Publications by authors named "Deng Chen"

147 Publications

Synthetic Biology Toolkits and Metabolic Engineering Applied in for Biomanufacturing.

ACS Synth Biol 2021 Dec 2. Epub 2021 Dec 2.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China.

is an important workhorse in industrial white biotechnology. It has been widely applied in the producing processes of amino acids, fuels, and diverse value-added chemicals. With the continuous disclosure of genetic regulation mechanisms, various strategies and technologies of synthetic biology were used to design and construct cells for biomanufacturing and bioremediation. This study mainly aimed to summarize the design and construction strategies of -engineered strains, which were based on genomic modification, synthetic biological device-assisted metabolic flux optimization, and directed evolution-based engineering. Then, taking two important bioproducts (-acetylglucosamine and hyaluronic acid) as examples, the applications of cell factories were introduced. Finally, we discussed the current challenges and future development trends of -engineered strain construction.
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http://dx.doi.org/10.1021/acssynbio.1c00355DOI Listing
December 2021

Effectiveness of Postoperative or Preoperative Radiotherapy on Prognosis in Patients with Stage II Resectable Non-Small Cell Lung Cancer: A Retrospective Study Based on the SEER Database.

Medicina (Kaunas) 2021 Nov 4;57(11). Epub 2021 Nov 4.

School of Public Health, Fudan University, Shanghai 200433, China.

: The research on the therapeutic effect of preoperative radiotherapy (PRRT) for patients with early non-small cell lung cancer (NSCLC) is still insufficient, and the impact of postoperative radiotherapy (PORT) on the prognosis of patients with early NSCLC remains controversial. We conducted this study to investigate the effect of PORT and PRRT on prognosis for these patients. : In total, 3640 patients with stage II NSCLC who underwent a lobectomy or pneumonectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression was adopted to identify the independent influence of PORT or PRRT on patients' prognosis. Subgroup analysis of survival was performed in patients with different combinations of key clinical features. We also used Kaplan-Meier analysis and competitive risk analysis to explore to which extent PORT or PRRT impacted the overall survival and cumulative mortality. : PORT was an independent risk factor of NSCLC-specific death among patients with N0 stage (HR, 1.648; 95% CI, 1.309-2.075, < 0.001) and in N1 stage with <3 positive lymph nodes (HR, 2.698; 95% CI, 1.910-3.812, < 0.001) in multivariate analysis. Findings from subgroup analysis for the risk of NSCLC-specific death, competitive risk analysis of NSCLC-specific cumulative mortality, and overall survival analysis also demonstrated PORT was detrimental to patients in these two subgroups above ( < 0.05). However, in patients with N1 stage with ≥3 positive lymph nodes, PORT may help prolong median survival. PRRT was an independent risk factor for NSCLC-specific death in multivariate analysis of patients with N0 stage (HR, 1.790; 95% CI, 1.201-2.668, = 0.004), and significantly decreased overall survival in these patients ( < 0.001). : PORT is associated with worse survival outcome and better cumulative mortality of stage II patients of NSCLC with N0 disease or N1 disease (<3 nodes), while PRRT is associated with reduced prognosis in patients with N0 stage. On the other hand, PORT may help to improve the prognosis of patients with N1 stage who have three or more lymph node metastases. Hence, PORT and PRRT should not be recommended for patients with N0 stage. However, in patients with "high volume" N1 stage, PORT might improve oncological outcomes.
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http://dx.doi.org/10.3390/medicina57111202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624228PMC
November 2021

Thoracic Spine Fractures with Blunt Aortic Injury: Incidence, Risk Factors, and Characteristics.

J Clin Med 2021 Nov 9;10(22). Epub 2021 Nov 9.

Division of Trauma & Surgical Critical Care, Department of Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Background: The coexistence of thoracic fractures and blunt aortic injury (BAI) is potentially catastrophic and easy to be missed in acute trauma settings. Data regarding patients with thoracic fractures complicated with BAI are limited.

Methods: The authors conducted a prospective, observational, single-center study including patients with thoracic burst fractures. A multivariate logistic regression model was developed to determine the risk factors of aortic injury.

Results: In total, 124 patients with burst fractures of the thoracic spine were included. The incidence of BAI was 11.3% (14/124) in patients with thoracic burst fractures. Among these patients, 11 patients with BAI were missed diagnoses. The main risk factors of BAI were as follows: Injury severity score (OR 1.184; 95% CI, 1.072-1.308; = 0.001), mechanism of injury, such as crush (OR 10.474; 95% CI, 1.905-57.579; = 0.007), flail chest (OR = 4.917; 95% CI, 1.122-21.545; = 0.035), and neurological deficit (OR = 8.299; 95% CI, 0.999-68.933; = 0.05).

Conclusions: BAI (incidence 11.3%) is common in patients with burst fractures of the thoracic spine and is an easily missed diagnosis. We must maintain a high suspicion of injury for BAI when patients with thoracic burst fractures present with these high-risk factors.
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http://dx.doi.org/10.3390/jcm10225220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623488PMC
November 2021

Reliability, Validity, and Responsiveness of the Chinese Learning Accomplishment Profile (C-LAP).

Children (Basel) 2021 Oct 28;8(11). Epub 2021 Oct 28.

Institute of Clinical Epidemiology, Key Laboratory of Public Health Safety, Ministry of Education, Key Lab of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai 200433, China.

Objectives: To evaluate the reliability, validity, and responsiveness of the Chinese Learning Accomplishment Profile in China.

Methods: 12,098 participants aged from 0 to 36 months from 30 provinces (mostly from Shanghai) in China were enrolled between 2013 and 2020. The reliability was reflected by Pearson correlation coefficients, Cronbach's alpha coefficients and standard errors; the validity was shown by the coefficients between the dimensions, and we also evaluated the responsiveness as a supplement to the validity.

Results: Reliability: in six domains among each subgroup, Pearson correlation coefficients between developmental age and chronological age ranged from 0.89 to 0.98, Cronbach's alpha coefficients from 0.71 to 0.99, and standard errors from 0.15 to 2.76.

