illness that can cause significant emotional disturbances and severe socioeconomic burdens. Rodent and nonhuman primate-based depression models have been studied, such as brain-derived neurotrophic factor (BDNF) and monoamine acid disorder hypotheses, as well as peripheral microbiota disturbances causing MDD; however, the pathogenesis is still largely unknown. This study aims to explore the relationship between ferritin and MDD. First, alterations in ferritin, including ferritin light chain (FTL) and ferritin heavy chain (FTH), in MDD patient plasma compared with healthy control (HC) plasma were detected using ELISA. Then, serum ferritin expression in cLPS-depressed mice was measured by ELISA. The existence of FTH in the hippocampus was validated by immunofluorescence, and the change in FTH levels in the hippocampus of mice injected with cLPS was detected by western blotting. FTL levels in MDD patients were decreased compared with those in HCs. In cLPS-depressed mice, serum ferritin was not different from that in the control group, while the expression of FTH in the hippocampus was significantly reduced in depressed mice. Our findings demonstrate the alteration of ferritin expression in MDD and provide new insight into the pathogenesis of MDD.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.059DOI Listing
March 2021

Effect of basal forebrain somatostatin and parvalbumin neurons in propofol and isoflurane anesthesia.

CNS Neurosci Ther 2021 Mar 25. Epub 2021 Mar 25.

Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, China.

Aims: The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABA ) and parvalbumin-positive (GABA ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.

Methods: Based on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BF and BF neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared.

Results: Activation of BF GABA neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABA -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABA neurons.

Conclusions: Our results suggested that BF GABA neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABA neurons appeared to have little effect.
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http://dx.doi.org/10.1111/cns.13635DOI Listing
March 2021

Single-cell transcriptome dissection of the toxic impact of Di (2-ethylhexyl) phthalate on primordial follicle assembly.

Theranostics 2021 5;11(10):4992-5009. Epub 2021 Mar 5.

College of Life Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao 266109, China.

Accumulated evidence indicates that environmental plasticizers are a threat to human and animal fertility. Di (2-ethylhexyl) phthalate (DEHP), a plasticizer to which humans are exposed daily, can trigger reproductive toxicity by acting as an endocrine-disrupting chemical. In mammals, the female primordial follicle pool forms the lifetime available ovarian reserve, which does not undergo regeneration once it is established during the fetal and neonatal period. It is therefore critical to examine the toxicity of DEHP regarding the establishment of the ovarian reserve as it has not been well investigated. The ovarian cells of postnatal pups, following maternal DEHP exposure, were prepared for single cell-RNA sequencing, and the effects of DEHP on primordial follicle formation were revealed using gene differential expression analysis and single-cell developmental trajectory. In addition, further biochemical experiments, including immunohistochemical staining, apoptosis detection, and Western blotting, were performed to verify the dataset results. Using single-cell RNA sequencing, we revealed the gene expression dynamics of female germ cells and granulosa cells following exposure to DEHP in mice. Regarding germ cells: DEHP impeded the progression of follicle assembly and interfered with their developmental status, while key genes such as , and others, strongly evidenced the reduction. As for granulosa cells: DEHP likely inhibited their proliferative activity, and activated the regulation of cell death. Furthermore, the interaction between ovarian cells mediated by transforming growth factor-beta signaling, was disrupted by DEHP exposure, since the expression of GDF9, BMPR1A, and SMAD3 was affected. In addition, DNA damage and apoptosis were elevated in germ cells and/or somatic cells. These findings offer substantial novel insights into the reproductive toxicity of DEHP exposure during murine germ cell cyst breakdown and primordial follicle formation. These results may enhance the understanding of DEHP exposure on reproductive health.
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http://dx.doi.org/10.7150/thno.55006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978297PMC
March 2021

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Front Mol Neurosci 2021 4;14:628996. Epub 2021 Mar 4.

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings , we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.
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http://dx.doi.org/10.3389/fnmol.2021.628996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969819PMC
March 2021

Chemical formation and source apportionment of PM at an urban site at the southern foot of the Taihang mountains.

J Environ Sci (China) 2021 May 24;103:20-32. Epub 2020 Oct 24.

Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The region along the Taihang Mountains in the North China Plain (NCP) is characterized by serious fine particle pollution. To clarify the formation mechanism and controlling factors, an observational study was conducted to investigate the physical and chemical properties of the fine particulate matter in Jiaozuo city, China. Mass concentrations of the water-soluble ions (WSIs) in PM and gaseous pollutant precursors were measured on an hourly basis from December 1, 2017, to February 27, 2018. The positive matrix factorization (PMF) method and the FLEXible PARTicle (FLEXPART) model were employed to identify the sources of PM. The results showed that the average mass concentration of PM was 111 μg/m during the observation period. Among the major WSIs, sulfate, nitrate, and ammonium (SNA) constituted 62% of the total PM mass, and NO ranked the highest with an average contribution of 24.6%. NH was abundant in most cases in Jiaozuo. According to chemical balance analysis, SO, NO, and Cl might be present in the form of (NH)SO, NHNO, NHCl, and KCl. The liquid-phase oxidation of SO and NO was severe during the haze period. The relative humidity and pH were the key factors influencing SO formation. We found that NO mainly stemmed from homogeneous gas-phase reactions in the daytime and originated from the hydrolysis of NO in the nighttime, which was inconsistent with previous studies. The PMF model identified five sources of PM: secondary origin (37.8%), vehicular emissions (34.7%), biomass burning (11.5%), coal combustion (9.4%), and crustal dust (6.6%).
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http://dx.doi.org/10.1016/j.jes.2020.10.004DOI Listing
May 2021

How to design comfortable open spaces for the elderly? Implications of their thermal perceptions in an urban park.

Sci Total Environ 2021 May 8;768:144985. Epub 2021 Jan 8.

School of Architecture, Tsinghua University, Beijing 100084, China; Key Laboratory of Eco Planning & Green Building, Ministry of Education, Tsinghua University, China.

Elderly residents are prominent users of urban parks and comfortable open spaces in parks have been shown to improve their physical health and mental well-being. In this study, the thermal perceptions (thermal sensation, thermal comfort and thermal acceptability) of elderly visitors to an urban park in Xi'an, China was investigated using meteorological measurements, questionnaire surveys and activity records. Physiological equivalent temperature (PET) was used to determine thermal benchmarks. Spatial-temporal distributions of the elderly in open spaces were recorded and relationships among elderly residents' thermal perceptions, their age and chronic disease were analyzed. Finally, optimal design strategies for open spaces suitable for the elderly were proposed based on meteorological characteristics, elderly residents' attendance patterns and their thermal perceptions. Results showed that: 1) globe temperature (T) and air temperature (T) were the primary meteorological factors that influenced elderly residents' thermal sensation while clothing insulation and activity intensity were negatively correlated with their thermal sensation. 2) Attendance was significantly affected by the outdoor microclimate, space functionality and facilities in spaces. The elderly mainly participated in dynamic activities and social interaction. 3) The neutral PET (NPET) was 13.2 °C, with NPET range (NPETR) of 3.1-23.2 °C. The 90% thermal acceptable PET ranged between 10.9 and 25.9 °C, and the preferred PET was 14.4 °C. Compared with the ISO7730 standard, the predicted percentage of dissatisfied (PPD) elderly park users was lower than users of indoor spaces when -1 ≤ MTSV ≤ + 1, indicating that the elderly preferred to conduct activities outside when the environment was comfortable. Additionally, NPET for the elderly with respiratory disease was higher than those with cardiovascular diseases and diabetes. 4) Optimal design strategies for open spaces were proposed for elderly residents based on their physical, physiological and psychological preferences.
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http://dx.doi.org/10.1016/j.scitotenv.2021.144985DOI Listing
May 2021

Effects of Abrasive Particles on Liquid Superlubricity and Mechanisms for Their Removal.

Langmuir 2021 Mar 18;37(12):3628-3636. Epub 2021 Mar 18.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.

Liquid superlubricity results in a near-frictionless lubrication state, which can greatly reduce friction and wear under aqueous conditions. However, during the running-in process, a large number of abrasive particles are generated, and because these may lead to a breakdown in superlubricity performance, they should be effectively removed. In this paper, the morphology, size, and composition of abrasive particles were verified using scanning electron microscopy with energy-dispersive X-ray spectroscopy, and their influence on liquid superlubricity was explored through friction tests. Subsequently, different solvents were used to remove the abrasive particles, and the optimal cleaning process was determined by macroscopic tribo-tests and microscopic analysis. Finally, droplet-spreading experiments and a force-curve analysis were carried out to understand the abrasive-particle removal mechanism by different solvents. We found that SiO was the main component in the abrasive particles, and micron-sized SiO particles resulted in random "wave peaks" in the coefficient of friction and, thus, the superlubricity. Absolute ethanol + ultrapure water was determined to be the optimal solvent for effectively removing abrasive particles from friction-pair surfaces and helped the lubricant in exhibiting an ultralow friction coefficient for long periods of time. We proposed a "wedge" and "wrap" model to explain the abrasive-particle removal mechanism of different solvents. The SiO removal mechanism outlined in this study can be applied under aqueous conditions to improve the stability and durability of liquid superlubricity in practical engineering applications.
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http://dx.doi.org/10.1021/acs.langmuir.0c03607DOI Listing
March 2021

The disappearance of IPO in myocardium of diabetes mellitus rats is associated with the increase of succinate dehydrogenase-flavin protein.

