Publications by authors named "Long Chen"

1,406 Publications

  • Page 1 of 1

Slowdown of Water Dynamics from the Top to the Bottom of the GroEL Cavity.

J Phys Chem Lett 2021 Jun 15:5723-5730. Epub 2021 Jun 15.

Department of Physics, The Ohio State University, Columbus, Ohio 43210, United States.

The GroE molecular chaperone system is a critical protein machine that assists the folding of substrate proteins in its cavity. Water in the cavity is suspected to play a role in substrate protein folding, but the mechanism is currently unknown. Herein, we report measurements of water dynamics in the equatorial and apical domains of the GroEL cavity in the apo and football states, using site-specific tryptophanyl mutagenesis as an intrinsic optical probe with femtosecond resolution combined with molecular dynamics simulations. We observed clearly different water dynamics in the two domains with a slowdown of the cavity water from the apical to equatorial region in the football state. The results suggest that the GroEL cavity provides a unique water environment that may facilitate substrate protein folding.
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http://dx.doi.org/10.1021/acs.jpclett.1c01216DOI Listing
June 2021

An Escherichia coli isolate from hospital sewage carries bla and bla.

Arch Microbiol 2021 Jun 15. Epub 2021 Jun 15.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.

Carbapenems, as the "last line of defense" against Gram-negative bacteria, are increasingly being challenged by drug-resistant bacteria, especially Enterobacteriaceae. In this study, a carbapenem-resistant Gram-negative bacterium, named AH001, was isolated from hospital sewage, and a modified Hodge test confirmed that this bacterium can produce carbapenemase. Further analysis revealed that this bacterium exhibits multidrug resistance against an additional seven antibiotics. Whole-genome sequencing and analysis showed that AH001 could not be classified by existing MLST, and its serotype could not be distinguished among O9, O89 or O168 according to O antigen prediction. More attention should be given to the role of environmental sources of Escherichia coli in the development and transfer of drug resistance in the hospital environment.
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http://dx.doi.org/10.1007/s00203-021-02431-2DOI Listing
June 2021

FGF21 promotes wound healing of rat brain microvascular endothelial cells through facilitating TNF-α-mediated VEGFA and ERK1/2 signaling pathway.

Adv Clin Exp Med 2021 Jun 11. Epub 2021 Jun 11.

No. 1 Department of Orthopedics, The Third People's Hospital, Cixi, China.

Background: Wound healing is an essential physiological process in recovery after microsurgery.

Objectives: To further understand the functions of fibroblast growth factor 21 (FGF21), the roles of this factor were examined and its correlations with inflammation, vascular endothelial growth factor A (VEGFA) and ERK1/2 signaling pathway activation were analyzed.

Material And Methods: Rat brain microvascular endothelial cells (RBMECs) were treated with interleukin (IL)-1β and used for the experiments. Cell Counting Kit-8 (CCK-8) was used to detect the cell viability of RBMECs after treatment with IL-1β (1 ng/mL) and FGF21 or VEGFA overexpression, while changes in apoptosis were measured through flow cytometry. Migration was checked through the scratch test. FGF21 and VEGFA RNA expression was assessed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), which was also used to examine RNA expression of Bcl-2, Bax and caspase-3. After IL-1β treatment and FGF21 overexpression, tumor necrosis factor alpha (TNF-α) and tumor growth factor β1 (TGF-β1) proteins level were observed with enzyme-linked immunosorbent assay (ELISA), which was also applied to check the expression of ERK1/2 after overexpression of FGF21 and VEGFA. PD98059 (50 μM), an ERK1/2 inhibitor, was used to examine the roles of ERK1/2 in regulating cell viability and apoptosis.

Results: The IL-1β treatment significantly decreased the viability of RBMECs and TGF-β1, but promoted cell apoptosis and TNF-α expression. FGF21 was downregulated by IL-1β treatment but its overexpression enhanced the viability of RBMECs and TGF-β1 and ERK1/2 protein levels, and attenuated cell apoptosis and TNF-α. Upregulated TNF-α restrained cell viability and apoptosis of RBMECs after FGF21 overexpression, and its upregulation not only suppressed FGF21, but also VEGFA. Moreover, VEGFA suppression by TNF-α increased cell viability and ERK1/2 protein levels, and suppressed the apoptosis of RBMECs through its upregulation. However, PD98059 obstructed the functions of FGF21 and VEGFA.

Conclusions: FGF21 promoted the cell viability of RBMECs through upregulating TNF-α-mediated VEGFA and ERK1/2 signaling.
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http://dx.doi.org/10.17219/acem/133494DOI Listing
June 2021

Complete genome analysis of the newly isolated Shigella sonnei phage vB_SsoM_Z31.

Arch Virol 2021 Jun 11. Epub 2021 Jun 11.

Dalian SEM Bio-Engineering Technology Co. Ltd, Dalian, 116620, China.

