Publications by authors named "Qing Xia"

652 Publications

Contrastive and Selective Hidden Embeddings for Medical Image Segmentation.

IEEE Trans Med Imaging 2022 Jun 29;PP. Epub 2022 Jun 29.

Medical image segmentation is fundamental and essential for the analysis of medical images. Although prevalent success has been achieved by convolutional neural networks (CNN), challenges are encountered in the domain of medical image analysis by two aspects: 1) lack of discriminative features to handle similar textures of distinct structures and 2) lack of selective features for potential blurred boundaries in medical images. In this paper, we extend the concept of contrastive learning (CL) to the segmentation task to learn more discriminative representation. Specifically, we propose a novel patch-dragsaw contrastive regularization (PDCR) to perform patch-level tugging and repulsing. In addition, a new structure, namely uncertainty-aware feature re-weighting block (UAFR), is designed to address the potential high uncertainty regions in the feature maps and serves as a better feature re-weighting. Our proposed method achieves state-of-the-art results across 8 public datasets from 6 domains. Besides, the method also demonstrates robustness in the limited-data scenario. The code is publicly available at https://github.com/lzh19961031/PDCR_UAFR-MIS.
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http://dx.doi.org/10.1109/TMI.2022.3186677DOI Listing
June 2022

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis Oxidative Stress and PI3K/Akt Signaling Pathway.

Front Pharmacol 2022 8;13:896523. Epub 2022 Jun 8.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China.

Obesity-related acute pancreatitis (AP) is characterized by increasing prevalence worldwide and worse clinical outcomes compared to AP of other etiologies. Chaiqin chengqi decoction (CQCQD), a Chinese herbal formula, has long been used for the clinical management of AP but its therapeutic actions and the underlying mechanisms have not been fully elucidated. This study has investigated the pharmacological mechanisms of CQCQD in a novel mouse model of obesity-related alcohol-induced AP (OA-AP). The mouse OA-AP model was induced by a high-fat diet for 12 weeks and subsequently two intraperitoneal injections of ethanol, CQCQD was administered 2 h after the first injection of ethanol. The severity of OA-AP was assessed and correlated with changes in transcriptomic profiles and network pharmacology in the pancreatic and adipose tissues, and further docking analysis modeled the interactions between compounds of CQCQD and their key targets. The results showed that CQCQD significantly reduced pancreatic necrosis, alleviated systemic inflammation, and decreased the parameters associated with multi-organ dysfunction. Transcriptomics and network pharmacology analysis, as well as further experimental validation, have shown that CQCQD induced Nrf2/HO-1 antioxidant protein response and decreased Akt phosphorylation in the pancreatic and adipose tissues. , CQCQD protected freshly isolated pancreatic acinar cells from HO-elicited oxidative stress and necrotic cell death. The docking results of AKT1 and the active compounds related to AKT1 in CQCQD showed high binding affinity. In conclusion, CQCQD ameliorates the severity of OA-AP by activating of the antioxidant protein response and down-regulating of the PI3K/Akt signaling pathway in the pancreas and visceral adipose tissue.
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http://dx.doi.org/10.3389/fphar.2022.896523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213732PMC
June 2022

Predicting persistent organ failure on admission in patients with acute pancreatitis: development and validation of a mobile nomogram.

HPB (Oxford) 2022 Jun 6. Epub 2022 Jun 6.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Early prediction of persistent organ failure (POF) is important for triage and timely treatment of patients with acute pancreatitis (AP).

Methods: All AP patients were consecutively admitted within 48 h of symptom onset. A nomogram was developed to predict POF on admission using data from a retrospective training cohort, validated by two prospective cohorts. The clinical utility of the nomogram was defined by concordance index (C-index), decision curve analysis (DCA), and clinical impact curve (CIC), while the performance by post-test probability.

Results: There were 816, 398, and 880 patients in the training, internal and external validation cohorts, respectively. Six independent predictors determined by logistic regression analysis were age, respiratory rate, albumin, lactate dehydrogenase, oxygen support, and pleural effusion and were included in the nomogram (web-based calculator: https://shina.shinyapps.io/DynNomapp/). This nomogram had reasonable predictive ability (C-indexes 0.88/0.91/0.81 for each cohort) and promising clinical utility (DCA and CIC). The nomogram had a positive likelihood ratio and post-test probability of developing POF in the training, internal and external validation cohorts of 4.26/31.7%, 7.89/39.1%, and 2.75/41%, respectively, superior or equal to other prognostic scores.

Conclusions: This nomogram can predict POF of AP patients and should be considered for clinical practice and trial allocation.
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http://dx.doi.org/10.1016/j.hpb.2022.05.1347DOI Listing
June 2022

An Integrative Analysis of the Immune Features of Inactivated SARS-CoV-2 Vaccine (CoronaVac).

Vaccines (Basel) 2022 May 30;10(6). Epub 2022 May 30.

