Publications by authors named "Kun Chen"

769 Publications

Orchestration of plant development and defense by indirect crosstalk of SA and BR signaling through a transcription factor GhTINY2.

J Exp Bot 2021 Apr 30. Epub 2021 Apr 30.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, Hubei, China.

Salicylic acid (SA) and brassinosteroids (BRs) are well known to regulate diverse processes of plant development and stress responses, but the mechanisms by which these phytohormones mediate the growth-defense trade-off is largely unclear. In addition, little is known about the roles of DEHYDRATION RESPONSIVE ELEMENT BINDING (DREB) transcription factors, especially in biotic stress and plant growth. Here, we identified a cotton (Gossypium hirsutum) APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) gene GhTINY2 which is strongly induced by Verticillium dahliae. Overexpression of GhTINY2 in cotton and Arabidopsis (Arabidopsis thaliana) enhanced tolerance to V. dahliae, while knockdown of GhTINY2 expression increased cotton susceptibility to the pathogen. By directly activating WRKY51 expression, GhTINY2 promoted SA accumulation and SA signaling transduction. Moreover, GhTINY2-overexpressing cotton and Arabidopsis showed growth retardation, increased sensitivity to inhibitors of BR biosynthesis and downregulation of several BR-induced genes and upregulation of BR-repressed genes, while GhTINY2-RNAi cotton showed the opposite results. We further demonstrate that GhTINY2 negatively regulates BR signaling by interacting with BRASSINAZOLE-RESISTANT 1 (BZR1) and restraining its transcriptional activation of the expression of INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19). These findings indicate that GhTINY2 fine-tunes the immunity-growth trade-off via an indirect crosstalk between WRKY51-mediated SA biosynthesis and BZR1-IAA19-regulated BR signaling.
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http://dx.doi.org/10.1093/jxb/erab186DOI Listing
April 2021

Research on Channel Selection and Multi-Feature Fusion of EEG Signals for Mental Fatigue Detection.

Entropy (Basel) 2021 Apr 13;23(4). Epub 2021 Apr 13.

School of Information Engineering, Wuhan University of Technology, Wuhan 430070, China.

With the rapid development of modern social science and technology, the pace of life is getting faster, and brain fatigue has become a sub-health state that seriously affects the normal life of people. Electroencephalogram (EEG) signals reflect changes in the central nervous system. Using EEG signals to assess mental fatigue is a research hotspot in related fields. Most existing fatigue detection methods are time-consuming or don't achieve satisfactory results due to insufficient features extracted from EEG signals. In this paper, a 2-back task is designed to induce fatigue. The weight value of each channel under a single feature is calculated by ReliefF algorithm. The classification accuracy of each channel under the corresponding features is analyzed. The classification accuracy of each single channel is combined to perform weighted summation to obtain the weight value of each channel. The first half channels sorted in descending order based on the weight value is chosen as the common channels. Multi-features in frequency and time domains are extracted from the common channel data, and the sparse representation method is used to perform feature fusion to obtain sparse fused features. Finally, the SRDA classifier is used to detect the fatigue state. Experimental results show that the proposed methods in our work effectively reduce the number of channels for computation and also improve the mental fatigue detection accuracy.
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http://dx.doi.org/10.3390/e23040457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069717PMC
April 2021

Detection of Epstein-Barr virus encoded RNA in fixed cells and tissues using CRISPR/Cas-mediated RCasFISH.

Anal Biochem 2021 Apr 26:114211. Epub 2021 Apr 26.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, P. R. China; Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, 100730, P. R. China. Electronic address:

Identification of Epstein-Barr virus (EBV)-infected cells is critical for the diagnosis and clinical management of EBV-associated diseases. EBV-encoded RNA (EBER) located in the nucleus is a reliable marker due to its high levels of expression and inherent stability in tissue specimens. EBER in situ hybridization has long been the gold standard for detecting tumor-associated latent EBV infection and is valuable in determining the primary site and radiation fields of EBV-related malignancies. However, reliable detection is somewhat restricted by diffused signal and time-consuming procedure of this method, especially when proteins and RNA needed to be labeled simultaneously. Here, we optimized and validated our CRISPR-dCas9 mediated in situ RNA imaging tool-RCasFISH that enabled us to detect EBER rapidly and was compatible with IHC methods in fixed cells and tissue sections. Our approach could provide an attractive alternative for the molecular diagnosis of latent EBV infection.
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http://dx.doi.org/10.1016/j.ab.2021.114211DOI Listing
April 2021

Transcriptomic responses predict the toxic effect of parental co-exposure to dibutyl phthalate and diisobutyl phthalate on the early development of zebrafish offspring.

Aquat Toxicol 2021 Apr 16;235:105838. Epub 2021 Apr 16.

School of the Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.

Dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) have been reported to exhibit reproductive toxicity in vertebrates. However, the combined effect of DBP and DiBP on offspring of exposed parents remains unclear, especially for aquatic organisms such as fish. The aims of this study were to assess the effects of parental co-exposure to DBP and DiBP on early development of zebrafish offspring, and to explore the potential molecular mechanisms involved. The early developmental indicators and transcriptomic profiles of F1 larvae were examined after parental exposure to DBP, DiBP and their mixtures (Mix) for 30 days. Results showed that parental exposure to DBP and DiBP, alone or in combination, resulted in increased hatchability at 48 hpf and heart rate at 96 hpf, and increased the prevalence of malformations and mortality in F1 larvae. Generalized linear model (GLM) suggested an antagonistic interactive effect between DBP and DiBP on mortality and malformations of F1 larvae. The transcriptomic analysis revealed that the molecular mechanisms of parental co-exposure were different from those of either chemical alone. Disruption of molecular functions involved unfolded protein binding, E-box binding and photoreceptor activity in F1 larvae. These findings provide initial insights in the potential mechanism of action of parental co-exposure to DBP and DiBP.
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http://dx.doi.org/10.1016/j.aquatox.2021.105838DOI Listing
April 2021

Effect of COVID-19 on Hospital Visits in Ningbo, China: An Interrupted Time Series Analysis.