Validity: after controlling for chronological age, the correlation coefficients between the dimensions were between 0.18 and 0.78, and most of them were below 0.70. Responsiveness: developmental age of all domains obtained via the Chinese Learning Accomplishment Profile system changed significantly ( < 0.001) with time (gap of 1-3 months), and the standardized response mean ranged from 0.66 to 2.45.

Conclusions: The Chinese Learning Accomplishment Profile is suitable for assessing children's development in Shanghai, but still needs confirmation when used in other provinces in China due to the great differences between regions in China.
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http://dx.doi.org/10.3390/children8110974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622609PMC
October 2021

Modulating CRISPR/Cas9 genome-editing activity by small molecules.

Drug Discov Today 2021 Nov 22. Epub 2021 Nov 22.

Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen 9713 AV, the Netherlands. Electronic address:

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated genome engineering has become a standard procedure for creating genetic and epigenetic changes of DNA molecules in basic biology, biotechnology, and medicine. However, its versatile applications have been hampered by its overall low precise gene modification efficiency and uncontrollable prolonged Cas9 activity. Therefore, overcoming these problems could broaden the therapeutic use of CRISPR/Cas9-based technologies. Here, we review small molecules with the clinical potential to precisely modulate CRISPR/Cas9-mediated genome-editing activity and discuss their mechanisms of action. Based on these data, we suggest that direct-acting small molecules for Cas9 are more suitable for precisely regulating Cas9 activity. These findings provide useful information for the identification of novel small-molecule enhancers and inhibitors of Cas9 and Cas9-associated endonucleases.
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http://dx.doi.org/10.1016/j.drudis.2021.11.018DOI Listing
November 2021

Abnormal corpus callosum induced by overt hepatic encephalopathy impairs interhemispheric functional coordination in cirrhosis patients.

Ann Transl Med 2021 Oct;9(20):1579

Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Although overt hepatic encephalopathy (OHE) patients were shown to have bilaterally symmetrical structural and functional abnormalities in the whole brain, few studies have focused on the bilateral cerebral hemisphere commissural fibers and measured functional coordination between bilateral hemispheres. This study aimed to investigate the structural changes of the corpus callosum (CC) and interhemispheric functional coordination in patients with OHE and to test the hypothesis that abnormal CC induced by OHE impairs interhemispheric functional coordination in cirrhosis patients.

Methods: The microstructural integrity and the volumes of each subregion of the CC were analyzed by diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging. Voxel-mirrored homotopic connectivity (VMHC) was derived from resting-state functional magnetic resonance imaging (MRI).

Results: Compared with the healthy controls (HCs) and patients without hepatic encephalopathy (noHE), the OHE group showed decreased volumes in all subregions of the CC. In OHE patients, the decreased fractional anisotropy (FA) of CC-5 correlated with decreased VMHC in the middle occipital gyrus (MOG) and precuneus. The value of FA in CC-5 and the volumes of CC-3, CC-4, and CC-5 showed correlations with neuropsychological performance in patients with OHE.

Conclusions: These findings suggest that impairment of interhemispheric white matter pathways may disturb the functional connectivity associated with coordination and neurocognitive performance.
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http://dx.doi.org/10.21037/atm-21-5109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576733PMC
October 2021

Ectomycorrhizal Fungal Strains Facilitate Cd Enrichment in a Woody Hyperaccumulator under Co-Existing Stress of Cadmium and Salt.

Int J Mol Sci 2021 Oct 28;22(21). Epub 2021 Oct 28.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.

Cadmium (Cd) pollution occurring in salt-affected soils has become an increasing environmental concern in the world. Fast-growing poplars have been widely utilized for phytoremediation of soil contaminating heavy metals (HMs). However, the woody Cd-hyperaccumulator, × , is relatively salt-sensitive and therefore cannot be directly used to remediate HMs from salt-affected soils. The aim of the present study was to testify whether colonization of × with ectomycorrhizal (EM) fungi, a strategy known to enhance salt tolerance, provides an opportunity for affordable remediation of Cd-polluted saline soils. Ectomycorrhization with strains facilitated Cd enrichment in × upon CdCl exposures (50 μM, 30 min to 24 h). The fungus-stimulated Cd in roots was significantly restricted by inhibitors of plasmalemma H-ATPases and Ca-permeable channels (CaPCs), but stimulated by an activator of plasmalemma H-ATPases. NaCl (100 mM) lowered the transient and steady-state Cd influx in roots and fungal mycelia. Noteworthy, colonization partly reverted the salt suppression of Cd uptake in poplar roots. EM fungus colonization upregulated transcription of plasmalemma H-ATPases (, , ) and annexins (, , ), which might mediate Cd conductance through CaPCs. EM roots retained relatively highly expressed and , thus facilitating Cd enrichment under co-occurring stress of cadmium and salinity. We conclude that ectomycorrhization of woody hyperaccumulator species such as poplar could improve phytoremediation of Cd in salt-affected areas.
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http://dx.doi.org/10.3390/ijms222111651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583747PMC
October 2021

Plasma membrane-localized SEM1 protein mediates sugar movement to sink rice tissues.

Plant J 2021 Nov 9. Epub 2021 Nov 9.

Joint CAAS/IRRI Laboratory for Photosynthetic Enhancement, Biotechnology Research Institute/National Key Facility for Genetic Resources and Gene Improvement, The Chinese Academy of Agricultural Sciences, Beijing, 100081, P. R. China.

The translocation of photosynthate carbohydrates, such as sucrose, is critical for plant growth and crop yield. Previous studies have revealed that sugar transporters, plasmodesmata and sieve plates act as important controllers in sucrose loading into and unloading from phloem in the vascular system. However, other pivotal steps for the regulation of sucrose movement remain largely elusive. In this study, characterization of two starch excesses in mesophyll (sem) mutants and dye and sucrose export assays were performed to provide insights into the regulatory networks that drive source-sink relations in rice. Map-based cloning identified two allelic mutations in a gene encoding a GLUCAN SYNTHASE-LIKE (GSL) protein, thus indicating a role for SEM1 in callose biosynthesis. Subcellular localization in rice showed that SEM1 localized to the plasma membrane. In situ expression analysis and GUS staining showed that SEM1 was mainly expressed in vascular phloem cells. Reduced sucrose transport was found in the sem1-1/1-2 mutant, which led to excessive starch accumulation in source leaves and inhibited photosynthesis. Paraffin section and transmission electron microscopy experiments revealed that less-developed vascular cells (VCs) in sem1-1/1-2 potentially disturbed sugar movement. Moreover, dye and sugar trafficking experiments revealed that aberrant VC development was the main reason for the pleiotropic phenotype of sem1-1/1-2. In total, efficient sucrose loading into the phloem benefits from an optional number of VCs with a large vacuole that could act as a buffer holding tank for sucrose passing from the vascular bundle sheath.
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http://dx.doi.org/10.1111/tpj.15573DOI Listing
November 2021

4-Iodopyrimidine Labeling Reveals Nuclear Translocation and Nuclease Activity for Both MIF and MIF2*.