This work describes the characterization and genome annotation of the newly isolated lytic phage vB_SsoM_Z31 (referred to as Z31), isolated from wastewater samples collected in Dalian, China. Transmission electron microscopy revealed that phage Z31 belongs to the family Myoviridae, order Caudovirales. This phage specifically infects Shigella sonnei, Shigella dysenteriae, and Escherichia coli. The genome of the phage Z31 is an 89,355-bp-long dsDNA molecule with a G+C content of 38.87%. It was predicted to contain 133 ORFs and encode 24 tRNAs. No homologs of virulence factor genes or antimicrobial resistance genes were found in this phage. Based on the results of nucleotide sequence alignment and phylogenetic analysis, phage Z31 was assigned to the genus Felixounavirus, subfamily Ounavirinae.
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http://dx.doi.org/10.1007/s00705-021-05121-yDOI Listing
June 2021

Gut Microbiota in Psychiatric Disorders: A Systematic Review.

Psychosom Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet Stockholm Health Care Services, Stockholm County Council, Karolinska University Hospital, Huddinge, Sweden Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Public Health, Section for Health Services Research, University of Copenhagen, Denmark Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, USA.

Objective: This systematic review sought to comprehensively summarize gut microbiota research in psychiatric disorders following PRISMA guidelines.

Methods: Literature searches were performed on databases using keywords involving gut microbiota and psychiatric disorders. Articles in English with human participants up until 13th of February 2020 were reviewed. Risk of bias was assessed using a modified Newcastle-Ottawa scale for microbiota studies.

Results: Sixty-nine of 4231 identified studies met inclusion criteria for extraction. In most studies, gut microbiota composition differed between individuals with psychiatric disorders and healthy controls; however, limited consistency was observed in the taxonomic profiles. At the genus level, the most replicated findings were higher abundance of Bifidobacterium, and lower abundance of Roseburia and Faecalibacterium among patients with psychiatric disorders.

Conclusion: Gut bacteria that produce short-chain fatty acids, such as Roseburia and Faecalibacterium, could be less abundant in patients with psychiatric disorders, while commensal genera, for example Bifidobacterium, might be more abundant compared to healthy controls. However, most included studies were hampered by methodological shortcomings including small sample size, unclear diagnostics, failure to address confounding factors, and inadequate bio-informatic processing, which might contribute to inconsistent results. Based on our findings, we forward recommendations to improve quality and comparability of future microbiota studies in psychiatry.
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http://dx.doi.org/10.1097/PSY.0000000000000959DOI Listing
June 2021

Oxygen defective titanate nanotubes induced by iron deposition for enhanced peroxymonosulfate activation and acetaminophen degradation: Mechanisms, water chemistry effects, and theoretical calculation.

J Hazard Mater 2021 May 27;418:126180. Epub 2021 May 27.

The Key Laboratory of Water and Sediment Sciences, Ministry of Education, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China; State Environmental Protection Key Laboratory of All Material Fluxes in River Ecosystems, Peking University, Beijing 100871, China.

The large consumption of acetaminophen (APAP) worldwide and unsatisfactory treatment efficiencies by conventional wastewater treatment processes give rise to the seeking of new technology for its effective removal. Herein, we proposed a facile one-step hydrothermal method to synthesize defective iron deposited titanate nanotubes (Fe/TNTs) for peroxymonosulfate (PMS) activation and APAP degradation. The retarded first-order reaction rate of APAP degradation by Fe/TNTs was 5.1 times higher than that of neat TNTs. Characterizations indicated iron deposition effectively induced oxygen vacancies and Ti, facilitating the electrical conductivity and PMS binding affinity of Fe/TNTs. Besides, oxygen vacancies could act as an electron mediator through PMS activation by iron. Moreover, the formation of Fe-O-Ti bond facilitated the synergistic redox coupling between Fe and Ti, further enhancing the PMS activation. SO was the major radical, causing C-N bond cleavage and decreasing the overall toxicity. In contrast, APAP degradation by neat TNTs-PMS system mainly works through nonradical reaction. The Fe/TNTs activated PMS showed desired APAP removal under mild water chemistry conditions and good reusability. This work is expected to expand the potential application of titanate nanomaterials for PMS activation, and shed light on facile synthesis of oxygen defective materials for sulfate-radical-based advanced oxidation processes.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126180DOI Listing
May 2021

Serum calprotectin as a prognostic predictor in severe traumatic brain injury.

Clin Chim Acta 2021 Jun 6;520:101-107. Epub 2021 Jun 6.

Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, China. Electronic address:

Background: Calprotectin plays an important role during inflammation. We intended to explore the prognostic value of serum calprotectin levels in patients with severe traumatic brain injury (sTBI).

Methods: In this prospective cohort study of 149 sTBI patients, we determined the relationship between serum calprotectin levels and 90-day overall survival plus poor outcome (Glasgow outcome scale score of 1-3) after sTBI, and analyzed its associations with Rotterdam computerized tomography (CT) scores, Glasgow coma scale (GCS) scores and two markers of inflammatory reaction including serum C-reactive protein levels and blood leucocyte count.

Results: Serum calprotectin levels were significantly correlated with Rotterdam CT scores, GCS scores, serum C-reactive protein levels and blood leucocyte count. Patients with poor outcome at 90 days displayed higher serum calprotectin levels than the other remainders. Serum calprotectin appeared as an independent predictor for 90-day overall survival and poor outcome. Under receiver operating characteristic curve, serum calprotectin levels exhibited an efficient discrimination capacity for 90-day poor outcome.