BMC Cardiovasc Disord 2021 Mar 17;21(1):142. Epub 2021 Mar 17.

Zunyi Medical University, Zunyi, People's Republic of China.

Background: The aim of the present study was to investigate whether the disappearance of ischemic post-processing (IPO) in the myocardium of diabetes mellitus (DM) is associated with the increase of succinate dehydrogenase-flavin protein (SDHA).

Methods: A total of 50 Sprague Dawley rats, weighing 300-400 g, were divided into 5 groups according to the random number table method, each with 10 rats. After DM rats were fed a high-fat and -sugar diet for 4 weeks, they were injected with Streptozotocin to establish the diabetic rat model. Normal rats were fed the same regular diet for the same number of weeks. Next, the above rats were taken to establish a cardiopulmonary bypass (CPB) model. Intraperitoneal glucose tolerance test (IPGTT) and oral glucose tolerance test (OGTT) were used to detect whether the DM rat model was established successfully. Taking blood from the femoral artery to collect the blood-gas analysis indicators, and judged whether the CPB model is established. After perfusion was performed according to the experimental strategy, the area of myocardial infarction (MI), and serum creatine kinase isoenzyme (CK-MB) and cardiac troponin (CTnI) levels were measured. Finally, the relative mRNA and protein expression of SDHA was detected.

Results: The OGTT and IPGTT suggested that the DM rat model was successfully established. The arterial blood gas analysis indicated that the CPB model was successfully established. As compared with the N group, the heart function of the IR group was significantly reduced, the levels of myocardial enzyme markers, the area of MI, as well as the relative mRNA and protein expression of SDHA, were all increased. As compared with the IR group, the CK-MB and CTnI levels in the IPO group, the MI area, relative mRNA and protein expression of SDHA decreased. As compared with the IPO group, the myocardial enzyme content in the DM + IPO group, the MI area and the relative mRNA and protein expression of SDHA increased. As compared with the DM + IPO group, in the DM + IPO + dme group, the myocardial enzyme content, area of MI and relative mRNA and protein expression were all decreased.

Conclusion: IPO can inhibit the expression of SDHA, reduce MIRI and exert a cardioprotective effect in the normal rats. However, the protective effect of IPO disappears in the diabetic rats. The inhibitor dme combined with IPO can increase the expression of SDHA and restore the protective effect of IPO in DM myocardia.
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http://dx.doi.org/10.1186/s12872-021-01949-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968298PMC
March 2021

Wound Dressing Hydrogel of Polysaccharide-Polyacrylamide Composite: A Facile Transformation of Marine Blooming into Biomedical Material.

ACS Appl Mater Interfaces 2021 Mar 17;13(12):14530-14542. Epub 2021 Mar 17.

College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, Qingdao 266003, China.

Great endeavors have been dedicated to the development of wound dressing materials. However, there is still a demand for developing a wound dressing hydrogel that integrates natural macromolecules without requiring extra chemical modifications, so as to enable a facile transformation and practical application in wound healing. Herein, a composite hydrogel was prepared with water-soluble polysaccharides from (PEP) cross-linked with boric acid and polyacrylamide cross-linked via polymerization (PAM) using a one-pot method. The dual-network of this hydrogel enabled it to have an ultratough mechanical strength. Moreover, interfacial characterizations reflected that the hydrogen bonds and dynamic hydroxyl-borate bonds contributed to the self-healing ability of the PEP-PAM hydrogel, and the surface groups on the hydrogel allowed for tissue adhesiveness and natural antioxidant properties. Additionally, human epidermal growth factor-loaded PEP-PAM hydrogel promoted cell proliferation and migration in vitro and significantly accelerated wound healing in vivo on model rats. These progresses suggested a prospect for the PEP-PAM hydrogel as an effective and easily available wound dressing material. Remarkably, this work showcases that a wound dressing hydrogel can be facially developed by using natural polysaccharides as a one component and offers a new route for the high-value utilization of disastrous marine blooming biomass by transforming it into a biomedical material.
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http://dx.doi.org/10.1021/acsami.0c21543DOI Listing
March 2021

A Nanometer-Sized Graphite/Boron-Doped Diamond Electrochemical Sensor for Sensitive Detection of Acetaminophen.

ACS Omega 2021 Mar 22;6(9):6326-6334. Epub 2021 Feb 22.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, P. R. China.