Chemistry 2021 Nov 1. Epub 2021 Nov 1.

Department Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.

Macrophage migration inhibitory factor (MIF) and its homolog MIF2 (also known as D-dopachrome tautomerase or DDT) play key roles in cell growth and immune responses. MIF and MIF2 expression is dysregulated in cancers and neurodegenerative diseases. Accurate and convenient detection of MIF and MIF2 will facilitate research on their roles in cancer and other diseases. Herein, we report the development and application of a 4-iodopyrimidine based probe 8 for the selective labeling of MIF and MIF2. Probe 8 incorporates a fluorophore that allows in situ imaging of these two proteins. This enabled visualization of the translocation of MIF2 from the cytoplasm to the nucleus upon methylnitronitrosoguanidine stimulation of HeLa cells. This observation, combined with literature on nuclease activity for MIF, enabled the identification of nuclease activity for MIF2 on human genomic DNA.
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http://dx.doi.org/10.1002/chem.202103030DOI Listing
November 2021

The effect of cartilage decellularized extracellular matrix-chitosan compound on treating knee osteoarthritis in rats.

PeerJ 2021 12;9:e12188. Epub 2021 Oct 12.

Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China.

Knee osteoarthritis (KOA) refers to a common disease in orthopaedics, whereas effective treatments have been rarely developed. As indicated from existing studies, chondrocyte death, extracellular matrix degradation and subchondral bone injury are recognized as the pathological basis of KOA. The present study aimed to determine the therapeutic effect of decellularized extracellular matrix-chitosan (dECM-CS) compound on KOA. In this study, rat knee cartilage was decellularized, and a satisfactory decellularized extracellular matrix was developed. As suggested from the experiments, the rat chondrocytes co-cultured with allogeneic dECM grew effectively. According to the results of the alamar blue detection, dECM did not adversely affect the viability of rat chondrocytes, and dECM could up-regulate the genes related to the cartilage synthesis and metabolism. As reported from the animal experiments, dECM-CS compound could protect cartilage, alleviate knee joint pain in rats, significantly delay the progress of KOA in rats, and achieve high drug safety. In brief, dECM-CS compound shows a good therapeutic effect on KOA.
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http://dx.doi.org/10.7717/peerj.12188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519179PMC
October 2021

Analysis of Trend and Associated Factors of Neuropsychological Development of Infants and Toddlers Based on Longitudinal Data.

Children (Basel) 2021 Sep 28;8(10). Epub 2021 Sep 28.

School of Public Health, Fudan University, Shanghai 200433, China.

Objective: To explore the trend and associated factors of neuropsychological development of infants and toddlers in China.

Methods: A longitudinal study was conducted among 619 infants and toddlers (2914 person-times) aged 0 to 36 months from different provinces or cities in China from January 2013 to December 2019.

Results: The development age of each area increased with the extension of follow-up time, but this upward trend slowed down with physiological age at first measurement increasing. Among a low age group and each area, most of the development qualification rates in different follow-up periods were higher than that in the baseline ( < 0.05); however, many of them were not higher than that in the baseline among the medium or high age group ( > 0.05). For the areas of gross motor and self-care, the growth of qualification rate with the extension of follow-up was not obvious in the medium and high age group (both trend > 0.05). Some impact factors of development in all areas were identified.

Conclusions: The neuropsychological development delay of various areas of infants and toddlers, especially that of gross motor and self-care, should be paid early (within 1 years old) and constant attention. The impact of gender and maternal age on the development of young children has been further confirmed in the present study.
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http://dx.doi.org/10.3390/children8100866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535091PMC
September 2021

OsRELA Regulates Leaf Inclination by Repressing the Transcriptional Activity of OsLIC in Rice.

Front Plant Sci 2021 1;12:760041. Epub 2021 Oct 1.

Joint CAAS/IRRI Laboratory for Photosynthetic Enhancement, Biotechnology Research Institute/National Key Facility for Genetic Resources and Gene Improvement, Chinese Academy of Agricultural Sciences, Beijing, China.

Leaf angle is one of the most important agronomic traits in rice, and changes in leaf angle can alter plant architecture to affect photosynthetic efficiency and thus determine grain yield. Therefore, it is important to identify key genes controlling leaf angle and elucidate the molecular mechanisms to improve rice yield. We obtained a mutant with reduced leaf angle in rice by EMS mutagenesis, and map-based cloning revealed that encodes a protein of unknown function. Coincidentally, () was reported in a previous study with the same gene locus. analysis revealed that is involved in regulating the expression of and family genes. Biochemical and genetic analyses revealed that OsRELA is able to interact with OsLIC, a negative regulator of BR signaling, through its conserved C-terminal domain, which is essential for OsRELA function in rice. The binding of OsRELA can activate the expression of downstream genes repressed by OsLIC, such as , a positive regulator of leaf inclination in rice. Therefore, our results suggest that OsRELA can act as a transcriptional regulator and is involved in the regulation of leaf inclination by regulating the transcriptional activity of OsLIC.
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http://dx.doi.org/10.3389/fpls.2021.760041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519309PMC
October 2021

HDAC/MIF dual inhibitor inhibits NSCLC cell survival and proliferation by blocking the AKT pathway.

Bioorg Chem 2021 Dec 4;117:105396. Epub 2021 Oct 4.

Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, the Netherlands. Electronic address:

Non-small-cell lung carcinoma (NSCLC) is one of the most common forms of lung cancer, and a leading cause of cancer death among human beings. There is an urgent demand for novel therapeutics for the treatment of NSCLC to enhance the efficacy of the currently applied Tyrosine kinase inhibitors (TKIs) therapy and to overcome therapy-resistance. Here, we report a novel small-molecule inhibitor that simultaneously targets histone deacetylase (HDAC) and macrophage migration inhibitory factor (MIF). The HDAC/MIF dual inhibitor proved to be toxic for EGFR mutated (H1650, TKI-resistant) or knock out (A549 EGFR) NSCLC cell lines. Further experiments showed that HDAC inhibition inhibits cell survival and proliferation, while MIF inhibition downregulates pAKT or AKT expression level, which both interfere with cell survival. Furthermore, the combination treatment of TKI and HDAC/MIF dual inhibitor showed that the dual inhibitor enhanced TKI inhibitory efficacy, highlighting the advantages of HDAC/MIF dual inhibitor for more effective treatment of NSCLC.
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http://dx.doi.org/10.1016/j.bioorg.2021.105396DOI Listing
December 2021

Endocytic protein Pal1 regulates appressorium formation and is required for full virulence of Magnaporthe oryzae.

Mol Plant Pathol 2021 Oct 12. Epub 2021 Oct 12.

State Key Laboratory of Hybrid Rice, Hunan Hybrid Rice Research Center, Changsha, China.

Endocytosis plays key roles during infection of plant-pathogenic fungi, but its regulatory mechanisms are still largely unknown. Here, we identified a putative endocytosis-related gene, PAL1, which was highly expressed in appressorium of Magnaporthe oryzae, and was found to be important for appressorium formation and maturation. Deletion of PAL1 significantly reduced the virulence of M. oryzae due to defects in appressorial penetration and invasive growth in host cells. The Pal1 protein interacted and colocalized with the endocytosis protein Sla1, suggesting it is involved in endocytosis. The Δpal1 mutant was significantly reduced in appressorium formation, which was recovered by adding exogenous cAMP and 3-isobutyl-1-methylxanthine (IBMX). Moreover, the phosphorylation level of Pmk1 in Δpal1 was also reduced, suggesting Pal1 functions upstream of both the cAMP and Pmk1 signalling pathways. As a consequence, the utilization of glycogen and lipid, appressorial autophagy, actin ring formation, localization of septin proteins, as well as turgor accumulation were all affected in the Δpal1 mutant. Taken together, Pal1 regulates cAMP and the Pmk1 signalling pathway for appressorium formation and maturation to facilitate infection of M. oryzae.
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http://dx.doi.org/10.1111/mpp.13149DOI Listing
October 2021

Trend of Sudden Unexpected Death in Epilepsy Incidence Rate in Rural West China.

Front Neurol 2021 24;12:735201. Epub 2021 Sep 24.

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

To explore the trend of sudden unexpected death in epilepsy (SUDEP) incidence rate over time in rural west China. We scanned probable SUDEP patients from the epilepsy program between 2010 and 2019 in rural West China and performed a verbal autopsy for each eligible patient. We calculated the crude and sex-adjusted incidence rate of SUDEP per person-year over a calendar year and the year of follow-up. We calculated the incidence rate ratio with the Poisson model in STATA 12.0 and calculated the annual percentage change (APC) and average annual percentage change in Joinpoint Trend Analysis Software 4.8.0.1 to analyze the trend of SUDEP incidence rate. In 2010-2019, 44 probable SUDEPs were identified from 10,128 patients with a total person-year of 31,347. The crude and sex-adjusted incidence rates of SUDEP were 1.40 and 1.45%0. Twenty-five (56.8%) of the 44 probable SUDEPs had no generalized tonic-clonic seizure 3 months before their death. The incidence of probable SUDEP decreased significantly in the calendar year [APC = -11.7, 95% confidence interval (CI): -21.7 to -0.3] and in time of follow-up (average annual percentage change = -21.2, 95% CI: -34.3 to -5.4). Comparing the first 5 years in follow-up with the subsequent 3 years, the incidence rate of SUDEP decreased significantly (estimated incidence rate ratio = 0.4, 95% CI: 0.2 to 0.8). SUDEP happened to 1.4 cases per thousand patient-years in convulsive epilepsy in rural west China between 2010 and 2019. The incidence rate of SUDEP presented a downward trend over the time of follow-up.
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http://dx.doi.org/10.3389/fneur.2021.735201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498108PMC
September 2021

The incidence, clinical characteristics, and outcome of polytrauma patients with the combination of pulmonary contusion, flail chest and upper thoracic spinal injury.

Injury 2021 Oct 1. Epub 2021 Oct 1.

Division of Trauma Surgery, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Electronic address:

Background: Chest trauma was the third most common cause of death in polytrauma patients, accounting for 25% of all deaths from traumatic injury. Chest trauma involves in injury to the bony thorax, intrathoracic organs and thoracic medulla. This study aimed to investigate the incidence, clinical characteristics, and outcome of polytrauma patients with pulmonary contusion, flail chest and upper thoracic spinal injury.

Methods: Patients who met inclusion criteria were divided into groups: Pulmonary contusion group (PC); Pulmonary contusion and flail chest group (PC + FC); Pulmonary contusion and upper thoracic spinal cord injury group (PC + UTSCI); Thoracic trauma triad group (TTT): included patients with flail chest, pulmonary contusion and the upper thoracic spinal cord injury coexisted. Outcomes were determined, including 30-day mortality and 6-month mortality.

Results: A total 84 patients (2.0%) with TTT out of 4176 polytrauma patients presented to Tongji trauma center. There was no difference in mean ISS among PC + FC group, PC + UTSCI group and TTT group. Patients with TTT had a longer ICU stay (21.4 days vs. 7.5 and 6.2; p<0.01), relatively higher 30-day mortality (40.5% vs. 6.0% and 4.3%; p<0.01), and especially higher 6-month mortality (71.4% vs. 6.5%, 13.0%; p<0.01), compared to patients with PC + FC or with PC + UTSCI. The leading causes of death for patients with TTT were ARDS (44.1%) and pulmonary infection (26.5%) during first 30 days after admission. For those patients who died later than 30 days during the 6 months, the predominant underlying cause of death was MOF (53.8%).