Int J Qual Health Care 2021 Apr 28. Epub 2021 Apr 28.

Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou 310058, China.

Background: Unprecedented rigorous public health measures were implemented during the COVID-19 epidemic, but it is still unclear how the intervention influenced hospital visits for different types of diseases. We aimed to evaluate the impact of the intervention on hospital visits in Yinzhou District, Ningbo, Zhejiang Province, China.

Methods: We conducted an interrupted time series analysis from January 1st, 2017 to September 6th, 2020 based on the Yinzhou Health Information System in Ningbo, Zhejiang province. The beginning of the intervention was on January 23rd, 2020, and thus, there were 160 weeks before the intervention and 32 weeks after the implementation of the intervention. Level changes between expected and observed hospital visits in the post-intervention period were estimated using quasi-Poisson regression models.

Results: Compared with the expected level, there was an estimated decrease of -22.60% (95% CI: -27.53%, -17.36%) in the observed total hospital visits following the intervention. Observed hospital visits for diseases of the respiratory system were found to be decreased dramatically (-62.25%, 95% CI: -65.62%, -58.60%). However, observed hospital visits for certain diseases were estimated to be increased, including diseases of the nervous system (+11.17%, 95% CI: +3.21%, +19.74%), diseases of pregnancy, childbirth and the puerperium (+27.01%, 95% CI:+17.89%, +36.85%), certain conditions originating in the perinatal period (+45.05%, 95% CI: +30.24%, +61.56%), and congenital malformations deformations and chromosomal abnormalities (+35.50%, 95% CI:+21.24%, +51.45%).

Conclusions: Our findings provided scientific evidence that cause-specific hospital visits evolved differently following the intervention during the COVID-19 epidemic.
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http://dx.doi.org/10.1093/intqhc/mzab078DOI Listing
April 2021

Bacterial hyperpolarization modulated by polyoxometalates for solutions of antibiotic resistance.

J Inorg Biochem 2021 Apr 15;220:111463. Epub 2021 Apr 15.

South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, China; Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materiasls and Devices, South China University of Technology, Guangzhou 510640, China. Electronic address:

Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaPWO] or [AgPWO]) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg influx by blocking Mg transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a 'dormant', slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111463DOI Listing
April 2021

Air pollution, surrounding green, road proximity and Parkinson's disease: A prospective cohort study.

Environ Res 2021 Apr 19;197:111170. Epub 2021 Apr 19.

Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China; Department of Epidemiology and Biostatistics, And Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China. Electronic address:

Background: Though growing evidence has linked air pollution to Parkinson's disease (PD), the results remain inconsistent. Less is known about the relevance of road proximity and surrounding green. We aimed to investigate the individual and joint associations of air pollution, road proximity and surrounding green with the incidence of PD in a prospective cohort study.

Methods: We used data from a prospective cohort of 47,516 participants recruited from July 2015 to January 2018 in Ningbo, China. Long-term exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PM) and ≤10 μm (PM) and nitrogen dioxide (NO) estimated by land-use regression models, road proximity and surrounding green assessed by Normalized Difference Vegetation Index (NDVI) were calculated based on the residential address for each participant. Cox proportional hazard models were used to analyze the individual and joint effects of air pollution, road proximity, and surrounding green on PD.

Results: In single-exposure models, PM, PM, NO and road proximity was associated with increased risk of PD (e.g. Hazard Ratio (HR) = 1.51, 95%CI:1.02, 2.24 per interquartile range (IQR) increase for PM) while surrounding green was associated with decreased risk of PD (e.g. HR = 0.80, 95%CI:0.65, 0.98 per IQR increase for NDVI in 300 m buffer). In two-exposure models, the associations of PM and surrounding green persisted while the associations of NO and road proximity attenuated towards unity.

Conclusions: We found that PM were associated with increased risk of incident PD while surrounding green was associated with decreased risk of PD. Future studies about PD etiology may benefit from including multiple environmental exposures to address potential joint associations.
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http://dx.doi.org/10.1016/j.envres.2021.111170DOI Listing
April 2021

Complete genome sequence analysis of the peanut pathogen Ralstonia solanacearum strain Rs-P.362200.

BMC Microbiol 2021 Apr 19;21(1):118. Epub 2021 Apr 19.

College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.

Background: Bacterial wilt caused by Ralstonia solanacearum species complex is an important soil-borne disease worldwide that affects more than 450 plant species, including peanut, leading to great yield and quality losses. However, there are no effective measures to control bacterial wilt. The reason is the lack of research on the pathogenic mechanism of bacterial wilt.

Results: Here, we report the complete genome of a toxic Ralstonia solanacearum species complex strain, Rs-P.362200, a peanut pathogen, with a total genome size of 5.86 Mb, encoding 5056 genes and the average G + C content of 67%. Among the coding genes, 75 type III effector proteins and 12 pseudogenes were predicted. Phylogenetic analysis of 41 strains including Rs-P.362200 shows that genetic distance mainly depended on geographic origins then phylotypes and host species, which associated with the complexity of the strain. The distribution and numbers of effectors and other virulence factors changed among different strains. Comparative genomic analysis showed that 29 families of 113 genes were unique to this strain compared with the other four pathogenic strains. Through the analysis of specific genes, two homologous genes (gene ID: 2_657 and 3_83), encoding virulence protein (such as RipP1) may be associated with the host range of the Rs-P.362200 strain. It was found that the bacteria contained 30 pathogenicity islands and 6 prophages containing 378 genes, 7 effectors and 363 genes, 8 effectors, respectively, which may be related to the mechanism of horizontal gene transfer and pathogenicity evaluation. Although the hosts of HA4-1 and Rs-P.362200 strains are the same, they have specific genes to their own genomes. The number of genomic islands and prophages in HA4-1 genome is more than that in Rs-P.36220, indicating a rapid change of the bacterial wilt pathogens.