Department of Chemical Biology, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Currently, an inactivated vaccine has been widely used with encouraging results as a prophylactic agent against COVID-19 infection, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. However, in vitro SARS-CoV-2 vaccine-specific immune features remain elusive, hindering the promotion of a third dose of the vaccine. Here, we present a detailed in vitro immune cellular response and large-scale multi-omics analysis for peripheral blood mononuclear cells (PBMCs) from participants vaccinated with CoronaVac (Sinovac Life Sciences, Beijing, China) and recovered participants from COVID-19. The mean titers of SARS-CoV-2 serum-neutralizing antibodies were significantly increased after the boosting immunization (Day 45) compared to the unimmunized state. We observed that type-1 helper T cells (Th1) tended to dominate after the first dose of vaccine, while humoral immune responses became dominant after the second dose due to the activation of type-2 helper T cell (Th2), memory B cells, and plasmablasts. T follicular helper cells (Tfh) involved in antibody production were activated after the first dose and were maintained for the observed time points. Single-cell RNA sequencing of PBMCs revealed specific changes in cell compositions and gene expression in immunized participants. Multi-omics analysis also demonstrated that CoronaVac-specific serum proteins, plasma metabolites, and plasma lipid changes were skewed to those changes in convalescent patients. Collectively, we provide a comprehensive understanding of CoronaVac-specific in vitro immune features.
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http://dx.doi.org/10.3390/vaccines10060878DOI Listing
May 2022

Screening of Differentially Expressed Genes and miRNAs in Hypothalamus and Pituitary Gland of Sheep under Different Photoperiods.

Genes (Basel) 2022 Jun 19;13(6). Epub 2022 Jun 19.

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.

The reproduction of sheep is affected by many factors such as light, nutrition and genetics. The Hypothalamic-pituitary-gonadal (HPG) axis is an important pathway for sheep reproduction, and changes in HPG axis-related gene expression can affect sheep reproduction. In this study, a model of bilateral ovarian removal and estrogen supplementation (OVX + E) was applied to screen differentially expressed genes and miRNAs under different photoperiods using whole transcriptome sequencing and reveal the regulatory effects of the photoperiod on the upstream tissues of the HPG axis in sheep. Whole transcriptome sequencing was performed in ewe hypothalamus (HYP) and distal pituitary (PD) tissues under short photoperiod 21st day (SP21) and long photoperiod 21st day (LP21). Compared to the short photoperiod, a total of 1813 differential genes (up-regulation 966 and down-regulation 847) and 145 differential miRNAs (up-regulation 73 and down-regulation 72) were identified in the hypothalamus of long photoperiod group. Similarly, 2492 differential genes (up-regulation 1829 and down-regulation 663) and 59 differential miRNAs (up-regulation 49 and down-regulation 10) were identified in the pituitary of long photoperiod group. Subsequently, GO and KEGG enrichment analysis revealed that the differential genes and target genes of differential miRNA were enriched in GnRH, Wnt, ErbB and circadian rhythm pathways associated with reproduction. Combined with sequence complementation and gene expression correlation analysis, several miRNA-mRNA target combinations (e.g., LHB regulated by novel-414) were obtained. Taken together, these results will help to understand the regulatory effect of the photoperiod on the upstream tissues of HPG in sheep.
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http://dx.doi.org/10.3390/genes13061091DOI Listing
June 2022

Role of Seipin in Human Diseases and Experimental Animal Models.

Biomolecules 2022 Jun 17;12(6). Epub 2022 Jun 17.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.

Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 () gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and -associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by gene mutations, paralleled by animal studies including systemic or specific gene knockout, or gene overexpression. In various animal models representing diseases that are not related to mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by gene mutations.
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http://dx.doi.org/10.3390/biom12060840DOI Listing
June 2022

Li-Deficient Materials-Decoration Restrains Oxygen Evolution Achieving Excellent Cycling Stability of Li-Rich Mn-Based Cathode.

ACS Appl Mater Interfaces 2022 Jun 23. Epub 2022 Jun 23.

State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

With the increasing demand for high energy density and rapid charging performance, Li-rich materials have been the up and coming cathodes for next-generation lithium-ion batteries. However, because of oxygen evolution and structural instability, the commercialization of Li-rich materials is extremely retarded by their poor electrochemical performances. In this work, Li-deficient materials LiNbO and (NbLi)TiO are applied to functionalize the surface of LiMnNiCoO, aiming to suppress oxygen evolution and increase structural stability in LIBs. In addition, a fast Li-ion transport channel is beneficial to enhance Li diffusion kinetics. The results demonstrate that the electrodes decorated with LiNbO and (NbLi)TiO materials exhibit more stable cycling stability after long-term cycling and outstanding rate capability.
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http://dx.doi.org/10.1021/acsami.2c03073DOI Listing
June 2022

Spatiotemporal-Resolved Hyperspectral Raman Imaging of Plasmon-Assisted Reactions at Single Hotspots.

Anal Chem 2022 Jun 1;94(23):8174-8180. Epub 2022 Jun 1.

School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, PR China.

Raman spectroscopy facilitates the study of reacting molecules on single nanomaterials. In recent years, the temporal resolution of Raman spectral measurement has been remarkably reduced to the millisecond level. However, the classic scan-based imaging mode limits the application in the dynamical study of reactions at multiple nanostructures. In this paper, we propose a spatiotemporal-resolved Raman spectroscopy (STRS) technology to achieve fast (∼40 ms) and high spatial resolution (∼300 nm) hyperspectral Raman imaging of single nanostructures. With benefits of the outstanding electromagnetic field enhancement factor by surface plasmon resonance (∼10) and the snapshot hyperspectral imaging strategy, we demonstrate the observation of stepwise Raman signals from single-particle plasmon-assisted reactions. Results reveal that the reaction kinetics is strongly affected by not only the surface plasmon-polariton generation but also the density of Raman molecules. In consideration of the spatiotemporal resolving capability of STRS, we anticipate that it provides a potential platform for further extending the application of Raman spectroscopy methods in the dynamic study of 1D or 2D nanostructures.
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http://dx.doi.org/10.1021/acs.analchem.1c05545DOI Listing
June 2022

Synergistic activation of peroxymonosulfate between Co and MnO for bisphenol A degradation with enhanced activity and stability.