Conclusions: Serum calprotectin levels are significantly correlated with inflammation, trauma severity and poor outcome at 90 days in sTBI patients, suggesting that serum calprotectin may be a biomarker for providing complementary prognostic information to identify patients at risk of poor outcome after sTBI.
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http://dx.doi.org/10.1016/j.cca.2021.06.009DOI Listing
June 2021

Genome-wide identification and expression analysis of the bHLH transcription factor family and its response to abiotic stress in sorghum [Sorghum bicolor (L.) Moench].

BMC Genomics 2021 Jun 5;22(1):415. Epub 2021 Jun 5.

College of Agriculture, Guizhou University, Huaxi District, Guiyang City, 550025, Guizhou Province, P.R. China.

Background: Basic helix-loop-helix (bHLH) is a superfamily of transcription factors that is widely found in plants and animals, and is the second largest transcription factor family in eukaryotes after MYB. They have been shown to be important regulatory components in tissue development and many different biological processes. However, no systemic analysis of the bHLH transcription factor family has yet been reported in Sorghum bicolor.

Results: We conducted the first genome-wide analysis of the bHLH transcription factor family of Sorghum bicolor and identified 174 SbbHLH genes. Phylogenetic analysis of SbbHLH proteins and 158 Arabidopsis thaliana bHLH proteins was performed to determine their homology. In addition, conserved motifs, gene structure, chromosomal spread, and gene duplication of SbbHLH genes were studied in depth. To further infer the phylogenetic mechanisms in the SbbHLH family, we constructed six comparative syntenic maps of S. bicolor associated with six representative species. Finally, we analyzed the gene-expression response and tissue-development characteristics of 12 typical SbbHLH genes in plants subjected to six different abiotic stresses. Gene expression during flower and fruit development was also examined.

Conclusions: This study is of great significance for functional identification and confirmation of the S. bicolor bHLH superfamily and for our understanding of the bHLH superfamily in higher plants.
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http://dx.doi.org/10.1186/s12864-021-07652-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178921PMC
June 2021

Difficult biliary cannulation in ERCP procedures with or without trainee involvement: a comparison study.

Endoscopy 2021 Jun 4. Epub 2021 Jun 4.

Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Aims 5-5-1 criteria have been proposed by the European Society of Gastrointestinal Endoscopy to define difficult ERCP cannulation. However, the criteria may be inappropriate for cannulation procedures with trainee involvement. Here we aimed to develop difficult cannulation criteria in trainee involved cannulation. Methods Patients undergoing biliary cannulation with (trainee group) or without trainee involvement (non-trainee group) were eligible. The procedures which might be too easy (e.g. fistula) or too difficult (e.g. altered anatomy) was excluded. The primary outcome was difficult cannulation, which was defined as the values of cannulation time, attempts, or inadvertent PD cannulation exceeding 75% percentile of each variable. Propensity score matching analysis was used. Results After PSM, there were 1596 patients in each group. The trainee group had longer median cannulation time [7.5 (2.2-15.3) min vs. 2.0 (0.6-5.2) min], more median attempts [5 (2-10) vs. 2 (1-4)] and median inadvertent PD cannulation [0 (0-2) vs. 0 (0-1)] compared with the non-trainee group (all p<0.001). 15-10-2 and 5-5-1 difficult cannulation criteria determined by exceeding 75% percentile of cannulation variables were proposed for trainee involved cannulation and were nearly confirmed for non-trainee involved cannulation, respectively. The proportion of difficult cannulation was 35.5% 95%CI [33.2%, 37.9%] and 31.8% 95%CI [29.5%, 34.2%] respectively (OR 1.18 95%CI [1.02-1.37]). The incidence of PEP (7.8% 95%CI [5.7%, 10.3%] vs. 9.8% 95%CI [7.4%, 12.8%]) in difficult patients were comparable. Conclusion By using 75% percentiles of cannulation-related variables as cutoff values, we proposed that 15-10-2 difficult cannulation criteria could be appropriate in trainee involved cannulation.
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http://dx.doi.org/10.1055/a-1523-0780DOI Listing
June 2021

[Retracted] Knockdown of PREX2a inhibits the malignant phenotype of glioma cells.

Mol Med Rep 2021 Aug 3;24(2). Epub 2021 Jun 3.

Department of Neurosurgery, People's Hospital of Ningxiang County, Changsha, Hunan 410600, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that cell invasion assay data in the article (featured in Fig. 4A) were strikingly similar to data appearing in different form in another article by different authors at different research institutions, which had already been published elsewhere at the time of the present article's submission. Furthermore, flow cytometric data featured in Fig. 2D were strikingly similar to those in another previously published paper, and cell cyle data included in Fig. 3 had apparently previously published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors also expressed their intention to retract the paper on the grounds that the corresponding author and several of the authors failed to confirm the approval of the final version of the manuscript. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on 13: 2301‑2307, 2016; DOI: 10.3892/mmr.2016.4799].
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http://dx.doi.org/10.3892/mmr.2021.12184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185513PMC
August 2021

A novel decision tree model based on chromosome imbalances in cell-free DNA and CA-125 in the differential diagnosis of ovarian cancer.

Int J Biol Markers 2021 May 31:1724600821992356. Epub 2021 May 31.

Department of Gynecology, Qingdao Municipal Hospital, Qingdao, Shandong Province, China.