Conclusion: The complete genome sequence analysis of peanut bacterial wilt pathogen enhanced the information of R. solanacearum genome. This research lays a theoretical foundation for future research on the interaction between Ralstonia solanacearum and peanut.
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http://dx.doi.org/10.1186/s12866-021-02157-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056632PMC
April 2021

Use of an electronic seizure diary in a randomized, controlled trial of natalizumab in adult participants with drug-resistant focal epilepsy.

Epilepsy Behav 2021 Apr 5;118:107925. Epub 2021 Apr 5.

Biogen, Cambridge, MA, USA. Electronic address:

Objective: To analyze electronic diary (e-diary) use in a phase 2, randomized, controlled clinical trial (OPUS; NCT03283371) of natalizumab in adult participants with drug-resistant focal epilepsy.

Methods: We developed an e-diary, which incorporated an episodic seizure diary and a daily diary reminder, for use as the primary source to record participants' daily seizure activity in the OPUS phase 2 clinical trial. Participants and/or their designated caregivers made e-diary entries by selecting seizure descriptions generated in the participants' and/or caregivers' own words at the time of screening. Seizures and seizure-free days were reported for the current day and for up to 5 and 4 retrospective days, respectively. A record of seizure symptoms entered within the prior 5-day period was displayed on accessing the diary. Changes were not permitted in the e-diary once a seizure record was saved unless a data change request was made. A paper backup diary was available.

Results: E-diary entries (N = 15,176) from the 6-week baseline period and subsequent 24-week placebo-controlled period were analyzed for 66 adults who were randomized and dosed in the OPUS trial. The overall e-diary compliance, defined as the total number of days with any entry out of the total number of days in the baseline and placebo-controlled periods for all participants combined, was 83.6%. Caregivers made 190 (1.3%) e-diary entries. Day-of-event e-diary entries totaled 11,248 (74.1%). At least one paper backup diary was used by 36 (54.5%) participants.

Significance: Our data highlight that good e-diary compliance can be achieved across participants in randomized clinical trials in adult focal epilepsy. In addition to identifying and addressing any barriers that may prevent a minority of participants from achieving good e-diary compliance, consideration of e-diary elements, such as recall period and reporting of seizure-free days, will facilitate the most accurate data capture in epilepsy clinical trials.
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http://dx.doi.org/10.1016/j.yebeh.2021.107925DOI Listing
April 2021

Online detection of class-imbalanced error-related potentials evoked by motor imagery.

J Neural Eng 2021 Apr 26;18(4). Epub 2021 Apr 26.

School of Information Engineering, Wuhan University of Technology, Wuhan 430070, People's Republic of China.

Error-related potentials (ErrPs) are spontaneous electroencephalogram signals related to the awareness of erroneous responses within brain domain. ErrPs-based correction mechanisms can be applied to motor imagery-brain-computer interface (MI-BCI) to prevent incorrect actions and ultimately improve the performance of the hybrid BCI. Many studies on ErrPs detection are mostly conducted under offline conditions with poor classification accuracy and the error rates of ErrPs are preset in advance, which is too ideal to apply in realistic applications. In order to solve these problems, a novel method based on adaptive autoregressive (AAR) model and common spatial pattern (CSP) is proposed for ErrPs feature extraction. In addition, an adaptive threshold classification method based spectral regression discriminant analysis (SRDA) is suggested for class-unbalanced ErrPs data to reduce the false positives and false negatives.As for ErrPs feature extraction, the AAR coefficients in the temporal domain and CSP in the spatial domain are fused. Given that the performance of different subjects' MI tasks is different but stable, and the samples of ErrPs are class-imbalanced, an adaptive threshold based SRDA is suggested for classification. Two datasets are used in this paper. The open public clinical neuroprosthetics and brain interaction (CNBI) dataset is used to validate the performance of the proposed feature extraction algorithm and the real-time data recorded in our self-designed system is used to validate the performance of the proposed classification algorithm under class-imbalanced situations. Different from the pseudo-random paradigm, the ErrPs signals collected in our experiments are all elicited by four-class of online MI-BCI tasks, and the sample distribution is more natural and suitable for practical tests.The experimental results on the CNBI dataset show that the average accuracy and false positive rate for ErrPs detection are 94.1% and 8.1%, which outperforms methods using features extracted from a single domain. What's more, although the ErrPs induction rate is affected by the performance of subjects' MI-BCI tasks, experimental results on data recorded in the self-designed system prove that the ErrPs classification algorithm based on an adaptive threshold is robust under different ErrPs data distributions. Compared with two other methods, the proposed algorithm has advantages in all three measures which are accuracy, F1-score and false positive rate. Finally, ErrPs detection results were used to prevent wrong actions in a MI-BCI experiment, and it leads to a reduction of the hybrid BCI error rate from 48.9% to 24.3% in online tests.Both the AAR-CSP fused feature extraction and the adaptive threshold based SRDA classification methods suggested in our work are efficient in improving the ErrPs detection accuracy and reducing the false positives. In addition, by introducing ErrPs to multi-class MI-BCIs, the MI decoding results can be corrected after ErrPs are detected to avoid executing wrong instructions, thereby improving the BCI accuracy and lays the foundation for using MI-BCIs in practical applications.
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http://dx.doi.org/10.1088/1741-2552/abf522DOI Listing
April 2021

Recent advances of small molecule focal adhesion kinase (FAK) inhibitors as promising anticancer therapeutics.