J Colloid Interface Sci 2022 Oct 21;623:775-786. Epub 2022 May 21.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P.R. China; Institute of Shaoxing, Tianjin University, Zhejiang, 312099, P.R. China; Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, 300192, P.R. China. Electronic address:

In this work, a novel material of Co Nanoparticles anchored on MnO nanorods wrapped in carbon layers (Co/[email protected]) is successfully synthesized and applied to activate peroxymonosulfate (PMS) for Bisphenol A (BPA) degradation. More than 98% of BPA is removed by Co/[email protected] within 1 min. The reaction rate constant of Co/[email protected] (3.516 min) is much larger than [email protected] (1.076 min) and [email protected] (0.006 min). The leached Co ions from Co/[email protected] (0.97 mg/L) is only 1/5 of [email protected] (4.96 mg/L) after the catalytic reaction. The high activity and low leaching rate of Co indicate the synergistic effect between Co and MnO during PMS activation. Density functional theory (DFT) calculations reveal MnO modified with Co is favorable for the adsorption and activation of PMS and the release of reactive oxidation species (ROSs). The XPS results indicate the presence of Co(III)/Mn(II) redox cycle, while the generated Co(II) and Mn(III) is used for PMS activation, thus proving the synergistic effect further. The open circuit potential (OCP) test proves the direct electron-transfer (DET) exists on the surface of Co/[email protected] Therefore, both radical and nonradical processes are present in the (Co/[email protected])/PMS system. This work provides effective materials and synergistic theory between Co and MnO for environmental remediation.
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http://dx.doi.org/10.1016/j.jcis.2022.05.105DOI Listing
October 2022

Vitamin D and Pancreatitis: A Narrative Review of Current Evidence.

Nutrients 2022 May 18;14(10). Epub 2022 May 18.

Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China.

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.
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http://dx.doi.org/10.3390/nu14102113DOI Listing
May 2022

A Bibliometric Analysis of Knowledge-Hiding Research.

Behav Sci (Basel) 2022 Apr 21;12(5). Epub 2022 Apr 21.

School of Economics and Management, Tongji University, Shanghai 200092, China.

Knowledge hiding, defined as an intentional attempt to conceal requested knowledge, has become a hot topic in management and psychology in the last decade. Emerging research has suggested that knowledge hiding is not simply the opposite of knowledge sharing, such that it is crucial to clarify the concept, explore the research progress and development trend of knowledge hiding. Based on 243 relevant articles, a bibliometric analysis of knowledge-hiding research is presented via descriptive, keyword and citation analysis. Results reveal that knowledge-hiding research, mainly focusing on the disciplines of management, business and psychology, is currently in a period of rapid growth, especially in the past two or three years. The systematic review of knowledge-hiding research enables us intuitively to obtain a panoramic view, including publication performance, thematic evolution and most influential topics of the field via a set of science maps, enabling future authors to investigate knowledge hiding and focus their research more effectively.
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http://dx.doi.org/10.3390/bs12050122DOI Listing
April 2022

L-Borneol 7-O-[-D-Apiofuranosyl-(1→6)]--D-Glucopyranoside Alleviates Myocardial Ischemia-Reperfusion Injury in Rats and Hypoxic/Reoxygenated Injured Myocardial Cells via Regulating the PI3K/AKT/mTOR Signaling Pathway.

J Immunol Res 2022 12;2022:5758303. Epub 2022 May 12.

Department of Pharmacology, Ningbo College of Health Sciences, Ningbo, Zhejiang, China.

Ischemia/reperfusion (I/R) is a primary cause of morbidity and mortality in acute myocardial infarction (AMI). L-Borneol 7-O-[-D-apiofuranosyl-(1→6)]--D-glucopyranoside (LBAG), extracted from the Radix Ophiopogonis, is the main bioactive component that may be exerting cardiovascular protection in AMI. The purpose was to examine the effects of LBAG on myocardial I/R injury (MIRI) in rats and H9c2 cells treated with hypoxia/reoxygenation (H/R). MIRI was induced through the combination of ischemia with reperfusion for 30 min and 24 h, respectively. LBAG was administered 7 days before vascular ligation. Myocardial function was detected by an electrocardiograph, histological, TTC, and TUNEL staining analyses. The influences of LBAG on the content concentration of cardiac enzymes in the serum were measured by ELISA. Moreover, H9c2 cells were exposed to LBAG or combined with AKT inhibitor (perifosine) and then exposed to H/R for simulating the cardiac injury process. Afterward, cell viability, LDH, CD-KM release, apoptosis, and autophagy were evaluated by CCK-8 and ELISA assays, flow cytometry, TUNEL, and immunofluorescence staining, respectively. Additionally, the proteins of apoptosis, autophagy, and PI3K/mTOR pathway were determined by western blotting. In I/R rats, LBAG pretreatment significantly ameliorated cardiac function, as illustrated by reducing the infarct size, myocardial autophagy, and apoptosis levels. In H/R-induced H9c2 cells, LBAG pretreatment significantly decreased cell apoptosis, LC3 II/I, and Beclin 1 levels, elevated the Bcl-2 levels, attenuated LDH, and CD-KM production. Moreover, LBAG pretreatment markedly increased the PI3K/mTOR pathway activation, and the protective influences of LBAG were partly abolished with the AKT inhibitor perifosine treatment. These findings demonstrated the protective functions of LBAG on I/R by regulating apoptosis and autophagy in vitro and in vivo by activating the PI3K/mTOR pathway.
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http://dx.doi.org/10.1155/2022/5758303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119761PMC
May 2022

Berberine induces non-small cell lung cancer apoptosis via the activation of the ROS/ASK1/JNK pathway.