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors.

Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled.

Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy (<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975.

Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.
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http://dx.doi.org/10.1177/1724600821992356DOI Listing
May 2021

Frequency Principle in Broad Learning System.

IEEE Trans Neural Netw Learn Syst 2021 May 28;PP. Epub 2021 May 28.

Deep neural networks have achieved breakthrough improvement in various application fields. Nevertheless, they usually suffer from a time-consuming training process because of the complicated structures of neural networks with a huge number of parameters. As an alternative, a fast and efficient discriminative broad learning system (BLS) is proposed, which takes the advantages of flat structure and incremental learning. The BLS has achieved outstanding performance in classification and regression problems. However, the previous studies ignored the reason why the BLS can generalize well. In this article, we focus on the interpretation from the viewpoint of the frequency domain. We discover the existence of the frequency principle in BLS, i.e., the BLS preferentially captures low-frequency components quickly and then fits the high frequencies during the incremental process of adding feature nodes and enhancement nodes. The frequency principle may be of great inspiration for expanding the application of BLS.
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http://dx.doi.org/10.1109/TNNLS.2021.3081568DOI Listing
May 2021

Pyrrole-Based Conjugated Microporous Polymers as Efficient Heterogeneous Catalysts for Knoevenagel Condensation.

Front Chem 2021 10;9:687183. Epub 2021 May 10.

Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Science, Tianjin University, Tianjin, China.

Conjugated microporous polymers (CMPs) with robust architectures, facilely tunable pore sizes and large specific surface areas have emerged as an important class of porous materials due to their demonstrated prospects in various fields, e.g. gas storage/separation and heterogeneous catalysis. Herein, two new pyrrole-based CMPs with large specific surface areas and good stabilities were successfully prepared by one-step oxidative self-polycondensation of 1,2,4,5-tetra (pyrrol-2-ly)benzene or 1,3,5-tri (pyrrol-2-ly)benzene, respectively. Interestingly, both CMPs showed very high catalytic activity toward Knoevenagel condensation reaction, which was attributed to the inherent pore channels, high specific surface areas and abundant nitrogen sites within CMPs. Additionally, both CMPs displayed excellent recyclability with negligible degradation after 10 cycles. This work provides new possibilities into designing novel nitrogen-rich high-performance heterogeneous catalysts.
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http://dx.doi.org/10.3389/fchem.2021.687183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141711PMC
May 2021

DLnet With Training Task Conversion Stream for Precise Semantic Segmentation in Actual Traffic Scene.

IEEE Trans Neural Netw Learn Syst 2021 May 25;PP. Epub 2021 May 25.

Many successful semantic segmentation models trained on certain datasets experience a performance gap when they are applied to the actual scene images, expressing weak robustness of these models in the actual scene. The training task conversion (TTC) and domain adaption field have been originally proposed to solve the performance gap problem. Unfortunately, many existing models for TTC and domain adaptation have defects, and even if the TTC is completed, the performance is far from the original task model. Thus, how to maintain excellent performance while completing TTC is the main challenge. In order to address this challenge, a deep learning model named DLnet is proposed for TTC from the existing image dataset-based training task to the actual scene image-based training task. The proposed network, named the DLnet, contains three main innovations. The proposed network is verified by experiments. The experimental results show that the proposed DLnet not only can achieve state-of-the-art quantitative performance on four popular datasets but also can obtain outstanding qualitative performance in four actual urban scenes, which demonstrates the robustness and performance of the proposed DLnet. In addition, although the proposed DLnet cannot achieve outstanding performance in real time, it can still achieve a moderate performance in real time, which is within an acceptable range.
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http://dx.doi.org/10.1109/TNNLS.2021.3080261DOI Listing
May 2021

Global health effects of future atmospheric mercury emissions.

Nat Commun 2021 05 24;12(1):3035. Epub 2021 May 24.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, P. R. China.

Mercury is a potent neurotoxin that poses health risks to the global population. Anthropogenic mercury emissions to the atmosphere are projected to decrease in the future due to enhanced policy efforts such as the Minamata Convention, a legally-binding international treaty entered into force in 2017. Here, we report the development of a comprehensive climate-atmosphere-land-ocean-ecosystem and exposure-risk model framework for mercury and its application to project the health effects of future atmospheric emissions. Our results show that the accumulated health effects associated with mercury exposure during 2010-2050 are $19 (95% confidence interval: 4.7-54) trillion (2020 USD) realized to 2050 (3% discount rate) for the current policy scenario. Our results suggest a substantial increase in global human health cost if emission reduction actions are delayed. This comprehensive modeling approach provides a much-needed tool to help parties to evaluate the effectiveness of Hg emission controls as required by the Minamata Convention.
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http://dx.doi.org/10.1038/s41467-021-23391-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144432PMC
May 2021

, a new executor gene that confers durable and broad-spectrum resistance to bacterial blight disease in rice.

Plant Commun 2021 May 9;2(3):100143. Epub 2021 Jan 9.

College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, China.