Curr Med Chem 2021 Mar 31. Epub 2021 Mar 31.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093. China.

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase involved in the process of cell proliferation, survival, migration, and invasion. It has become a promising therapeutic target for treatment of human metastatic cancers due to its overexpression and/or activation in multiple cancer types. Since FAK is emerging as a potential cancer target because of its overexpression at both the transcriptional and translational level in cancer, different types of FAK inhibitors with diversified scaffolds have been discovered in the past few years. In this review, the progress of recently discovered small molecule FAK inhibitors was summarized. Major efforts have been focused on the rational design and synthesis of small molecule FAK inhibitors, and their structure-activity relationship (SAR) analysis were also discussed. Among them, while type I inhibitors remain as the major focuses, type II inhibitors and novel allosteric FAK inhibitors (type III inhibitors) have been developed to improve both potency and selectivity. Meanwhile, novel strategies, such as targeting FAK using inhibitors of protein-protein interactions were also discovered. Lastly, some insights and perspectives on the future development of FAK inhibitors as anticancer therapeutics have been provided.
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http://dx.doi.org/10.2174/0929867328666210331143827DOI Listing
March 2021

Polymer-templated supramolecular co-assemblies of proteins and metal oxide clusters as versatile platform for chemo-enzymatic catalysis.

J Colloid Interface Sci 2021 Jul 19;594:874-881. Epub 2021 Mar 19.

South China Advanced Institute for Soft Matter Science and Technology & State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, PR China. Electronic address:

The hybridization of enzymes and inorganics in controlled manner is challenging, however, critical for the development of chemo-enzymatic cascade catalyst with high efficiency and selectivity. Here, proteins and metal oxide clusters can be facilely co-assembled on the surface of colloid of poly(4-vinylpyridine) (P4VP) via hydrogen bonding, due to their enriched surface hydrogen bonding donors. The co-assembly method can be generally applied for preparing chemo-enzymatic catalyst within the selected database of various proteins and metal oxide clusters while the assembly units retain their structures and activities. Typically, a 2.5 nm metal oxide cluster {MoFe}, with peroxidase-like activity, are complexed with glucose oxidase (GOX) on P4VP for the catalysis against the oxidization of o-dianisidine (ODA) with the existence of glucose. Due to the synergistic effects of chemical and enzymatic catalysis, the co-assemblies show even higher ODA oxidation activity compared to GOX/catalase bi-enzymatic system, confirming the effectiveness of the co-assembly protocol for cascade catalysis and enabling its applications in rapid glucose detection and biomass conversion.
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http://dx.doi.org/10.1016/j.jcis.2021.03.090DOI Listing
July 2021

In Situ Ultrafast and Patterned Growth of Transition Metal Dichalcogenides from Inkjet-Printed Aqueous Precursors.

Adv Mater 2021 Apr 18;33(16):e2100260. Epub 2021 Mar 18.

Department of Electronic Engineering and Materials Science and Technology Research Center, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, 999077, P. R. China.

Chemical vapor deposition (CVD) has been widely used to synthesize high-quality 2D transition-metal dichalcogenides (TMDCs) from different precursors. At present, quantitative control of the precursor with high precision and good repeatability is still challenging. Moreover, the process to synthesize TMDCs with designed patterns is complicated. Here, by using an industrial inkjet-printer, an in situ aqueous precursor with robust usage control at the picogram (10 g) level is achieved, and by precisely tuning the inkjet-printing parameters, followed by a rapid heating process, large-area patterned TMDC films with centimeter size and good thickness controllability, as well as heterostructures of the TMDCs, are achieved facilely, and high-quality single-domain monolayer TMDCs with millimeter-size can be easily synthesized within 30 s (corresponding to a growth rate up to 36.4 µm s ). The resulting monolayer MoS and MoSe exhibits excellent electronic properties with carrier mobility up to 21 and 54 cm V s , respectively. The study paves a simple and robust way for the in situ ultrafast and patterned growth of high-quality TMDCs and heterostructures with promising industrialization prospects. Moreover, this ultrafast and green method can be easily used for synthesis of other 2D materials with slight modification.
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http://dx.doi.org/10.1002/adma.202100260DOI Listing
April 2021

PD-1 restrains IL-17A production from γδ T cells to modulate acute radiation-induced lung injury.

Transl Lung Cancer Res 2021 Feb;10(2):685-698

Central Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shen Zhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.

Background: Combining radiotherapy (RT) with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has been shown to enhance anti-tumor effects in the treatment of non-small cell lung carcinoma (NSCLC). Pulmonary toxicity is a major adverse effect of thoracic RT in NSCLC patients, whether it is administered alone or in combination with PD-1/PD-L1 inhibitors. This study aimed to evaluate the potential pulmonary toxicity of RT combined with concurrent PD-1 inhibitor and to clarify the underlying mechanisms.

Methods: Radiation-induced lung injury (RILI) was induced in C57BL/6 mice by given 24 Gy in three fractions on consecutive days, with or without concurrent injection of anti-PD-1 antibody. On days 3, 7, 14, and 28 after the first exposure to irradiation, lung tissue and peripheral blood samples were collected from the mice. Histological injury was analyzed, and inflammatory cell infiltration and interleukin (IL)-17A production in the lung tissues were quantified.

Results: Mice that received irradiation with concurrent administration of anti-PD-1 antibody had the highest histological score for RILI. In the murine lung tissues, the levels of PD-1 and IL-17A expression were increased in γδ T cells but not in the other CD3 T cells after irradiation. Concurrent blockade of PD-1 enhanced IL-17A production from γδ T cells in the lung tissues after irradiation. In the mice with acute RILI, concurrent administration of anti-PD-1 antibody exaggerated pulmonary inflammation, with significantly increased levels of neutrophilic infiltration and IL-17A detected in both the lung and blood.