Conclusions: Lethal triad of thoracic trauma (LTTT) were described in this study, which consisting of pulmonary contusion,flail chest and the upper thoracic spine cord injury. Like the classic "lethal triad", there was a synergy between the factors when they coexist, resulting in especially high mortality rates. Polytrauma patients with LTTT were presented relatively high 30-day mortality and 6 months mortality. We should pay much more attention to the patients with LTTT for further minimizing complications and mortality.
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http://dx.doi.org/10.1016/j.injury.2021.09.053DOI Listing
October 2021

[Effectiveness of three-dimensional printing artificial vertebral body and interbody fusion Cage in anterior cervical surgery].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Sep;35(9):1147-1154

Department of Orthopedics, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital), Taiyuan Shanxi, 030032, P.R.China.

Objective: To evaluate the effectiveness of three-dimensional (3D) printing artificial vertebral body and interbody fusion Cage in anterior cervical disectomy and fusion (ACCF) combined with anterior cervical corpectomy and fusion (ACDF).

Methods: The clinical data of 29 patients with multilevel cervical spondylotic myelopathy who underwent ACCF combined with ACDF between May 2018 and December 2019 were retrospectively analyzed. Among them, 13 patients were treated with 3D printing artificial vertebral body and 3D printing Cage as 3D printing group and 16 patients with ordinary titanium mesh Cage (TMC) and Cage as TMC group. There was no significant difference in gender, age, surgical segment, Nurick grade, disease duration, and preoperative Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, and Cobb angle of fusion segment between the two groups ( >0.05). The operation time, intraoperative blood loss, hospitalization stay, complications, and implant fusion at last follow-up were recorded and compared between the two groups; JOA score was used to evaluate neurological function before operation, immediately after operation, at 6 months after operation, and at last follow-up; VAS score was used to evaluate upper limb and neck pain. Cobb angle of fusion segment was measured and the difference between the last follow-up and the immediate after operation was calculated. The height of the anterior border (HAB) and the height of the posterior border (HPB) were measured immediately after operation, at 6 months after operation, and at last follow-up, and the subsidence of implant was calculated.

Results: The operation time of 3D printing group was significantly less than that of TMC group ( =3.336, =0.002); there was no significant difference in hospitalization stay and intraoperative blood loss between the two groups ( >0.05). All patients were followed up 12-19 months (mean, 16 months). There was no obvious complication in both groups. There were significant differences in JOA score, VAS score, and Cobb angle at each time point between the two groups ( <0.05). There was an interaction between time and group in the JOA score ( =3.705, =0.025). With time, the increase in JOA score was different between the 3D printing group and the TMC group, and the increase in the 3D printing group was greater. There was no interaction between time and group in the VAS score ( =3.038, =0.065), and there was no significant difference in the score at each time point between the two groups ( =0.173, =0.681). The time of the Cobb angle interacted with the group ( =15.581, =0.000). With time, the Cobb angle of the 3D printing group and the TMC group changed differently. Among them, the 3D printing group increased more and the TMC group decreased more. At last follow-up, there was no significant difference in the improvement rate of JOA score between the two groups ( =0.681, =0.502), but the Cobb angle difference of the 3D printing group was significantly smaller than that of the TMC group ( =5.754, =0.000). At last follow-up, the implant fusion rate of the 3D printing group and TMC group were 92.3% (12/13) and 87.5% (14/16), respectively, and the difference was not significant ( =1.000). The incidence of implant settlement in the 3D printing group and TMC group at 6 months after operation was 15.4% (2/13) and 18.8% (3/16), respectively, and at last follow-up were 30.8% (4/13) and 56.3% (9/16), respectively, the differences were not significant ( =1.000; =0.264). The difference of HAB and the difference of HPB in the 3D printing group at 6 months after operation and last follow-up were significantly lower than those in the TMC group ( <0.05).

Conclusion: For patients with multilevel cervical spondylotic myelopathy undergoing ACCF combined with ACDF, compared with TMC and Cage, 3D printing artificial vertebrae body and 3D printing Cage have the advantages of shorter operation time, better reduction of height loss of fusion vertebral body, and maintenance of cervical physiological curvature, the early effectiveness is better.
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http://dx.doi.org/10.7507/1002-1892.202103003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444133PMC
September 2021

Emerging bioelectrochemical technologies for biogas production and upgrading in cascading circular bioenergy systems.

iScience 2021 Sep 18;24(9):102998. Epub 2021 Aug 18.

MaREI Centre, Environmental Research Institute, School of Engineering, University College Cork, Cork T23XE10, Ireland.

Biomethane is suggested as an advanced biofuel for the hard-to-abate sectors such as heavy transport. However, future systems that optimize the resource and production of biomethane have yet to be definitively defined. This paper assesses the opportunity of integrating anaerobic digestion (AD) with three emerging bioelectrochemical technologies in a circular cascading bioeconomy, including for power-to-gas AD (P2G-AD), microbial electrolysis cell AD (MEC-AD), and AD microbial electrosynthesis (AD-MES). The mass and energy flow of the three bioelectrochemical systems are compared with the conventional AD amine scrubber system depending on the availability of renewable electricity. An energy balance assessment indicates that P2G-AD, MEC-AD, and AD-MES circular cascading bioelectrochemical systems gain positive energy outputs by using electricity that would have been curtailed or constrained (equivalent to a primary energy factor of zero). This analysis of technological innovation, aids in the design of future cascading circular biosystems to produce sustainable advanced biofuels.
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http://dx.doi.org/10.1016/j.isci.2021.102998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426204PMC
September 2021

An Artificial Neural Network Prediction Model for Posttraumatic Epilepsy: Retrospective Cohort Study.

J Med Internet Res 2021 08 19;23(8):e25090. Epub 2021 Aug 19.

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

Background: Posttraumatic epilepsy (PTE) is a common sequela after traumatic brain injury (TBI), and identifying high-risk patients with PTE is necessary for their better treatment. Although artificial neural network (ANN) prediction models have been reported and are superior to traditional models, the ANN prediction model for PTE is lacking.

Objective: We aim to train and validate an ANN model to anticipate the risks of PTE.