Bacterial blight (BB) is a globally devastating rice disease caused by pv. (). The use of disease resistance () genes in rice breeding is an effective and economical strategy for the control of this disease. Nevertheless, a majority of genes lack durable resistance for long-term use under global warming conditions. Here, we report the isolation of a novel executor gene, , that confers extremely durable, broad-spectrum, and heat-tolerant resistance to . The expression of was induced by incompatible strains that secreted the transcription activator-like effector (TALE) AvrXa7 or PthXo3, which recognized effector binding elements (EBEs) in the promoter. Furthermore, induction was faster and stronger under high temperatures. Overexpression of or co-transformation of with triggered a hypersensitive response in plants. Constitutive expression of activated a defense response in the absence of but inhibited the growth of transgenic rice plants. In addition, analysis of over 3000 rice varieties showed that the locus was found primarily in the and subgroups. A variation consisting of an 11-bp insertion and a base substitution (G to T) was found in in the tested varieties, resulting in a loss of BB resistance. Through a decade of effort, we have identified an important BB resistance gene and characterized its distinctive interaction with strains; these findings will greatly facilitate research on the molecular mechanism of -mediated resistance and promote the use of this valuable gene in breeding.
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http://dx.doi.org/10.1016/j.xplc.2021.100143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132130PMC
May 2021

Cadmium Impairs Autophagy Leading to Apoptosis by Ca-Dependent Activation of JNK Signaling Pathway in Neuronal Cells.

Neurochem Res 2021 May 22. Epub 2021 May 22.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Chixia District, Nanjing, 210023, People's Republic of China.

Autophagy, a process for self-degradation of intracellular components and dysfunctional organelles, is closely related with neurodegenerative diseases. It has been shown that cadmium (Cd) induces neurotoxicity partly by impairing autophagy. However, the underlying mechanism is not fully elucidated. In this study, we show that Cd induced expansion of autophagosomes with a concomitant abnormal expression of autophagy-related (Atg) proteins in PC12 cells and primary murine neurons. 3-MA, a classical inhibitor of autophagy, attenuated Cd-induced expansion of autophagosomes and apoptosis in the cells. Further investigation demonstrated that Cd activated JNK pathway contributing to autophagosome expansion-dependent neuronal apoptosis. This is supported by the findings that pharmacological inhibition of JNK with SP600125 or expression of dominant negative c-Jun markedly attenuated Cd-induced expansion of autophagosomes and abnormal expression of Atg proteins, as well as apoptosis in PC12 cells and/or primary neurons. Furthermore, we noticed that chelating intracellular free Ca ([Ca]) with BAPTA/AM profoundly blocked Cd-elicited activation of JNK pathway and consequential expansion of autophagosomes, abnormal expression of Atg proteins, and apoptosis in the neuronal cells. Similar events were also seen following prevention of [Ca] elevation with EGTA or 2-APB, implying a Ca-dependent mechanism involved. Taken together, the results indicate that Cd impairs autophagy leading to apoptosis by Ca-dependent activation of JNK signaling pathway in neuronal cells. Our findings highlight that manipulation of intracellular Ca level and/or JNK activity to ameliorate autophagy may be a promising intervention against Cd-induced neurotoxicity and neurodegeneration.
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http://dx.doi.org/10.1007/s11064-021-03341-xDOI Listing
May 2021

Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.

Int Immunopharmacol 2021 May 15;96:107771. Epub 2021 May 15.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, PR China. Electronic address:

B-cell activating factor (BAFF) is an essential cytokine for B-cell maturation, differentiation and survival, and excess BAFF induces aggressive or neoplastic B-cell disorders and contributes to development of autoimmune diseases. Metformin, an anti-diabetic drug, has recently garnered a great attention due to its anti-proliferative and immune-modulatory features. However, little is known regarding the effect of metformin on BAFF-stimulated B cells. Here, we show that metformin attenuated human soluble BAFF (hsBAFF)-induced cell proliferation and survival by blocking the Erk1/2 pathway in normal and B-lymphoid (Raji) cells. Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin's inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin. Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin's suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved. Furthermore, we noticed that metformin hindered hsBAFF-activated mTOR pathway in B cells. Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin's suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability. These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells. Our findings support that metformin has a great potential for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.
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http://dx.doi.org/10.1016/j.intimp.2021.107771DOI Listing
May 2021

Donor-Acceptor Type Covalent Organic Frameworks.

Chemistry 2021 May 18. Epub 2021 May 18.

Department of Chemistry and Tianjin Key Laboratory of Molecular Optoelectronic Science, Tianjin University, Tianjin, 300072, P. R. China.

Intermolecular charge transfer (ICT) effect has been widely studied in both small molecules and linear polymers. Covalently-bonded donor-acceptor pairs with tunable bandgaps and photoelectric properties endow these materials with potential applications in optoelectronics, fluorescent bioimaging, and sensors, etc. However, owing to the lack of charge transfer pathway or effective separation of charge carriers, unfavorable charge recombination gives rise to inevitable energy loss. Covalent organic frameworks (COFs) can be mediated with various geometry- and property-tailored building blocks, where donor (D) and acceptor (A) segments are connected by covalent bonds and can be finely arranged to form highly ordered networks (namely D-A COFs). The unique structural features of D-A COFs render the formation of segregated D-A stacks, thus provides pathways and channels for effective charge carriers transport. This review highlights the significant progress on D-A COFs over the past decade with emphasis on design principles, growing structural diversities, and promising application potentials.
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http://dx.doi.org/10.1002/chem.202101135DOI Listing
May 2021

A method of 3D-3D multi-stage non-rigid registration of the spine based on binocular structured light.