Conclusions: PD-1 could restrain IL-17A production from γδ T cells to modulate acute RILI. The concurrent administration of anti-PD-1 antibody aggravates the severity of acute RILI. More attention should be paid to pulmonary toxicity in patients undergoing thoracic RT with concurrent anti-PD-1 immunotherapy.
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http://dx.doi.org/10.21037/tlcr-20-838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947382PMC
February 2021

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predict Mortality in Patients with Diabetic Foot Ulcers Undergoing Amputations.

Diabetes Metab Syndr Obes 2021 24;14:821-829. Epub 2021 Feb 24.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Purpose: Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations.

Patients And Methods: A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan-Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort.

Results: All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively (=0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% (<0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045-1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351-3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014-3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177-3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001-1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081-1.232, p<0.001) were independent predictors of mortality following amputation.

Conclusion: Postoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.
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http://dx.doi.org/10.2147/DMSO.S284583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917326PMC
February 2021

Molecular design of energetic tetrazine-triazole derivatives.

J Mol Model 2021 Feb 28;27(3):98. Epub 2021 Feb 28.

School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Nitrogen-rich compounds are promising candidates for preparing high energetic density materials (HEDMs) and show the potential in the application of propellants, explosives, and pyrotechnics. Two kinds of typical nitrogen-rich compounds, such as tetrazine and triazole, have attracted the attentions in recent years owing to their high densities, good thermal stabilities, and excellent energetic performances. In this work, four series of innovative energetic compounds based on the conjugates of tetrazine and triazole bearing various substituents (-NH, -NO, and -NHNO) were designed. The optimized structures, crystal densities, heats of formation (HOFs) in gas phase and in condensed phase, detonation properties, bond dissociation energies (BDEs), and impact sensitivity (h) of these compounds were studied systematically via density functional theory (DFT) method. The detonation velocities of four series of compounds are in the range between 7.03 and 8.59 km s and their detonation pressures are in the range between 20.6 and 33.1 GPa. Results indicated that the linkage of -N=N- bond contributed significantly to HOFs and energy density of the energetic molecules, and 1,2,3-triazole showed better performances than 1,2,4-triazole slightly. As for the same series compounds with different substituents, the compounds with -NHNO possessed the highest HOFs (such as A6, B6, C6, D6). In terms of the energetic properties (D and P), four compounds (A7, B7, C7, and D7) exhibited the comparable performance with the widely used hexa-hydro-1,3,5-trinitro-1,3,5-triazine (RDX) and in the meanwhile displayed superior thermal stability and sensitivity to RDX, which indicated their potential application in the insensitive energetic materials.
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http://dx.doi.org/10.1007/s00894-021-04714-3DOI Listing
February 2021

Novel impedimetric sensing strategy for detecting ochratoxin A based on NH-MIL-101(Fe) metal-organic framework doped with cobalt phthalocyanine nanoparticles.

Food Chem 2021 Jul 18;351:129248. Epub 2021 Feb 18.

College of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450001, PR China. Electronic address:

Iron-based metal-organic framework, NH-MIL-101(Fe), was doped with different dosages of cobalt phthalocyanine nanoparticles (CoPc) to synthesize a series of NH-MIL-101(Fe)@CoPc nanocomposites. The NH-MIL-101(Fe)@CoPc nanocomposites were then employed to construct novel impedimetric aptasensors for the detection of ochratoxin A (OTA). Combining the intrinsic advantages of NH-MIL-101(Fe) (highly porous structure and excellently electrochemical activity) and CoPc (good physiochemical stability and strong bioaffinity), the NH-MIL-101(Fe)@CoPc nanocomposites show promising properties, which are beneficial for immobilizing OTA-targeted aptamer strands. Amongst, the developed impedimetric aptasensor based on NH-MIL-101(Fe)@CoPc, prepared using the mass ratio of NH-MIL-101(Fe):CoPc of 6:1, exhibits the best amplified electrochemical signal and highest sensitivity for detecting OTA. The detection limitation is 0.063 fg·mL within the OTA concentration of 0.0001-100 pg·mL, accompanying with high selectivity, good reproducibility and stability, acceptable regenerability, and wide applicability in diverse real samples. Consequently, the proposed sensing strategy can be applied for detecting OTA to cope with food safety.
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http://dx.doi.org/10.1016/j.foodchem.2021.129248DOI Listing
July 2021

GhMYB4 downregulates lignin biosynthesis and enhances cotton resistance to Verticillium dahliae.

Plant Cell Rep 2021 Apr 27;40(4):735-751. Epub 2021 Feb 27.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Key Message: GhMYB4 acts as a negative regulator in lignin biosynthesis, which results in alteration of cell wall integrity and activation of cotton defense response. Verticillium wilt of cotton (Gossypium hirsutum) caused by the soil-borne fungus Verticillium dahliae (V. dahliae) represents one of the most important constraints of cotton production worldwide. Mining of the genes involved in disease resistance and illuminating the molecular mechanisms that underlie this resistance is of great importance in cotton breeding programs. Defense-induced lignification in plants is necessary for innate immunity, and there are reports of a correlation between increased lignification and disease resistance. In this study, we present an example in cotton whereby plants with reduced lignin content also exhibit enhanced disease resistance. We identified a negative regulator of lignin synthesis, in cotton encoded in GhMYB4. Overexpression of GhMYB4 in cotton and Arabidopsis enhanced resistance to V. dahliae  with reduced lignin deposition. Moreover, GhMYB4 could bind the promoters of several genes involved in lignin synthesis, such as GhC4H-1, GhC4H-2, Gh4CL-4, and GhCAD-3, and impair their expression. The reduction of lignin content in GhMYB4-overexpressing cotton led to alterations of cell wall integrity (CWI) and released more oligogalacturonides (OGs) which may act as damage-associated molecular patterns (DAMPs) to stimulate plant defense responses. In support of this hypothesis, exogenous application with polygalacturonic acid (PGA) in cotton activated biosynthesis of jasmonic acid (JA) and JA-mediated defense against V. dahliae, similar to that described for cotton plants overexpressing GhMYB4. This study provides a new candidate gene for cotton disease-resistant breeding and an increased understanding of the relationship between lignin synthesis, OG release, and plant immunity.
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http://dx.doi.org/10.1007/s00299-021-02672-xDOI Listing
April 2021

Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results of a phase I, open-label crossover study in healthy volunteers.

Ther Adv Neurol Disord 2021 22;14:1756286420975227. Epub 2021 Jan 22.

Biogen, 225 Binney St., Cambridge, MA 02142, USA.

Background: Peginterferon beta-1a administered every 2 weeks subcutaneous (SC) injection is approved to treat adult patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). However, associated injection site reactions (ISRs) can lead to treatment discontinuation. Prior studies with interferon beta-1a reported a lower frequency of ISRs with intramuscular (IM) administration than with SC administration. IM administration of peginterferon beta-1a may therefore represent a useful alternative treatment option.

Methods: A phase I, open-label, two-period crossover study randomized healthy volunteers to receive a single dose of peginterferon beta-1a 125 mcg administered IM followed by a single 125 mcg dose administered SC after a 28-day washout or vice versa. Blood samples were collected up to 504 h post dose to determine pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The primary endpoint was assessment of bioequivalence based on maximum serum concentration (C) and area under the curve from time zero extrapolated to infinity (AUC). Other PK parameters, as well as PD (serum neopterin) and safety profiles, were also evaluated.

Results: The study enrolled 136 participants. Bioequivalence of IM and SC peginterferon beta-1a was established for both C ([least squares (LS)] mean IM/SC ratio: 1.083 [90% confidence interval (CI), 0.975-1.203]) and AUC (LS mean IM/SC ratio: 1.089 [90% CI, 1.020-1.162]). Other PK and PD parameters were similar between administration routes, although moderate to high inter-subject variability was observed for IM and SC. Safety profiles were generally balanced between IM and SC administration. ISRs occurred at a lower frequency with IM [14.4% (95% CI, 8.89-21.56%)] than with SC [32.1% (95% CI, 24.29-40.70%)] administration ( = 0.0005).

Conclusions: These results demonstrate bioequivalence between peginterferon beta-1a IM and SC and support the consideration of IM injection of peginterferon beta-1a as a viable treatment option in patients with RRMS and RMS.
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http://dx.doi.org/10.1177/1756286420975227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883310PMC
January 2021

Metformin attenuates post-epidural fibrosis by inhibiting the TGF-β1/Smad3 and HMGB1/TLR4 signaling pathways.

J Cell Mol Med 2021 Apr 21;25(7):3272-3283. Epub 2021 Feb 21.

NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, China.

Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-β1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy.
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http://dx.doi.org/10.1111/jcmm.16398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034438PMC
April 2021

Periodic mesoporous organosilica-coated magnetite nanoparticles combined with lipiodol for transcatheter arterial chemoembolization to inhibit the progression of liver cancer.

J Colloid Interface Sci 2021 Jun 10;591:211-220. Epub 2021 Feb 10.

Department of Interventional Therapy, Department of Radiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu, PR China. Electronic address:

Transcatheter arterial chemoembolization (TACE) is standard locoregional therapy for hepatocellular carcinoma (HCC) that involves the injection of chemotherapeutic drugs with embolic agents into tumor tissues through intra-arterial transcatheter infusion. TACE technology using lipiodol emulsion has been most widely used in the treatment of human HCC. However, lipiodol emulsions with anticancer drugs do not stably maintain high drug concentrations at tumor sites. Herein, we developed a dual-modality imaging nanoplatform for the TACE treatment of liver cancer by integrating periodic mesoporous organosilica (PMO) with magnetite (FeO) nanoparticles and Cy5.5 molecules (denoted as FeO@PMO-Cy5.5). FeO@PMO-Cy5.5 showed an excellent doxorubicin (Dox)-loading capacity, sensitive drug release behavior under acidic conditions, and good biocompatibility. Moreover, Cy5.5-mediated optical imaging showed that Dox-loaded FeO@PMO-Cy5.5 (FeO@PMO-Cy5.5-Dox) could enter liver cancer cells and effectively inhibit their growth. In addition, FeO@PMO-Cy5.5-Dox was used in combination with transarterial embolization for the treatment of in situ VX2 liver tumors in rabbits. Magnetic resonance imaging (MRI) evaluation showed that FeO@PMO-Cy5.5-Dox perfused through arteries was deposited into liver tumors, and FeO@PMO-Cy5.5-Dox combined with lipiodol to control liver tumors yielded the optimal therapeutic effect. In addition, histological analysis showed that compared with both lipiodol embolization and traditional lipiodol combined with Dox chemoembolization, FeO@PMO-Cy5.5-Dox combined with lipiodol chemoembolization induced more complete tumor tissue necrosis. In summary, these results indicate that the FeO@PMO-Cy5.5-Dox platform has the potential to become an advanced tool for the transarterial treatment of unresectable liver cancer.
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http://dx.doi.org/10.1016/j.jcis.2021.02.022DOI Listing
June 2021

A far-red emissive two-photon fluorescent probe for quantification of uracil in genomic DNA.