Methods: The training cohort was TBI patients registered at West China Hospital. We used a 5-fold cross-validation approach to train and test the ANN model to avoid overfitting; 21 independent variables were used as input neurons in the ANN models, using a back-propagation algorithm to minimize the loss function. Finally, we obtained sensitivity, specificity, and accuracy of each ANN model from the 5 rounds of cross-validation and compared the accuracy with a nomogram prediction model built in our previous work based on the same population. In addition, we evaluated the performance of the model using patients registered at Chengdu Shang Jin Nan Fu Hospital (testing cohort 1) and Sichuan Provincial People's Hospital (testing cohort 2) between January 1, 2013, and March 1, 2015.

Results: For the training cohort, we enrolled 1301 TBI patients from January 1, 2011, to December 31, 2017. The prevalence of PTE was 12.8% (166/1301, 95% CI 10.9%-14.6%). Of the TBI patients registered in testing cohort 1, PTE prevalence was 10.5% (44/421, 95% CI 7.5%-13.4%). Of the TBI patients registered in testing cohort 2, PTE prevalence was 6.1% (25/413, 95% CI 3.7%-8.4%). The results of the ANN model show that, the area under the receiver operating characteristic curve in the training cohort was 0.907 (95% CI 0.889-0.924), testing cohort 1 was 0.867 (95% CI 0.842-0.893), and testing cohort 2 was 0.859 (95% CI 0.826-0.890). Second, the average accuracy of the training cohort was 0.557 (95% CI 0.510-0.620), with 0.470 (95% CI 0.414-0.526) in testing cohort 1 and 0.344 (95% CI 0.287-0.401) in testing cohort 2. In addition, sensitivity, specificity, positive predictive values and negative predictors in the training cohort (testing cohort 1 and testing cohort 2) were 0.80 (0.83 and 0.80), 0.86 (0.80 and 0.84), 91% (85% and 78%), and 86% (80% and 83%), respectively. When calibrating this ANN model, Brier scored 0.121 in testing cohort 1 and 0.127 in testing cohort 2. Compared with the nomogram model, the ANN prediction model had a higher accuracy (P=.01).

Conclusions: This study shows that the ANN model can predict the risk of PTE and is superior to the risk estimated based on traditional statistical methods. However, the calibration of the model is a bit poor, and we need to calibrate it on a large sample size set and further improve the model.
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http://dx.doi.org/10.2196/25090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414301PMC
August 2021

Brain function and network features in patients with chronic epilepsy before and after antiseizure medication withdrawal.

Epilepsy Res 2021 Oct 14;176:106740. Epub 2021 Aug 14.

Epilepsy Center, Department of Neurology, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu, 610041, Sichuan Province, China. Electronic address:

Objectives: A considerable proportion of epilepsy patients who achieved long-term seizure freedom with standardized treatment of antiseizure medication will attempt to withdraw medications. Epilepsy is currently considered as a network disease, however, the characteristics of brain function and neural network before and after medication withdrawal remain to be discovered.

Methods: Resting-state functional magnetic resonance imaging was obtained for 32 healthy controls, 32 seizure-free patients initiating medication tapering (PG1 group), and 16 seizure-free patients that had completely discontinued medications (PG2 group). Amplitude of low-frequency fluctuation and regional homogeneity were calculated to measure local functional activity. Global and nodal metrics of small-world network were calculated based on Graph theory. One-way analysis of variance was applied to analyze intergroup difference, withpost hoc analysis being conducted for each pair of groups.

Results: Sex, age at scanning and other clinical variables showed no significant difference between groups. As compared to control, the amplitude of low-frequency fluctuation, regional homogeneity or nodal metrics of neural network in some brain areas were abnormal in the PG1 or PG2 group; when compared between patient groups, significant between-group differences were also found in the amplitude of low-frequency fluctuation, regional homogeneity or nodal metrics. But, the global metrics of neural network showed no differences among groups.

Conclusions: The global metrics of patients with long-term seizure freedom were normal either before or after antiseizure medication withdrawal, while the local functional activity and nodal metrics in some brain areas were abnormal and differed between before and after antiseizure medication withdrawal.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106740DOI Listing
October 2021

Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP.

BMC Genomics 2021 Aug 17;22(1):621. Epub 2021 Aug 17.

Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Lane 37 #, 610041, Chengdu, Sichuan, China.

Background: Long noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP.

Methods: The Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs.

Results: A total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively.

Conclusions: LncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.
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http://dx.doi.org/10.1186/s12864-021-07921-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369804PMC
August 2021

Identification of a Bromodomain-like Region in 15-Lipoxygenase-1 Explains Its Nuclear Localization.

Angew Chem Int Ed Engl 2021 09 31;60(40):21875-21883. Epub 2021 Aug 31.

Department Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, The Netherlands.

Lipoxygenase (LOX) activity provides oxidative lipid metabolites, which are involved in inflammatory disorders and tumorigenesis. Activity-based probes to detect the activity of LOX enzymes in their cellular context provide opportunities to explore LOX biology and LOX inhibition. Here, we developed Labelox B as a potent covalent LOX inhibitor for one-step activity-based labeling of proteins with LOX activity. Labelox B was used to establish an ELISA-based assay for affinity capture and antibody-based detection of specific LOX isoenzymes. Moreover, Labelox B enabled efficient activity-based labeling of endogenous LOXs in living cells. LOX proved to localize in the nucleus, which was rationalized by identification of a functional bromodomain-like consensus motif in 15-LOX-1. This indicates that 15-LOX-1 is not only involved in oxidative lipid metabolism, but also in chromatin binding, which suggests a potential role in chromatin modifications.
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http://dx.doi.org/10.1002/anie.202106968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518382PMC
September 2021

Incidence rate and risk factors of status epilepticus after stroke.

Seizure 2021 Oct 31;91:491-498. Epub 2021 Jul 31.

Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Lane 37 #, Chengdu, Sichuan 610041, China. Electronic address:

Purpose To evaluate the incidence rate and risk factors for status epilepticus (SE) after stroke (PSSE), including ischaemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods A meta-analysis was performed using relevant research from databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. The quality of the studies was evaluated by using the quality evaluation criteria of the Agency for Healthcare Research and Quality (AHRQ). All data were pooled by STATA 12.0 software for meta-analysis. Results The review considered 1650 articles, and 17 articles with 2821 instances of SE among 1088087 instances of stroke were included. The incidence rate of SE after stroke was 6.90 per 1000 total strokes (95% CI: 5.58-8.22). By subgroup analysis of SE, the rates were 33.85‰ (95% CI: 13.77-53.94) for non-convulsive status epilepticus (NCSE) and 2.42‰ (95%CI: 1.66-3.19) for generalized convulsive status epilepticus (GCSE). Age, sex, and presence of atrial fibrillation showed no significant difference between the SE group and the non-SE group after stroke. Hypertension and diabetes are associated with a decreased rate of SE. However, African American race, alcohol abuse, and renal disease are associated with an increased rate of SE. Significance There were approximately 6.9 patients with status epilepticus per 1000 strokes. NCSE is more common after stroke and needs more attention. African American race, alcohol abuse and renal disease may be risk factors for PSSE.
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http://dx.doi.org/10.1016/j.seizure.2021.07.029DOI Listing
October 2021

Functional connectivity of the thalamocortical circuit in patients with seizure relapse after antiseizure medication withdrawal.

Epilepsia 2021 Oct 3;62(10):2463-2473. Epub 2021 Aug 3.

Epilepsy Center, Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

Objective: To characterize the features of thalamocortical functional connectivity during seizure recurrence at the time of antiseizure medication (ASM) withdrawal.

Methods: Patients with chronic epilepsy who attempted to discontinue medications were prospectively registered and followed up; 19 patients remained seizure-free (SF-group), 18 patients had seizure relapses (SR-group) after ASM withdrawal, and 28 healthy controls were recruited. Resting-state functional magnetic resonance imaging was performed before ASM withdrawal. Thalamus subdivisions were set as seeds to calculate voxelwise functional connectivity. Partial correlation analysis between functional connectivity and clinical variables was performed. A support vector machine was used to assess the predictive ability of the specific functional connectivity for seizure relapse.

Results: The within-group comparison indicated that the SR-group had more extensive functional connectivity than the SF-group; the left inferior pulvinar, left medial pulvinar, and right anterior pulvinar showed a significantly stronger functional connection with the precuneus in the SR-group than in the SF-group (Gaussian random field correction, voxel-level p < .001 and cluster-level p < .05). In the SR-group, a positive correlation was found between the left inferior pulvinar-precuneus connectivity and the active period (r = .46, p = .05), seizure-free period (r = .67, p = .002), and disease duration (r = .53, p = .02), and between the left medial pulvinar-precuneus connectivity and the seizure-free period (r = .58, p = .01). The combination of these thalamocortical connections showed a high predictive ability, with an area under the curve of .92 and accuracy of .90 (p = .01).

Significance: This study determined distinct features of thalamocortical functional connectivity at the time of ASM withdrawal in patients with and without seizure relapse, showing a potential for predicting seizure outcomes following ASM withdrawal.
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http://dx.doi.org/10.1111/epi.17014DOI Listing
October 2021

Synergistic improvement of N-acetylglucosamine production by engineering transcription factors and balancing redox cofactors.

Metab Eng 2021 09 28;67:330-346. Epub 2021 Jul 28.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China; Science Center for Future Foods, Ministry of Education, Jiangnan University, Wuxi, 214122, China. Electronic address:

The regulation of single gene transcription level in the metabolic pathway is often failed to significantly improve the titer of the target product, and even leads to the imbalance of carbon/nitrogen metabolic network and cofactor network. Global transcription machinery engineering (gTME) can activate or inhibit the synergistic expression of multiple genes in specific metabolic pathways, so transcription factors with specific functions can be expressed according to different metabolic regulation requirements, thus effectively increasing the synthesis of target metabolites. In addition, maintaining intracellular redox balance through cofactor engineering can realize the self-balance of cofactors and promote the efficient synthesis of target products. In this study, we rebalanced the central carbon/nitrogen metabolism and redox metabolism of Corynebacterium glutamicum S9114 by gTME and redox cofactors engineering to promote the production of the nutraceutical N-acetylglucosamine (GlcNAc). Firstly, it was found that the overexpression of the transcription factor RamA can promote GlcNAc synthesis, and the titer was further improved to 16 g/L in shake flask by using a mutant RamA (RamAM). Secondly, a CRISPR interference (CRISPRi) system based on dCpf1 was developed and used to inhibit the expression of global negative transcriptional regulators of GlcNAc synthesis, which promoted the GlcNAc titer to 27.5 g/L. Thirdly, the cofactor specificity of the key enzymes in GlcNAc synthesis pathway was changed by rational protein engineering, and the titer of GlcNAc in shake flask was increased to 36.9 g/L. Finally, the production of GlcNAc was scaled up in a 50-L fermentor, and the titer reached 117.1 ± 1.9 g/L, which was 6.62 times that of the control group (17.7 ± 0.4 g/L), and the yield was increased from 0.19 g/g to 0.31 g/g glucose. The results obtained here highlight the importance of engineering the global regulation of central carbon/nitrogen metabolism and redox metabolism to improve the production performance of microbial cell factories.
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http://dx.doi.org/10.1016/j.ymben.2021.07.012DOI Listing
September 2021

Comparative Secretome Analysis of Magnaporthe oryzae Identified Proteins Involved in Virulence and Cell Wall Integrity.

Genomics Proteomics Bioinformatics 2021 Jul 17. Epub 2021 Jul 17.