Int J Med Robot 2021 May 17:e2283. Epub 2021 May 17.

School of Mechanical and Electrical Engineering, Soochow University, Suzhou, China.

Background: Intraoperative deformation and radiation are common problems in spinal surgery. A three-dimensional multi-stage dynamic iterative non-rigid registration method of the spine based on binocular structured light is proposed in this paper to overcome these problems.

Method: The problem of intraoperative radiation in traditional X-ray and CT is overcome by using binocular structured light. A three-dimensional spinal mask based on binary code is designed to reduce the influence of non-interested regions on the operation. Principal component analysis (PCA) algorithm is used to complete the rough registration between the preoperative CT model of the spine and the reconstructed surface of the intraoperative structured light. A new framework of multi-stage dynamic iterative non-rigid registration of the spine is proposed. The Iterative Closest Point (ICP) algorithm based on bidirectional selection is proposed to complete the single-stage registration of the spine. Then the multi-stage dynamic iterative registration of the spine is completed to solve the problem of large registration error caused by the deformation of the spine.

Results: The method proposed in this paper is compared with traditional registration methods, and its application is verified experimentally. The results show that the registration accuracy and time of the proposed method are  mm and  s, respectively. The accuracy of the method is 81.5% and 78.2% higher than that of the contour method and the method of marker points, respectively.

Conclusions: The method can effectively avoid intraoperative radiation, reduce the registration error caused by the deformation of the spine, and has a high practicability.
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http://dx.doi.org/10.1002/rcs.2283DOI Listing
May 2021

Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

Nature 2021 Jun 17;594(7861):33-36. Epub 2021 May 17.

Key Laboratory of Particle Astrophysics & Experimental Physics Division & Computing Center, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
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http://dx.doi.org/10.1038/s41586-021-03498-zDOI Listing
June 2021

Model for the prediction of mechanical asphyxia as the cause of death based on four biological indexes in human cardiac tissue.

Sci Justice 2021 May 4;61(3):221-226. Epub 2021 Mar 4.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

Determination of mechanical asphyxia as the cause of death has always been difficult for forensic pathologists, particularly when signs of asphyxia are not obvious on the body. Currently, depending on only physical examination of corpses, pathologists must be cautious when making cause-of-death appraisals. In a previous study, four biomarkers-dual-specificity phosphatase 1 (DUSP1), potassium voltage-gated channel subfamily J member 2 (KCNJ2), miR-122, and miR-3185-were screened in human cardiac tissue from cadavers that died from mechanical asphyxia compared with those that died from craniocerebral injury, hemorrhagic shock, or other causes. Expression of the markers correlated with death from mechanical asphyxia regardless of age, environmental temperature, and postmortem interval. However, a single biological index is not an accurate basis for the identification of the cause of death. In this study, receiver operating characteristic curves of the ΔCq values of the four indexes were generated. The diagnostic accuracy of the indexes was judged according to their area under the curve (DUSP1: 0.773, KCNJ2: 0.775, miR-122: 0.667, and miR-3185: 0.801). Finally, a nomogram was generated, and single blind experiment was conducted to verify the cause of death of mechanical asphyxia.
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http://dx.doi.org/10.1016/j.scijus.2021.02.003DOI Listing
May 2021

Hydrological management affected dissolved organic matter chemistry and organic carbon burial in the Three Gorges Reservoir.

Water Res 2021 Jul 29;199:117195. Epub 2021 Apr 29.

Organic Geochemistry Unit, Key Laboratory of Geoscience Big Data and Deep Resource of Zhejiang Province, School of Earth Sciences, Zhejiang University, Hangzhou, 310027, China. Electronic address:

With the linkage between dissolved organic matter (DOM) and the characteristics of natural ecosystem assessed extensively, the properties of DOM in reservoirs, the typical human interrupted ecosystems, have been focused on in recent years, which is critical for the understanding of human impacts on watershed ecosystems and carbon cycling. This study aims to analyze the effect of hydrological management on the DOM chemistry and organic carbon burial in Daning River tributary of the world's largest Three Gorges Reservoir (TGR). Based on the application of a combined approach including bulk geochemical analyses, optical spectroscopy, and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry, various sources of DOM (terrestrial, anthropogenic, and autochthonous sources) were revealed. An increasing trend of terrestrial and recalcitrant DOM was observed along the upstream to downstream transect of Daning River tributary, which was mainly caused by the water intrusion with a higher terrestrial and recalcitrant signature from mainstream to tributary resulted from hydrological management of TGR. Integrated with the analysis of sedimentary organic matter in Daning River tributary in the past decade (after the construction of TGR), our work suggests that organic carbon burial in the reservoir could be enhanced by hydrological management-induced variation in DOM chemistry. Further studies are needed to better constrain the effects of damming reservoirs on carbon cycling considering their booming all over the world.
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http://dx.doi.org/10.1016/j.watres.2021.117195DOI Listing
July 2021

Dietary supplementation with daidzein and Chinese herbs, independently and combined, improves laying performance, egg quality and plasma hormone levels of post-peak laying hens.