A boron-doped diamond (BDD) has been widely used as an outstanding electrode for constructing high-performance electrochemical biosensors. In this paper, we fabricated a novel electrode combined of nanometer-sized graphite-BDD film (NG-BDD) by chemical vapor deposition. The nanometer-sized graphite (NG) is formed on the (111) facet of BDD via converting an sp diamond structure to an sp graphitic phase at high temperature in boron-rich ambient. The electrode was characterized by means of scanning electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. This NG-BDD was performed as an electrode of electrochemical biosensor to detect trace acetaminophen (APAP) accurately. Cyclic voltammetry and differential normal pulse voltammetry are used to investigate the overall performance of the electrochemical device. The sensor has a linear electrochemical response to APAP in the concentration range of 0.02-50 μM, and the detection limit is estimated to be as low as 5 nM. The research has resulted in a solution of constructing a reusable NG-BDD sensor to detect APAP with stability and show potential in extensive application.
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http://dx.doi.org/10.1021/acsomega.0c06141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948231PMC
March 2021

Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/β-catenin signaling pathway in taxol-resistant human lung adenocarcinoma.

Transl Lung Cancer Res 2021 Feb;10(2):1007-1019

Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance.

Methods: Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of β-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3α/β was evaluated by western blot and IHC.

Results: Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxol-resistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelial-mesenchymal transition (EMT) through repression of the p70S6K/GSK3/β-catenin signaling pathway.

Conclusions: Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/β-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.
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http://dx.doi.org/10.21037/tlcr-21-145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947389PMC
February 2021

Anticancer effect of sodium metavanadate on murine breast cancer both in vitro and in vivo.

Biometals 2021 Mar 10. Epub 2021 Mar 10.

Department of Occupational Health and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.

Sodium metavanadate (NaVO) exhibits important physiological effects including insulin-like, chemoprevention and anticancer activity. However, the effects of NaVO on breast cancer and underlying mechanisms are still unclear. In this study, our results revealed that NaVO was able to inhibit proliferation of murine breast cancer cells 4T1 with IC value of 8.19 μM and 1.92 μM at 24 h and 48 h, respectively. The mechanisms underlying the inhibition activity were that NaVO could increase reactive oxygen species (ROS) level in a concentration-dependent way, arrest cells at G2/M phase, diminish the mitochondrial membrane potential (MMP), finally promote the progress of apoptosis. Furthermore, NaVO also exhibited a dose-dependent anticancer activity in breast cancer-bearing mice that led to the shrinkage of tumor volume (about 50%), lower microvessel density, less propagating cells and more apoptotic cells in vivo, as compared to the saline group. Therefore, NaVO may act as a potential chemotherapeutic agent in breast cancer treatment.
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http://dx.doi.org/10.1007/s10534-021-00295-zDOI Listing
March 2021

Deep Semisupervised Multitask Learning Model and its Interpretability for Survival Analysis.

IEEE J Biomed Health Inform 2021 Mar 9;PP. Epub 2021 Mar 9.

Survival analysis is a commonly used method in the medical field to analyze and predict the time of events. In medicine, this approach plays a key role in determining the course of treatment, developing new drugs, and improving hospital procedures. Most of the existing work in this area has addressed the problem by making strong assumptions about the underlying stochastic process. However, these assumptions are usually violated in the real-world data. This paper proposed a semisupervised multitask learning (SSMTL) method based on deep learning for survival analysis with or without competing risks. SSMTL transforms the survival analysis problem into a multitask learning problem that includes semisupervised learning and multipoint survival probability prediction. The distribution of survival times and the relationship between covariates and outcomes were modeled directly without any assumptions. Semisupervised loss and ranking loss are used to deal with censored data and the prior knowledge of the nonincreasing trend of the survival probability. Additionally, the importance of prognostic factors is determined, and the time-dependent and nonlinear effects of these factors on survival outcomes are visualized. The prediction performance of SSMTL is better than that of previous models in settings with or without competing risks, and the effects of predictors are successfully described. This study is of great significance for the exploration and application of deep learning methods involving medical structured data and provides an effective deep-learning-based method for survival analysis with complex-structured clinical data.
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http://dx.doi.org/10.1109/JBHI.2021.3064696DOI Listing
March 2021

Ultra-High-Resolution IonStar Strategy Enhancing Accuracy and Precision of MS1-Based Proteomics and an Extensive Comparison with State-of-the-Art SWATH-MS in Large-Cohort Quantification.

Anal Chem 2021 03 9;93(11):4884-4893. Epub 2021 Mar 9.

Department of Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York 14214, United States.