Ann Transl Med 2022 Apr;10(8):485

Department of Respiratory and Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Berberine (BBR), an isoquinoline alkaloid, is commonly used in traditional Chinese medicine. Previous studies have shown that BBR has a potential anti-tumor effect. However, the mechanisms of BBR on mitochondrial function in anti-lung cancer remain unknown. The aim of this study was to explore mitochondrial function in anti-tumor mechanisms of BBR in NSCLC.

Methods: The NSCLCs were cultured and treated with various doses (40, 80, 120 µg/mL) of BBR for 24 and 48 h. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8). Cell apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. Relative protein expression was examined by western blot and immunohistochemical (IHC) analysis.

Results: BBR potently suppressed NSCLC cells growth by inducing apoptosis in a dose-and time-dependent manner. BBR induced apoptosis in NSCLC cells as evidenced by caspase-3 cleavage, cytochrome c release, and mitochondrial membrane depolarization. BBR-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of c-jun-NH2-kinase (JNK) and the JNK inhibitor (SP600125) significantly suppressed BBR-induced apoptosis, N-acetyl cysteine (NAC), a ROS scavenger, was sufficient to both suppress apoptosis signal-regulating kinase 1 (ASK1) and JNK activation and disrupt apoptotic induction.

Conclusions: The results suggest that BBR induces apoptosis of NSCLC cells via ROS-mediated ASK1/JNK activation and the mitochondrial pathway.
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http://dx.doi.org/10.21037/atm-22-1298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096398PMC
April 2022

MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2.

Br J Cancer 2022 Apr 30. Epub 2022 Apr 30.

State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China.

Background: The mechanism of recurrence and metastasis of hepatocellular carcinoma (HCC) is complex and challenging. Methyl-CpG binding domain protein 3 (MBD3) is a key epigenetic regulator involved in the progression and metastasis of several cancers, but its role in HCC remains unknown.

Methods: MBD3 expression in HCC was detected by immunohistochemistry and its association with clinicopathological features and patient's survival was analysed. The effects of MBD3 on hepatoma cells growth and metastasis were investigated, and the mechanism was explored.

Results: MBD3 is significantly highly expressed in HCC, associated with the advanced tumour stage and poor prognosis in HCC patients. MBD3 promotes the growth, angiogenesis and metastasis of HCC cells by inhibiting the tumour suppressor tissue factor pathway inhibitor 2 (TFPI2). Mechanistically, MBD3 can inhibit the TFPI2 transcription via the Nucleosome Remodeling and Deacetylase (NuRD) complex-mediated deacetylation, thus reactivating the activity of matrix metalloproteinases (MMPs) and PI3K/AKT signaling pathway, leading to the progression and metastasis of HCC CONCLUSIONS: Our results unravel the novel regulatory function of MBD3 in the progression and metastasis of HCC and identify MBD3 as an independent unfavourable prognostic factor for HCC patients, suggesting its potential as a promising therapeutic target as well.
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http://dx.doi.org/10.1038/s41416-022-01831-5DOI Listing
April 2022

Realizing high performance flexible supercapacitors by electrode modification.

RSC Adv 2021 Dec 7;11(62):39045-39050. Epub 2021 Dec 7.

School of Materials Science and Engineering, Shenyang University of Technology Shenyang 110870 P. R. China

It is well known that the structure of an electrode material seriously affects its electrochemical performance. In this study, we prepare hybrid structured [email protected] nanoarchitectures by a hydrothermal method and subsequent electrodeposition process. The specific capacitance of the obtained sample is 1733.23 C g at 1 A g. The assembled asymmetric device presents an energy density of 59.59 W h kg at 1404.04 W kg. The excellent electrochemical performance can be attributed to the synergistic effect between the high theoretical specific capacitance of the NiCoS sheets and the superior cycling stability of the PPy film. The device also shows an outstanding mechanical flexibility at different bending angles.
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http://dx.doi.org/10.1039/d1ra07880aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044427PMC
December 2021

Transcriptomic Changes of Photoperiodic Response in the Hypothalamus Were Identified in Ovariectomized and Estradiol-Treated Sheep.

Front Mol Biosci 2022 11;9:848144. Epub 2022 Apr 11.

Key Laboratory of Animal Genetics and Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

Accurate timing of seasonal changes is an essential ability for an animal's survival, and the change in the photoperiod is the key factor affecting reproductive seasonality in mammals. Emerging evidence has suggested that multiple hypothalamic genes participate in the photoperiod-induced regulation of reproductive activities in sheep, but the mechanism is still unclear. In this study, we initially examined the plasma level of two major reproductive hormones, namely, follicle-stimulating hormone (FSH) and prolactin (PRL), under different photoperiods in ovariectomized and estradiol-treated (OVX + E) sheep using radioimmunoassay (RIA). Of the two hormones, the concentration of PRL significantly increased with the extension of the photoperiod, while FSH showed the opposite trend. Subsequently, an examination of the transcriptomic variation between the short photoperiod (SP) and long photoperiod (LP) was conducted. Differential expression analyses and functional annotation showed that several key genes in the insulin secretion (, , , and ), GnRH (, , , , and ) pathways, and circadian entrainment (, , , , and ), as well as numerous lncRNAs, including XR_173257.3, XR_173415.3, XR_001435315.1, XR_001024596.2, and XR_001023464.2, were shown potentially vital for the hypothalamic photoperiodic response. Four of the differentially expressed mRNAs and lncRNAs were validated by qPCR. The constructed mRNA-mRNA interaction networks further revealed that transcripts potentially participated in hypothalamic thyroid hormone synthesis, endocrine resistance, and neuroactive ligand-receptor interactions. The interactome analysis of lncRNAs and their targets implied that XR_173257.3 and its target arylalkylamine N-acetyltransferase () and XR_173415.3 and its target might participate in the regulation of seasonal reproduction. Together, the changes in reproductive hormones and transcriptome will help to determine the important photoperiod-induced lncRNAs and mRNAs and provide a valuable resource for further research on reproductive seasonality in sheep.
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http://dx.doi.org/10.3389/fmolb.2022.848144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036065PMC
April 2022

Design of ferrocenylseleno-dopamine derivatives to optimize the Fenton-like reaction efficiency and antitumor efficacy.