Poult Sci 2021 Jun 12;100(6):101115. Epub 2021 Mar 12.

Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou, Jiangsu Province, PR China, 225125; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou, Jiangsu Province, PR China, 225009. Electronic address:

This experiment examined the separate and combined effects of daidzein (Da) and Chinese herbs (CH) on laying performance and egg quality of post-peak laying hens. Additionally, we explored potential mechanisms of action for these 2 additives by examining plasma hormone levels. After 4 wk of acclimation to caging, 60-week-old Hyline Brown hens (360) were selected and randomly divided into 4 groups with 6 replicates and 15 chickens per replicate. The following 4 dietary groups were utilized: 1) control group (basal diet); 2) Da group (basal diet + 0.03 kg/t DA); 3) CH group (basal diet +0.6 kg/t CH); 4) Da + CH group (basal diet + 0.03 kg/t Da + 0.6 kg/t CH). Data were analyzed in a completely randomized design with a 2×2 factorial arrangement of treatments. Egg production and FCR treatment averages were analyzed in the following 3 phases: wk 1-4, 5-8, and 1-8 of treatment administration. Results revealed that Da increased egg production but decreased FCR (P < 0.05) for wk 1-8 and especially during wk 5-8 (P < 0.05). CH decreased FCR in wk 1-4 and 5-8 (P < 0.05), but increased egg production only during wk 5-8 (P < 0.05). Da increased Haugh units (P < 0.05) on wk 4 and 8; CH increased Haugh units (P < 0.05) but decreased yolk ratio (P < 0.05) on wk 4 and 8. Da increased the plasma levels of T3, PROG, FSH, LH and E2 (P < 0.05); CH increased the plasma level of T3 (P < 0.05). Additionally, Da x CH interactions existed for albumen height, Haugh units, albumen ratio and the level of T3 on wk 8 (P < 0.05), indicating that the combination of Da and CH was more effective than administration of either of these dietary components independently. In conclusion, Da and CH, both independently and in combination, increase laying performance, egg quality and plasma hormones levels in post-peak laying hens. Therefore, these treatments may be able to provide prolonged economic benefits to aged laying hens.
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http://dx.doi.org/10.1016/j.psj.2021.101115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131741PMC
June 2021

Fluorinated interphase enables reversible aqueous zinc battery chemistries.

Nat Nanotechnol 2021 May 10. Epub 2021 May 10.

Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, USA.

Metallic zinc is an ideal anode due to its high theoretical capacity (820 mAh g), low redox potential (-0.762 V versus the standard hydrogen electrode), high abundance and low toxicity. When used in aqueous electrolyte, it also brings intrinsic safety, but suffers from severe irreversibility. This is best exemplified by low coulombic efficiency, dendrite growth and water consumption. This is thought to be due to severe hydrogen evolution during zinc plating and stripping, hitherto making the in-situ formation of a solid-electrolyte interphase (SEI) impossible. Here, we report an aqueous zinc battery in which a dilute and acidic aqueous electrolyte with an alkylammonium salt additive assists the formation of a robust, Zn-conducting and waterproof SEI. The presence of this SEI enables excellent performance: dendrite-free zinc plating/stripping at 99.9% coulombic efficiency in a Ti||Zn asymmetric cell for 1,000 cycles; steady charge-discharge in a Zn||Zn symmetric cell for 6,000 cycles (6,000 h); and high energy densities (136 Wh kg in a Zn||VOPO full battery with 88.7% retention for >6,000 cycles, 325 Wh kg in a Zn||O full battery for >300 cycles and 218 Wh kg in a Zn||MnO full battery with 88.5% retention for 1,000 cycles) using limited zinc. The SEI-forming electrolyte also allows the reversible operation of an anode-free pouch cell of Ti||ZnVOPO at 100% depth of discharge for 100 cycles, thus establishing aqueous zinc batteries as viable cell systems for practical applications.
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http://dx.doi.org/10.1038/s41565-021-00905-4DOI Listing
May 2021

The effect of sacrificing the posterior cruciate ligament on total knee arthroplasty with cruciate retaining highly congruent rotating platform prosthesis.

J Orthop Surg Res 2021 May 7;16(1):299. Epub 2021 May 7.

Department of Orthopedics, Fujian Provincial Hospital, Fuzhou, 350000, China.

Objective: To analyze the effect of sacrificing the posterior cruciate ligament (PCL) on the early postoperative outcome of cruciate retaining (CR) highly congruent rotating platform TKA.

Methods: From May 2018 to September 2019, 105 cases of total knee arthroplasty (TKA) with CR highly congruent rotating platform prosthesis were retrospectively analyzed. According to the tension of posterior cruciate ligament, they were divided into sacrifice group (29 cases, 27.6%) and retention group (76 cases, 72.4%). Preoperative and postoperative The Hospital for Special Surgery (HSS) score, range of motion (ROM) were compared between the two groups. In addition, postoperative infection, prosthesis loosening, bearing dislocation, and other complications were also compared.

Results: All patients were followed up for 11~24 months (mean 18.14 ± 3.52) months. There was no significant difference in general data, preoperative HSS score, and ROM between the two groups (P > 0.05). At the last follow-up, HSS score and ROM of the two groups were better than those before operation (P < 0.05). However, there was no significant difference between the two groups (P > 0.05). Moreover, there were no complications such as infection, loosening of prosthesis, and bearing dislocation in all cases.