Quantitative proteomics in large cohorts is highly valuable for clinical/pharmaceutical investigations but often suffers from severely compromised reliability, accuracy, and reproducibility. Here, we describe an ultra-high-resolution IonStar method achieving reproducible protein measurement in large cohorts while minimizing the ratio compression problem, by taking advantage of the exceptional selectivity of ultra-high-resolution (UHR)-MS1 detection (240k_FWHM@/ = 200). Using mixed-proteome benchmark sets reflecting large-cohort analysis with technical or biological replicates ( = 56), we comprehensively compared the quantitative performances of UHR-IonStar vs a state-of-the-art SWATH-MS method, each with their own optimal analytical platforms. We confirmed a cutting-edge micro-liquid chromatography (LC)/Triple-TOF with Spectronaut outperforms nano-LC/Orbitrap for SWATH-MS, which was then meticulously developed/optimized to maximize sensitivity, reproducibility, and proteome coverage. While the two methods with distinct principles (i.e., MS1- vs MS2-based) showed similar depth-of-analysis (∼6700-7000 missing-data-free proteins quantified, 1% protein-false discovery rate (FDR) for entire set, 2 unique peptides/protein) and good accuracy/precision in quantifying high-abundance proteins, UHR-IonStar achieved substantially superior quantitative accuracy, precision, and reproducibility for lower-abundance proteins (a category that includes most regulatory proteins), as well as much-improved sensitivity/selectivity for discovering significantly altered proteins. Furthermore, compared to SWATH-MS, UHR-IonStar showed markedly higher accuracy for a single analysis of each sample across a large set, which is an inadequately investigated albeit critical parameter for large-cohort analysis. Finally, we compared UHR-IonStar vs SWATH-MS in measuring the time courses of altered proteins in paclitaxel-treated cells ( = 36), where dysregulated biological pathways have been very well established. UHR-IonStar discovered substantially more well-recognized biological processes/pathways induced by paclitaxel. Additionally, UHR-IonStar showed markedly superior ability than SWATH-MS in accurately depicting the time courses of well known to be paclitaxel-induced biomarkers. In summary, UHR-IonStar represents a reliable, robust, and cost-effective solution for large-cohort proteomic quantification with excellent accuracy and precision.
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http://dx.doi.org/10.1021/acs.analchem.0c05002DOI Listing
March 2021

Improving prediction for medical institution with limited patient data: Leveraging hospital-specific data based on multicenter collaborative research network.

Artif Intell Med 2021 03 23;113:102024. Epub 2021 Jan 23.

Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China; Research center for healthcare data science, Zhejiang Lab, Hangzhou, China. Electronic address:

Background And Objective: Clinical decision support assisted by prediction models usually faces the challenges of limited clinical data and a lack of labels when the model is developed with data from a single medical institution. Accordingly, research on multicenter clinical collaborative networks, which can provide external medical data, has received increasing attention. With the increasing availability of machine learning techniques such as transfer learning, leveraging large-scale patient data from multiple hospitals to build data-driven predictive models with clinical application potential provides an alternative solution to address the problem of limited patient data.

Methods: A multicenter hybrid semi-supervised transfer learning model (MHSTL) is proposed in this study on the basis of unified common data model to ensure multicenter data standardized representation. Then the hospital-specific features, along with the co-occurrence features across domains, are aligned through a representation learning architecture that is built based on deep neural networks and the newly proposed neural decision forest model. In this process, limited patient data from the target hospital, both labeled and unlabeled, are incorporated during the feature adaptation process, thereby contributing to better model performance. Without patient-level data sharing, the proposed model learning strategy which overcomes feature misalignment and distribution divergence, enables the multi-source transfer learning process in the case of insufficient and unlabeled patient data at target hospital.

Results: The effectiveness of the proposed transfer learning model was evaluated on a collaborative research network of colorectal cancer patients in the US and China. The results demonstrate that the proposed model can achieve much better performance for predicting target risk with limited resources on patient data than baseline models      . Better discrimination and calibration ability are also observed when sufficient labeled data are not available in the target hospital for prognosis prediction tasks      . Further exploratory experiments show that the proposed approach exhibits good model generalizability regardless of the data heterogeneity. With the help of the SHapley Additive exPlanations for model interpretation, the effectiveness of incorporating hospital-specific features in the transfer learning model is shown.

Conclusions: In this study, the proposed method can develop prediction models from multiple source hospitals and exhibit good performance by leveraging cross-domain hospital-specific feature information, therefore enhancing the model prediction when applied to single medical institution with limited patient data.
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http://dx.doi.org/10.1016/j.artmed.2021.102024DOI Listing
March 2021