RSC Adv 2021 Jul 22;11(41):25477-25483. Epub 2021 Jul 22.

School of Chemistry and Molecular Engineering, Nanjing Tech University Nanjing 211816 China

In the current study, six ferrocenylseleno-dopamine derivatives with different structural parameters were designed. Among these derivatives, F4b, containing two ferrocene units and a tertiary amine, showed anticancer activity with IC = 2.4 ± 0.4 μM for MGC-803 cells, and its studies suggested effective antitumor activity in mice bearing an MGC-803 tumor xenograft. Mechanistic study revealed that the cytotoxicity of these ferrocenylseleno-dopamine derivatives is mainly related to the Fenton-like reaction under physiological conditions, and the tertiary amine in F4b can facilitate the HO decomposition to generate toxic ˙OH which induces apoptosis through CDK-2 inactivation.
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http://dx.doi.org/10.1039/d1ra03537aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036967PMC
July 2021

Alcohol predisposes obese mice to acute pancreatitis via adipose triglyceride lipase-dependent visceral adipocyte lipolysis.

Gut 2022 Apr 22. Epub 2022 Apr 22.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, People's Republic of China

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http://dx.doi.org/10.1136/gutjnl-2022-326958DOI Listing
April 2022

Predicting the Need for Therapeutic Intervention and Mortality in Acute Pancreatitis: A Two-Center International Study Using Machine Learning.

J Pers Med 2022 Apr 11;12(4). Epub 2022 Apr 11.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610044, China.

Background: Current approaches to predicting intervention needs and mortality have reached 65-85% accuracy, which falls below clinical decision-making requirements in patients with acute pancreatitis (AP). We aimed to accurately predict therapeutic intervention needs and mortality on admission, in AP patients, using machine learning (ML).

Methods: Data were obtained from three databases of patients admitted with AP: one retrospective (Chengdu) and two prospective (Liverpool and Chengdu) databases. Intervention and mortality differences, as well as potential predictors, were investigated. Univariate analysis was conducted, followed by a random forest ML algorithm used in multivariate analysis, to identify predictors. The ML performance matrix was applied to evaluate the model's performance.

Results: Three datasets of 2846 patients included 25 potential clinical predictors in the univariate analysis. The top ten identified predictors were obtained by ML models, for predicting interventions and mortality, from the training dataset. The prediction of interventions includes death in non-intervention patients, validated with high accuracy (96%/98%), the area under the receiver-operating-characteristic curve (0.90/0.98), and positive likelihood ratios (22.3/69.8), respectively. The post-test probabilities in the test set were 55.4% and 71.6%, respectively, which were considerably superior to existing prognostic scores. The ML model, for predicting mortality in intervention patients, performed better or equally with prognostic scores.

Conclusions: ML, using admission clinical predictors, can accurately predict therapeutic interventions and mortality in patients with AP.
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http://dx.doi.org/10.3390/jpm12040616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031087PMC
April 2022

Web Crawling and mRNA Sequencing Analyze Mechanisms of Photobiomodulation.

Photobiomodul Photomed Laser Surg 2022 Apr;40(4):252-260

The Heilongjiang Key Laboratory of Immunity and Infection Harbin Medical University, Department of Microbiology, Wu Lien-Teh Institute, Harbin, P.R. China.

Photobiomodulation (PBM) is praised as a promising physical therapy, which has many advantages, such as being noninvasive and painless. However, the mechanisms are not fully elucidated. Using web crawling, mRNA sequence, and bioinformatics analysis, we selected genes, functional annotation, and mechanisms. The expressions of inflammatory cytokines were measured using quantitative real-time PCR (RT-qPCR). A total of 146 human genes and 57 pathways were identified about PBM. The 630 nm light-emitting diode (LED)-stimulated-MH7A cells were sequenced to further analyze the mechanism of PBM. Two thousand nine hundred fifty differentially expressed genes were identified, and the gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. The 12 pathways were matched with the KEGG results of PBM and MH7A cells. A protein-protein interaction network was performed among genes in 12 pathways, and 10 outstanding proteins were identified. Importantly, the 9 genes were predicted with potential research value. And we also demonstrated that expression of inflammatory factors [interleukin (IL)-6, IL-1β, IL-8, and matrix metalloproteinase-3 (MMP-3)] was reduced; meanwhile, the expression of anti-inflammatory factor IL-10 was promoted after 630 nm LED. Using web crawling, bioinformatics analysis, and mRNA sequence, we obtained 9 key genes and 12 important pathways about PBM. Importantly, we demonstrated the anti-inflammatory effect of 630 nm LED red light by RT-qPCR.
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http://dx.doi.org/10.1089/photob.2021.0142DOI Listing
April 2022

Inverse association between ambient particulate matter and semen quality in Central China: Evidence from a prospective cohort study of 15,112 participants.