Conclusion: In CR, highly congruent rotating platform TKA with or without tension of the PCL can achieve satisfactory outcomes. Tension-free PCL do not cause joint instability.
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http://dx.doi.org/10.1186/s13018-021-02433-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103609PMC
May 2021

Negative-tone molecular glass photoresist for high-resolution electron beam lithography.

R Soc Open Sci 2021 Mar 3;8(3):202132. Epub 2021 Mar 3.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Photochemistry, Institute of Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

A low molecular weight organic compound containing bis-phenol A backbone (BPA-6OH) is reported as a negative-tone photoresist. This material has a high glass transition temperature and excellent thermal stability. A good contrast, well-resolved line pattern around 73.4 nm and sensitivity of 52 µC cm can be received for negative-tone molecular glass photoresist upon exposure in electron beam lithography system. It indicates that the negative-tone molecular glass photoresist is one of the promising candidates for use in electron beam lithography.
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http://dx.doi.org/10.1098/rsos.202132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074933PMC
March 2021

Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4.

Aging Cell 2021 Jun 6;20(6):e13370. Epub 2021 May 6.

Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.

Research on ageing-associated genes is important for investigating ageing and anti-ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3-HDAC complex and inhibits its deacetylated activity, leads to hyper-acetylation of the histones at the promoters of mTOR-related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing-associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.
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http://dx.doi.org/10.1111/acel.13370DOI Listing
June 2021

miR-373-3p inhibits epithelial-mesenchymal transition via regulation of TGFβR2 in choriocarcinoma.

J Obstet Gynaecol Res 2021 May 5. Epub 2021 May 5.

Department of Pathology, Chengde Medical University, Chengde, Hebei, China.

Aim: Previous studies have indicated that early metastasis is a major cause of mortality in patients with choriocarcinoma. However, what determines whether early metastasis of choriocarcinoma has occurred is unknown. The emerging role of miRNA in regulating cancer development and progression has been recognized. miR-373 has been shown to play pivotal roles in tumorigenesis and metastasis. However, whether miR-373 functions to promote choriocarcinoma metastasis is not clear. The purpose of this study is to determine the function of miR-373-3p in the progression of this cancer.

Methods: In this study, we first compared epithelial-mesenchymal transition (EMT)-related markers, which were inversely correlated with miR-373-3p expression in trophoblast and choriocarcinoma cell lines. Using PCR and Western blot, upregulation of miR-373-3p was observed to inhibit EMT progression. Similarly, gain- and loss-of-function studies revealed that ectopic miR-373-3p overexpression inhibited the migration by transwell methods of choriocarcinoma cells.

Results: Our results revealed that miR-373-3p acted as an EMT inhibitor in JEG-3 and JAR cells; this was due to its mediation of the transforming growth factor-β (TGFβ) signaling pathway, which was responsible for EMT. miRNA microarray analysis demonstrated that miR-373-3p interacted with the 3' untranslated region of TGFβR2 mRNA, and then Western blot and dual-luciferase reporter gene assays verified this interaction.

Conclusion: Our findings suggest that miR-373-3p upregulation partly accounts for TGFβR2 downregulation and leads to a restraint of EMT and migration. miR-373-3p may therefore serve as a valuable potential target in the treatment of choriocarcinoma.
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http://dx.doi.org/10.1111/jog.14809DOI Listing
May 2021

Establishment and Verification of a Prediction Model for Symptomatic Radiation Pneumonitis in Patients with Esophageal Cancer Receiving Radiotherapy.

Med Sci Monit 2021 May 6;27:e930515. Epub 2021 May 6.

Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China (mainland).

BACKGROUND This study aimed to determine the value of the significant index in predicting symptomatic radiation pneumonitis (RP) in esophageal cancer patients, establish a nomogram prediction model, and verify the model. MATERIAL AND METHODS The patients enrolled were divided into 2 groups: a model group and a validation group. According to the logistic regression analysis, the independent predictors for symptomatic RP were obtained, and the nomogram prediction model was established according to these independent predictors. The consistency index (C-index) and calibration curve were used to evaluate the accuracy of the model, and the prediction ability of the model was verified in the validation group. Recursive partitioning analysis (RPA) was used for the risk stratification analysis. RESULTS The ratio of change regarding the pre-albumin at the end of treatment (P=0.001), platelet-to-lymphocyte ratio during treatment (P=0.027), and neutrophil-to-lymphocyte ratio at the end of treatment (P=0.001) were the independent predictors for symptomatic RP. The C-index of the nomogram model was 0.811. According to the risk stratification of RPA, the whole group was divided into 3 groups: a low-risk group, a medium-risk group, and a high-risk group. The incidence of symptomatic RP was 0%, 16.9%, and 57.6%, respectively. The receiver operating characteristic curve also revealed that the nomogram model has good accuracy in the validation group. CONCLUSIONS The developed nomogram and corresponding risk classification system have superior prediction ability for symptomatic RP and can predict the occurrence of RP in the early stage.
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http://dx.doi.org/10.12659/MSM.930515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112075PMC
May 2021