Chem Commun (Camb) 2021 Mar;57(22):2784-2787

The Institute of Advanced Studies, College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, Hubei 430072, China.

We report a new method for dU detection in genomic DNA combined with UNG excision and fluorescent probe labeling. UNG can remove uracil bases to introduce abasic sites, which can react with NRNO to produce intense fluorescence because of the inhibition of the PET effect. It can also cause the polymerase extension to stop to provide details of dU site information.
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http://dx.doi.org/10.1039/d1cc00016kDOI Listing
March 2021

Impact of temperature and relative humidity on the transmission of COVID-19: a modelling study in China and the United States.

BMJ Open 2021 02 17;11(2):e043863. Epub 2021 Feb 17.

Department of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, New York, USA.

Objectives: We aim to assess the impact of temperature and relative humidity on the transmission of COVID-19 across communities after accounting for community-level factors such as demographics, socioeconomic status and human mobility status.

Design: A retrospective cross-sectional regression analysis via the Fama-MacBeth procedure is adopted.

Setting: We use the data for COVID-19 daily symptom-onset cases for 100 Chinese cities and COVID-19 daily confirmed cases for 1005 US counties.

Participants: A total of 69 498 cases in China and 740 843 cases in the USA are used for calculating the effective reproductive numbers.

Primary Outcome Measures: Regression analysis of the impact of temperature and relative humidity on the effective reproductive number ( value).

Results: Statistically significant negative correlations are found between temperature/relative humidity and the effective reproductive number ( value) in both China and the USA.

Conclusions: Higher temperature and higher relative humidity potentially suppress the transmission of COVID-19. Specifically, an increase in temperature by 1°C is associated with a reduction in the value of COVID-19 by 0.026 (95% CI (-0.0395 to -0.0125)) in China and by 0.020 (95% CI (-0.0311 to -0.0096)) in the USA; an increase in relative humidity by 1% is associated with a reduction in the value by 0.0076 (95% CI (-0.0108 to -0.0045)) in China and by 0.0080 (95% CI (-0.0150 to -0.0010)) in the USA. Therefore, the potential impact of temperature/relative humidity on the effective reproductive number alone is not strong enough to stop the pandemic.
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http://dx.doi.org/10.1136/bmjopen-2020-043863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893211PMC
February 2021

Retroperitoneal teratoma resection assisted by 3-dimensional visualization and virtual reality: A case report.

World J Clin Cases 2021 Feb;9(4):935-942

Department of Hepatobiliary Surgery, Xiang'an Hospital, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China.

Background: Primary retroperitoneal tumor is a rare type of tumor with insidious onset, large tumor size at the time of diagnosis, and often extensive involvement of surrounding tissues and blood vessels in the retroperitoneum. Surgery for primary retroperitoneal tumors is technically challenging. Preoperative imaging evaluation is critical for the selection of the optimal surgical approach and can influence complete resection and recurrence rates. Three-dimensional model reconstruction combined with virtual reality is useful for preoperative assessment.

Case Summary: A 17-year-old female patient was admitted for abdominal pain lasting for half a year that had been worsening for half a month. Abdominopelvic enhanced helical computed tomography revealed a retroperitoneal space-occupying lesion about 11.3 cm × 9.1 cm in size, with well-defined borders in the upper left quadrant of the abdomen. The lesion compressed the left renal artery and vein resulting in vascular displacement and deformation. A multidisciplinary team decided on the optimal treatment approach. Preoperative three-dimensional visualization and virtual reality technology were used to assess and simulate the surgical procedure. Then, retroperitoneal tumor resection along with renal artery reconstruction was decided as the treatment. Complete resection of the retroperitoneal tumor was performed. Stable blood flow was established after renal artery reconstruction. The tumor was diagnosed as mature cystic teratoma (retroperitoneal tumor) by postoperative pathologic analysis. The patient, who recovered well, was discharged after 2 wk and maintains regular follow-ups.

Conclusion: A combination of three-dimensional reconstruction and virtual reality technology before surgery improves the rate of complete resection of retroperitoneal teratoma.
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http://dx.doi.org/10.12998/wjcc.v9.i4.935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852646PMC
February 2021

Development of an Immune-Related Gene Signature for Prognosis in Melanoma.

Front Oncol 2020 21;10:602555. Epub 2021 Jan 21.

Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, China.

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma.
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http://dx.doi.org/10.3389/fonc.2020.602555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874014PMC
January 2021

Affective Temperament Traits Measured by TEMPS-A and Their Associations with Cognitive Functions among Offspring of Parents with Bipolar Disorder with and without Subthreshold Symptoms.

J Affect Disord 2021 03 2;283:377-383. Epub 2021 Feb 2.

Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, 510370, China; Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. Electronic address:

Background: To our knowledge, there have been no studies that have examined affective temperament traits in offspring of parents with bipolar disorder (BD). The aim of this study was to identify affective temperamental characteristics and their relationships with cognitive functions in BD offspring.

Methods: A group of BD offspring were enrolled in this study. Subthreshold symptoms were used to categorize participants as either symptomatic offspring (SO) (n=60) or asymptomatic offspring (AO) (n=52). Healthy controls (HCs; n=48) were also enrolled for comparison. We used the Chinese Short Version of Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire (TEMPS-A) to measure temperament traits, and MATRICS Consensus Cognitive Battery (MCCB) to measure cognitive functions.

Results: We observed higher cyclothymic, irritable, depressive and anxious temperament scores in SO than AO when compared to HCs. In BD offspring (SO and AO), cyclothymic individuals performed better in processing speed and verbal learning than depressive individuals and better in attention/vigilance than irritable and anxious individuals; hyperthymic individuals performed better in processing speed than depressive individuals. We also observed that a higher cyclothymic score was associated with better verbal learning and verbal fluency, a higher hyperthymic score was associated with better processing speed and verbal learning; while a higher depressive score was associated with worse processing speed, verbal learning and verbal fluency and a higher irritable score was associated with worse attention/vigilance.