Sci Total Environ 2022 Aug 12;833:155252. Epub 2022 Apr 12.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; The Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Anhui Medical University, Hefei, Anhui, China. Electronic address:

Emerging evidence indicates that ambient particulate matter (PM) is harmful to male fertility, but the associations between ambient PM exposure and semen quality were inconsistent. This study aimed to quantitatively evaluate the association between ambient PM exposure and semen quality based on a large prospective cohort. Using data from the prospective assisted reproduction cohort in Anhui province, China, we included 15,112 males with 28,267 semen tests, whose partner has undergone assisted reproductive technology from September 1, 2015 to September, 22 2020. Individual ambient PM, gaseous air pollutants, and temperature exposures of the participants during 0-90, 0-9, 10-14, and 70-90 days before semen quality tests were evaluated using inverse distance weighting interpolation. Linear mixed-effects models were conducted to evaluate the relationship between PM and PM exposures and standardized semen quality parameters. Models were adjusted for age, body mass index, smoking, drinking, education attainment, occupation type, sampling month, temperature and the principal component of gaseous air pollutants. PM and PM were inversely associated with sperm concentration, total sperm count, total motility, progressive motility, total motile sperm count, and progressively motile sperm count during 0-90, 0-9, and 70-90 days period (all p < 0.05), but not 10-14 days period. The regression coefficients of PM exposure on semen quality parameters during 0-90 days period were larger than 0-9 and 70-90 days periods, and the effects of PM on semen quality parameters were stronger than PM. Our results showed that ambient PM and PM exposures were associated with semen quality, during 70-90 days and 0-9 days before sampling, and the entire spermatogenesis process. The effects of PM on semen quality parameters were stronger than PM, and the long-term effects of PM and PM, throughout spermatogenesis, were stronger than the short-term effects.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155252DOI Listing
August 2022

A reduction-responsive drug delivery with improved stability: disulfide crosslinked micelles of small amiphiphilic molecules.

RSC Adv 2021 Mar 1;11(21):12757-12770. Epub 2021 Apr 1.

School of Chemistry and Chemical Engineering, Southeast University Nanjing 214122 China

Micelles self-assembled from small amphiphilic molecules are unstable in biological fluids, and thus are poor drug carriers. In contrast, amphiphilic polymer micelles can encapsulate hydrophobic drugs in their core to greatly enhance their aqueous solubility and extend their retention time in blood circulation owing to their hydrophilic shell. However, the major disadvantages of conventional polymer micelles are the heterogeneity of the amphiphilic polymer structure and premature drug leakage. Thus, herein, to address these shortcomings, disulfide crosslinked micelles composed of a small amphiphilic molecule, di-lipoyl-glycerophosphorylcholine (di-LA-PC), were developed as redox-responsive drug carriers. Specifically, di-LA-PC was synthesized and self-assembled to form crosslinked micelles under catalysis by dithiothreitol. The disulfide crosslinked micelles maintained high stability in a simulated physiological environment, but rapidly disassembled under reductive conditions. Furthermore, paclitaxel (PTX), as a model drug, was encapsulated in the core of the crosslinked micelles with a high loading content of 8.13%. The release studies indicated that over 80% of PTX was released from the micelles in the reductive environment, whereas less than 20% PTX was released without reduction in the 68 h test. Benefiting from their nanoscale characteristics, the PTX-loaded micelles showed efficient cellular internalization and effectively induced the death of cancer cells, as revealed in the MTT, apoptosis and cell cycle tests. Moreover, pharmacokinetic studies demonstrated that the crosslinked micelles prolonged the circulation of the incorporated PTX in the bloodstream and increased its accumulation in the tumor tissue the EPR effect. Finally, the PTX-loaded micelles displayed prominent anti-tumor activity in a 4T1 xenograft tumor model. In summary, the di-LA-PC crosslinked micelle platform possesses excellent stability, high loading capacity and reduction-responsive release profile, which may have applications in the delivery of PTX and other anti-cancer drugs.
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http://dx.doi.org/10.1039/d1ra00079aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697188PMC
March 2021

Decorating Bacteria with Triple Immune Nanoactivators Generates Tumor-Resident Living Immunotherapeutics.

Angew Chem Int Ed Engl 2022 Jul 9;61(27):e202202409. Epub 2022 May 9.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

An approach of decorating bacteria with triple immune nanoactivators is reported to develop tumor-resident living immunotherapeutics. Under cytocompatible conditions, tumor-specific antigens and checkpoint blocking antibodies are simultaneously conjugated onto bacterial surface and then polydopamine nanoparticles are formed via in situ dopamine polymerization. In addition to serving as a linker, polydopamine with its photothermal effect can repolarize tumor-associated macrophages to a pro-inflammatory phenotype. The linked antigens promote the maturation of dendritic cells and generate tumor-specific immune responses, while the anchored antibodies block immune checkpoints and activate cytotoxic T lymphocytes. Decorated bacteria show spatiotemporal tumor retention and proliferation-dependent drug release, achieving potent antitumor effects in two antigen-overexpressing tumor models. This work provides a versatile platform to prepare multimodal and long-acting therapeutics for cancer immunotherapy.
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http://dx.doi.org/10.1002/anie.202202409DOI Listing
July 2022

Recent advances in heterostructured cathodic electrocatalysts for non-aqueous Li-O batteries.

Chem Sci 2022 Mar 22;13(10):2841-2856. Epub 2021 Dec 22.