State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Pest Monitoring and Green Management, China Agricultural University, Beijing 100193, China. Electronic address:

Plant fungal pathogens secrete numerous proteins into the apoplast at the plant-fungus contact sites to facilitate colonization. Only a few secretory proteins were functionally characterized in Magnaporthe oryzae, the fungal pathogen causing rice blast disease worldwide. Asparagine-linked glycosylation 3 (Alg3) is an α-1, 3-mannosyltransferase functioning in the N-glycan synthesis of N-glycosylated secretory proteins. Fungal pathogenicity and cell wall integrity are impaired in Δalg3 mutants, but the secreted proteins affected in Δalg3 mutants are largely unknown. In this study, we compared the secretome of wild-type and Δalg3 mutants and identified 51 proteins that require Alg3 for proper secretion. These proteins are predicted to be involved in metabolic processes, interspecies interactions, cell wall organization, and response to chemicals. Nine proteins were selected for further validation. We found that these proteins were localized at the apoplastic region surrounding the fungal infection hyphae. Moreover, the N-glycosylation of these proteins was significantly changed in the Δalg3 mutant, leading to the decreased protein secretion and abnormal protein localization. Furthermore, we tested the biological function of two genes, INV1 encoding invertase 1, a secreted invertase and AMCase encoding acid mammalian chinitase, a secreted chitinase. The fungal virulence was significantly reduced, and the cell wall integrity was altered in the Δinv1 and Δamcase mutant strains. Moreover, the N-glycosylation is essential for the function and secretion of AMCase. Comparative secretome analysis of M. oryzae identified N-glycosylated secretory proteins that function in fungal virulence and cell wall integrity.
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http://dx.doi.org/10.1016/j.gpb.2021.02.007DOI Listing
July 2021

Brain functional and structural characteristics of patients with seizure recurrence following drug withdrawal.

Neuroradiology 2021 Dec 1;63(12):2087-2097. Epub 2021 Jul 1.

From the Epilepsy Center, Department of Neurology, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu, 610041, Sichuan Province, China.

Purpose: We aimed to analyze the characteristics of brain function and microstructure linked to epilepsy relapse after drug withdrawal in patients with focal epilepsy.

Methods: Resting-state functional magnetic resonance imaging and high-resolution T1-weighted images were acquired within 1 month prior to drug withdrawal from 15 patients who did not have epilepsy relapse (PER - group) and 16 patients who subsequently had epilepsy relapse (PER + group). Additionally, 23 healthy participants undergoing the same scanning protocol were included as controls. Fractional amplitude of low-frequency fluctuation (fALFF) and gray matter density (GMD) were compared among groups. Subgroup and correlation analyses were also performed.

Results: There were no significant differences in fALFF between patient groups, but the PER + group showed lower GMD in the bilateral calcarine, left precuneus, and right superior temporal gyrus than the PER - group (Gaussian random field correction, voxel-level P < 0.001 and cluster-level P < 0.05). Both increased seizure number and polytherapy were associated with lower GMD; also, patients using other antiseizure medications showed lower GMD than those using only levetiracetam (Gaussian random field correction, voxel-level P < 0.001, and cluster-level P < 0.05). The active period and disease duration showed both positive and negative correlations with GMD, while the seizure-free period mainly showed positive correlations with GMD (uncorrected, P < 0.001).

Conclusion: Gray matter microstructure, but not local functional activity, showed distinct characteristics between patients with and without epilepsy relapse and may serve as a potential biomarker for predicting seizure recurrence upon drug withdrawal.
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http://dx.doi.org/10.1007/s00234-021-02755-2DOI Listing
December 2021

A Decade of CRISPR Gene Editing in China and Beyond: A Scientometric Landscape.

CRISPR J 2021 06;4(3):313-320

Zhejiang Academy of Science and Technology Information, Hangzhou, China; and Hangzhou, China.

Since its Nobel Prize-winning breakthrough in 2012, CRISPR-Cas-based gene-editing system has emerged as one of the most promising biotechnologies in decades. In this article, we present an objective and comprehensive evaluation of CRISPR-based gene-editing technologies, including base editing and prime editing, based on the bibliometric analysis of 22,902 published records. We also assessed the status of CRISPR gene-editing technologies in academia from 2010 to 2020 globally, with respect to countries, institutions, and researchers, and used text clustering methods to assess technical trends and research hotspots. Our results indicate, not surprisingly, that this is a thriving and prominent area of research. By comparing the relevance and growth of CRISPR gene-editing technologies in China with other countries by several metrics, we show that the Chinese scientific community attaches considerable importance to the field of plant genome engineering, with more scholars from agricultural sectors than other sectors.
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http://dx.doi.org/10.1089/crispr.2020.0148DOI Listing
June 2021

Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies.

Pathogens 2021 May 11;10(5). Epub 2021 May 11.

Division of Trauma & Surgical Critical Care, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has been recently considered a systemic disorder leading to the procoagulant state. Preliminary studies have shown that SARS-CoV-2 can infect endothelial cells, and extensive evidence of inflammation and endothelial dysfunction has been found in advanced COVID-19. Endothelial cells play a critical role in many physiological processes, such as controlling blood fluidity, leukocyte activation, adhesion, platelet adhesion and aggregation, and transmigration. Therefore, it is reasonable to think that endothelial dysfunction leads to vascular dysfunction, immune thrombosis, and inflammation associated with COVID-19. This article summarizes the association of endothelial dysfunction and SARS-CoV-2 infection and its therapeutic strategies.
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http://dx.doi.org/10.3390/pathogens10050582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151812PMC
May 2021

Prp19-associated splicing factor Cwf15 regulates fungal virulence and development in the rice blast fungus.

Environ Microbiol 2021 Oct 10;23(10):5901-5916. Epub 2021 Jun 10.

Ministry of Agriculture and Rural Affairs Key Laboratory of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing, 100193, China.

The splicing factor Cwf15 is an essential component of the Prp19-associated component of the spliceosome and regulates intron splicing in several model species, including yeasts and human cells. However, the roles of Cwf15 remain unexplored in plant pathogenic fungi. Here, we report that MoCWF15 in the rice blast fungus Magnaporthe oryzae is non-essential to viability and important to fungal virulence, growth and conidiation. MoCwf15 contains a putative nuclear localization signal (NLS) and is localized into the nucleus. The NLS sequence but not the predicted phosphorylation site or two sumoylation sites was essential for the biological functions of MoCwf15. Importantly, MoCwf15 physically interacted with the Prp19-associated splicing factors MoCwf4, MoSsa1 and MoCyp1, and negatively regulated protein accumulations of MoCyp1 and MoCwf4. Furthermore, with the deletion of MoCWF15, aberrant intron splicing occurred in near 400 genes, 20 of which were important to the fungal development and virulence. Taken together, MoCWF15 regulates fungal growth and infection-related development by modulating the intron splicing efficiency of a subset of genes in the rice blast fungus.
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http://dx.doi.org/10.1111/1462-2920.15616DOI Listing
October 2021
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