Conclusions: The relationships between cognitive functions and measures of temperament suggest that these features may share neurobiological substrates and appear to be heritable.
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http://dx.doi.org/10.1016/j.jad.2021.01.061DOI Listing
March 2021

Preparation and evaluation of ion-exchange porous polyvinyl alcohol microspheres as a potential drug delivery embolization system.

Mater Sci Eng C Mater Biol Appl 2021 Feb 15;121:111889. Epub 2021 Jan 15.

Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address:

The present study aimed to develop a new drug delivery system with efficient drug loading and sustained drug release for potential application in transarterial chemoembolization (TACE). The porous polyvinyl alcohol microspheres (PPVA MS) were prepared by a combination of inverse emulsification and thermal-induced phase separation (TIPS) method, this was followed by the grafting polymerization of sodium 4-styrene sulfonate (SSS) onto the PPVA MS to obtain the grafted PPVA-g-PSSS MS. The prepared PPVA MS showed a well-defined spherical shape with 'honeycomb-like' porous structure, which could be readily tailored by adjusting the quenching temperature. In vitro biocompatibility analysis indicated the non-cytotoxic and hemocompatible nature of PPVA MS. The porous structure and presence of ionically charged groups in the PPVA-g-PSSS MS favoured the loading of cationic doxorubicin (DOX) onto the MS through ionic-interactions and demonstrated a sustained drug release pattern. Moreover, the cytotoxicity of DOX-loaded PPVA-g-PSSS (DOX@PPVA-g-PSSS) MS against HepG2 cells and the intracellular uptake of DOX demonstrated the potent in vitro antitumor activity. Furthermore, the central auricular artery embolization in rabbits showed that both the PPVA-g-PSSS and DOX@PPVA-g-PSSS MS could occlude the auricular arteries and induced superior embolization effects, such as progressive ear appearance changes, irreversible parenchymal damage and fibrosis, and ultrastructural alternations in endothelial cells. Besides, the DOX fluorescence was distributed around the embolized arteries, without decreasing its intensity when prolonged embolization up to 15 days. These findings suggest that the newly developed DOX@PPVA-g-PSSS MS could be employed as a promising drug-loaded embolic agent for the treatment of hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.msec.2021.111889DOI Listing
February 2021

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study.

Transl Psychiatry 2021 Feb 5;11(1):111. Epub 2021 Feb 5.

Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China.

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049-0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.
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http://dx.doi.org/10.1038/s41398-021-01222-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864939PMC
February 2021

Early versus late tracheotomy in ICU patients: A meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Jan;100(3):e24329

Intensive Care Unit, Affiliated Jinhua hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.

Background: This study aimed to quantitatively analyze the available randomized controlled trials (RCTs) and investigate whether early tracheotomy can improve clinical endpoints compared with late tracheotomy in critically ill patients undergoing mechanical ventilation.

Methods: The electronic databases of PubMed, Embase, and the Cochrane library were systematically searched in August 2019. The investigated outcomes were calculated using relative risks (RRs) and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) through the random-effects model for categories and continuous data, respectively.

Results: The electronic searches yielded 2289 records, including 15 RCTs comprising a total of 3003 patients and found to be relevant for the final quantitative analysis. The summary RRs that indicated early versus late tracheotomy were not associated with the risk of short-term mortality (RR: 0.87; 95% CI: 0.74-1.03; P = .114) and ventilator-associated pneumonia (RR: 0.90; 95% CI: 0.78-1.04; P = .156). Moreover, early tracheotomy was associated with shorter intensive care unit (ICU) stay (SMD: -1.81; 95% CI: -2.64 to -0.99; P < .001) and mechanical ventilation duration (SMD: -1.17; 95% CI: -2.10 to -0.24; P = .014). Finally, no significant difference was observed between early and late tracheotomy for hospital stay (SMD: -0.42; 95% CI: -1.36-0.52; P = .377).

Conclusions: The present meta-analysis suggests that early tracheotomy can reduce the length of ICU stay and mechanical ventilation duration, but the timing of the tracheotomy was not associated with the short-term clinical endpoints in critically ill patients undergoing mechanical ventilation.
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http://dx.doi.org/10.1097/MD.0000000000024329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837817PMC
January 2021

Pursuing sources of heterogeneity in modeling clustered population.

Biometrics 2021 Feb 2. Epub 2021 Feb 2.

Department of Statistics, University of Connecticut, Storrs, Connecticut.

Researchers often have to deal with heterogeneous population with mixed regression relationships, increasingly so in the era of data explosion. In such problems, when there are many candidate predictors, it is not only of interest to identify the predictors that are associated with the outcome, but also to distinguish the true sources of heterogeneity, that is, to identify the predictors that have different effects among the clusters and thus are the true contributors to the formation of the clusters. We clarify the concepts of the source of heterogeneity that account for potential scale differences of the clusters and propose a regularized finite mixture effects regression to achieve heterogeneity pursuit and feature selection simultaneously. We develop an efficient algorithm and show that our approach can achieve both estimation and selection consistency. Simulation studies further demonstrate the effectiveness of our method under various practical scenarios. Three applications are presented, namely, an imaging genetics study for linking genetic factors and brain neuroimaging traits in Alzheimer's disease, a public health study for exploring the association between suicide risk among adolescents and their school district characteristics, and a sport analytics study for understanding how the salary levels of baseball players are associated with their performance and contractual status.
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http://dx.doi.org/10.1111/biom.13434DOI Listing
February 2021