Institute for Carbon Neutralization, College of Chemistry and Materials Engineering, Wenzhou University Wenzhou 325035 China

Developing efficient energy storage and conversion applications is vital to address fossil energy depletion and global warming. Li-O batteries are one of the most promising devices because of their ultra-high energy density. To overcome their practical difficulties including low specific capacities, high overpotentials, limited rate capability and poor cycle stability, an intensive search for highly efficient electrocatalysts has been performed. Recently, it has been reported that heterostructured catalysts exhibit significantly enhanced activities toward the oxygen reduction reaction and oxygen evolution reaction, and their excellent performance is not only related to the catalyst materials themselves but also the special hetero-interfaces. Herein, an overview focused on the electrocatalytic functions of heterostructured catalysts for non-aqueous Li-O batteries is presented by summarizing recent research progress. Reduction mechanisms of Li-O batteries are first introduced, followed by a detailed discussion on the typical performance enhancement mechanisms of the heterostructured catalysts with different phases and heterointerfaces, and the various heterostructured catalysts applied in Li-O batteries are also intensively discussed. Finally, the existing problems and development perspectives on the heterostructure applications are presented.
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http://dx.doi.org/10.1039/d1sc05781bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905958PMC
March 2022

Ketogenesis acts as an endogenous protective programme to restrain inflammatory macrophage activation during acute pancreatitis.

EBioMedicine 2022 Apr 25;78:103959. Epub 2022 Mar 25.

State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Centre, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Rd, Shanghai 200127 China. Electronic address:

Background: Innate immunity and metabolites link to the pathogenesis and severity of acute pancreatitis (AP). However, liver metabolism and its role in immune response and AP progression remain elusive. We investigated the function of liver metabolism in the pathogenesis of AP.

Methods: Circulating ketone body β-hydroxybutyrate (βOHB) levels were determined in AP clinical cohorts and caerulein-induced AP (CER-AP) mouse models receiving seven (Cer*7) or twelve (Cer*12) injection regimens at hourly intervals. Liver transcriptomics and metabolomics were compared between CER-AP (Cer*7) and CER-AP (Cer*12). Inhibition of fatty acid β-oxidation (FAO)-ketogenesis, or supplementation of βOHB was performed in mouse models of AP. The effect and mechanism of βOHB were examined in vitro.

Findings: Elevated circulating βOHB was observed in patients with non-severe AP (SAP) but not SAP. These findings were replicated in CER-AP (Cer*7) and CER-AP (Cer*12), which manifested as limited and hyperactive immune responses, respectively. FAO-ketogenesis was activated in CER-AP (Cer*7), while impaired long-chain FAO and mitochondrial function were observed in the liver of CER-AP (Cer*12). Blockage of FAO-ketogenesis (Cpt1a antagonism or Hmgcs2 knockdown) worsened, while supplementation of βOHB or its precursor 1,3-butanediol alleviated the severity of CER-AP. Mechanistically, βOHB had a discernible effect on pancreatic acinar cell damage, instead, it greatly attenuated the activation of pancreatic and systemic proinflammatory macrophages via class I histone deacetylases.

Interpretation: Our findings reveal that hepatic ketogenesis is activated as an endogenous protective programme to restrain AP progression, indicating its potential therapeutic value.

Funding: This work was supported by the National Natural Science Foundation of China, Shanghai Youth Talent Support Programme, and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant.
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http://dx.doi.org/10.1016/j.ebiom.2022.103959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960978PMC
April 2022

Impact of airborne total suspended particles (TSP) and fine particulate matter (PM )-induced developmental toxicity in zebrafish (Danio rerio) embryos.

J Appl Toxicol 2022 Mar 21. Epub 2022 Mar 21.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, China.

Airborne total suspended particles (TSP) and particulate matter (PM ) threaten global health and their potential impact on cardiovascular and respiratory diseases are extensively studied. Recent studies attest premature deaths, low birth weight, and congenital anomalies in the fetus of pregnant women exposed to air pollution. In this regard, only few studies have explored the effects of TSP and PM on cardiovascular and cerebrovascular development. As both TSP and PM differ in size and composition, this study is attempted to assess the variability in toxicity effects between TSP and PM on the development of cardiovascular and cerebrovascular systems and the underlying mechanisms in a zebrafish model. To explore the potential toxic effects of TSP and PM , zebrafish embryos/larvae were exposed to 25, 50, 100, 200, and 400 μg/ml of TSP and PM from 24 to 120 hpf (hours post-fertilization). Both TSP and PM exposure increased the rate of mortality, malformations, and oxidative stress, whereas locomotor behavior, heart rate, blood flow velocity, development of cardiovasculature and neurovasculature, and dopaminergic neurons were reduced. The expression of genes involved in endoplasmic reticulum stress (ERS), Wnt signaling, and central nervous system (CNS) development were altered in a dose- and time-dependent manner. This study provides evidence for acute exposure to TSP and PM -induced cardiovascular and neurodevelopmental toxicity, attributed to enhanced oxidative stress and aberrant gene expression. Comparatively, the effects of PM were more pronounced than TSP.
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http://dx.doi.org/10.1002/jat.4325DOI Listing
March 2022

Diversity investigation by application of DNA barcoding: A case study of lepidopteran insects in Xinjiang wild fruit forests, China.

Ecol Evol 2022 Feb 7;12(3):e8678. Epub 2022 Mar 7.

Key Laboratory of Plant Protection Resources and Pest Management Ministry of Education Northwest A&F University Yangling China.

To investigate the species diversity of lepidopteran insects in Xinjiang wild fruit forests, establish insect community monitoring systems, and determine the local species pool, we test the applicability of DNA barcoding based on cytochrome oxidase subunit I () gene for accurate and rapid identification of insect species. From 2017 to 2019, a total of 212 samples with ambiguous morphological identification were selected for DNA barcoding analysis. Five sequence-based methods for species delimitation (ABGD, BINs, GMYC, jMOTU, and bPTP) were conducted for comparison to traditional morphology-based identification. In total, 2,422 samples were recorded, representing 143 species of 110 genera in 17 families in Lepidoptera. The diversity analysis showed that the richness indices for Noctuidae was the highest (54 species), and for Pterophoridae, Cossidae, Limacodidae, Lasiocampidae, Pieridae, and Lycaenidae were the lowest (all with 1 species). The Shannon-Wiener species diversity index (H') and Pielou's evenness (J') of lepidopteran insects first increased and then decreased across these 3 years, while the Simpson diversity index showed a trend of subtracted then added. For molecular-based identification, 67 lepidopteran species within 61 genera in 14 families were identified through DNA barcoding. Neighbor-joining (NJ) analysis showed that conspecific individuals were clustered together and formed monophyletic groups with a high support value, except for (Denis & Schiffermüller, 1775) (Noctuidae: Hadeninae). Sixty-seven morphospecies were classified into various numbers of MOTUs based on ABGD, BINs, GMYC, jMOTU, and bPTP (70, 96, 2, 71, and 71, respectively). In Xinjiang wild fruit forests, the family with the largest number of species is Noctuidae, followed by Geometridae, Crambidae, and the remaining families. The highest Shannon diversity index is observed for the family Noctuidae. Our results indicate that the distance-based methods (ABGD and jMOTU) and character-based method (bPTP) outperform GMYC. BINs is inclined to overestimate species diversity compared to other methods.
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http://dx.doi.org/10.1002/ece3.8678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901863PMC
February 2022

Carnosine Improves Cognitive Impairment Through Promoting SIRT6 Expression and Inhibiting Endoplasmic Reticulum Stress in a Diabetic Encephalopathy Model.

Rejuvenation Res 2022 Apr;25(2):79-88

Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Diabetic encephalopathy (DE) is one of complications of diabetes mellitus. Carnosine is a dipeptide composed of β-alanine and l-histidine. Study has shown that carnosine could ameliorate cognitive impairment in animal model with diabetes mellitus. However, the mechanism remains unclear. An animal model of type 2 diabetes (db/db mice) was used in this study. The animals were treated with 0.9% saline or carnosine (100 mg/kg) for 8 weeks. Morris water maze was tested after drug administration. Oxidative stress-related factors malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and pro-inflammatory factors inducible nitric oxide synthase (iNOS) were measured. Synapse-related protein postsynaptic density 95 (PSD95) and brain-derived neurotrophic factor (BDNF) were detected by western blot. Besides, the expressions of sirtuin 6 (SIRT6), binding immunoglobulin protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phospho-protein kinase R-like endoplasmic reticulum kinase (P-PERK), inositol-requiring enzyme-1α (IRE1α), phospho-inositol-requiring enzyme-1α (P-IRE1α), activating transcription factor 6 (ATF6), and C/EBP-homologous protein (CHOP) in the hippocampus of the brain were detected. The results showed that treatment with carnosine ameliorated cognitive impairment in db/db mice. Carnosine reduced neuronal oxidative stress damage and iNOS expression in db/db mice. Meanwhile, carnosine relieved neurodegeneration in the hippocampus of db/db mice. Furthermore, carnosine promoted the expression of SIRT6 and reduced the expressions of endoplasmic reticulum (ER)-related factors (BIP, P-PERK, P-IRE1α, ATF6, and CHOP). In conclusion, these data suggested that the protective effect of carnosine against DE might be related to SIRT6/ER stress pathway.
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http://dx.doi.org/10.1089/rej.2022.0002DOI Listing
April 2022

Mortality and survival in idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

ERJ Open Res 2022 Jan 14;8(1). Epub 2022 Mar 14.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Background: There are substantial advances in diagnosis and treatment for idiopathic pulmonary fibrosis (IPF), but without much evidence available on recent mortality and survival trends.

Methods: A narrative synthesis approach was used to investigate the mortality trends, then meta-analyses for survival trends were carried out based on various time periods.

Results: Six studies reported the mortality data for IPF in 22 countries, and 62 studies (covering 63 307 patients from 20 countries) reported survival data for IPF. Age-standardised mortality for IPF varied from ∼0.5 to ∼12 per 100 000 population per year after year 2000. There were increased mortality trends for IPF in Australia, Brazil, Belgium, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Lithuania, the Netherlands, Poland, Portugal, Spain, Sweden and UK, while Austria, Croatia, Denmark, Romania and the USA showed decreased mortality trends. The overall 3-year and 5-year cumulative survival rates (CSRs) were 61.8% (95% CI 58.7-64.9; I=97.1%) and 45.6% (95% CI 41.5-49.7; I=97.7%), respectively. Prior to 2010, the pooled 3-year CSR was 59.9% (95% CI 55.8-64.1; I=95.8%), then not significantly (p=0.067) increased to 66.2% (95% CI 62.9-69.5; I=92.6%) in the 2010s decade. After excluding three studies in which no patients received antifibrotics after year 2010, the pooled 3-year CSRs significantly (p=0.039) increased to 67.4% (95% CI 63.9-70.9; I=93.1%) in the 2010s decade.

Discussion: IPF is a diagnosis associated with high mortality. There was no observed increasing survival trend for patients with IPF before year 2010, with then a switch to an improvement, which is probably multifactorial.
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http://dx.doi.org/10.1183/23120541.00591-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918939PMC
January 2022
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