Publications by authors named "Ke Xu"

1,572 Publications

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Prognostic Value of Pre-Treatment CT Radiomics and Clinical Factors for the Overall Survival of Advanced (IIIB-IV) Lung Adenocarcinoma Patients.

Front Oncol 2021 28;11:628982. Epub 2021 May 28.

GE Healthcare, Beijing, China.

Purpose: The purpose of this study was to investigate the prognostic value of pre-treatment CT radiomics and clinical factors for the overall survival (OS) of advanced (IIIB-IV) lung adenocarcinoma patients.

Methods: This study involved 165 patients with advanced lung adenocarcinoma. The Lasso-Cox regression model was used for feature selection and radiomics signature building. Then a clinical model was built based on clinical factors; a combined model in the form of nomogram was constructed with both clinical factors and the radiomics signature. Harrell's concordance index (C-Index) and Receiver operating characteristic (ROC) curves at cut-off time points of 1-, 2-, and 3- year were used to estimate and compare the predictive ability of all three models. Finally, the discriminatory ability and calibration of the nomogram were analyzed.

Results: Thirteen significant features were selected to build the radiomics signature whose C-indexes were 0.746 (95% CI, 0.699 to 0.792) in the training cohort and 0.677 (95% CI, 0.597 to 0.766) in the validation cohort. The C-indexes of combined model achieved 0.799 (95% CI, 0.757 to 0.84) in the training cohort and 0.733 (95% CI, 0.656 to 0.81) in the validation cohort, which outperformed the clinical model and radiomics signature. Moreover, the areas under the curve (AUCs) of the radiomic signature for 2-year prediction was superior to that of the clinical model. The combined model had the best AUCs for 2- and 3-year predictions.

Conclusions: Radiomic signatures and clinical factors have prognostic value for OS in advanced (IIIB-IV) lung adenocarcinoma patients. The optimal model should be selected according to different cut-off time points in clinical application.
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http://dx.doi.org/10.3389/fonc.2021.628982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193844PMC
May 2021

Prognostic value of histopathologic pattern for long-term surgical outcomes of 198 patients with confirmed mesial temporal lobe epilepsy.

Hum Pathol 2021 Jun 10. Epub 2021 Jun 10.

Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Epilepsy. Electronic address:

Objective: Hippocampal sclerosis (HS) is the most common neuropathologic findings in patients with intractable temporal lobe epilepsy (TLE). The international league against epilepsy (ILAE) has proposed a new classification of HS based on pyramidal cell loss on different subfields to facilitate the study of HS pathology in patients after ATL, and the influence of these HS patterns on the prognosis of TLE patients is contradictory. This study aims to investigate the relationship between different HS subtypes and postoperative seizure outcomes for intractable TLE patients.

Methods: From January 2008 to December 2018, we retrospectively reviewed 198 TLE patients with ATL surgery, and all patients had a complete preoperative evaluation, a specimen of hippocampal tissue after surgery, cognitive test after surgery, and more than 2 years of postoperative follow-up.

Results: The main findings were as following: 1) temporal neocortical gray matter heterotopia (GMH) were more common in the no-HS group; 2) HS type 1 was associated with a longer duration of epilepsy; 3) history of meningitis was the independent predictor of HS type 1; 4) no-HS patients experienced worse postoperative seizure outcomes than those with HS type1 and type 2, whereas no difference in seizure outcomes was obtained between HS type 1 and type 2; 5) no-HS patients were at increased risk for verbal memory decline following left hippocampal resection.

Significance: The HS subtypes were associated with the prognosis of TLE patients, and other variables were the predictors of different HS types. Further study was to identify the HS subtypes by non-invasive evaluation to approve better postoperative outcomes.
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http://dx.doi.org/10.1016/j.humpath.2021.05.011DOI Listing
June 2021

Preparation of adsorbent based on water treatment residuals and chitosan by homogeneous method with freeze-drying and its As(V) removal performance.

Int J Biol Macromol 2021 Jun 9. Epub 2021 Jun 9.

Key Laboratory of Water Quality Science and Water Environment Recovery Engineering, Beijing University of Technology, Beijing 100124, China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

Although the chitosan-WTRs particulate adsorbent prepared by embedding method has been proved to have arsenic adsorption capacity, the capacity of it is greatly weakened compared with the original water treatment residuals (WTRs). In this study, WTRs and chitosan were used as raw materials to prepare a new kind of adsorbent beads by a homogeneous method. At the same time, in order to enhance the adsorption capacity and reduce the limitation of kinetics, freeze-drying method was chosen to dry the adsorbent. The WTRs-chitosan beads by homogeneous method (WCB) were characterized by SEM, XRD, XPS and other methods. According to the characterization results, there are regularly arranged pores inside the particles, and the iron in the particles mainly exists in the form of amorphous iron oxyhydroxide. According to the results of batch experiment, the pseudo-second-order kinetic model has a higher degree of fit, indicating that the WCB adsorbs As(V) mainly by chemical adsorption. The maximum adsorption capacity estimated from the Langmuir isotherm model is 42.083 mg/g, which is almost same as the WTRs. Weak acid and neutral conditions are conducive to adsorption, while alkaline conditions have a significant inhibitory effect on arsenic adsorption.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.032DOI Listing
June 2021

Review of Recent Progress on Vertical GaN-Based PN Diodes.

Nanoscale Res Lett 2021 Jun 7;16(1):101. Epub 2021 Jun 7.

College of Materials Science and Engineering, Shenzhen University-Hanshan Normal University Postdoctoral Workstation, Shenzhen University, Shenzhen, 518060, China.

As a representative wide bandgap semiconductor material, gallium nitride (GaN) has attracted increasing attention because of its superior material properties (e.g., high electron mobility, high electron saturation velocity, and critical electric field). Vertical GaN devices have been investigated, are regarded as one of the most promising candidates for power electronics application, and are characterized by the capacity for high voltage, high current, and high breakdown voltage. Among those devices, vertical GaN-based PN junction diode (PND) has been considerably investigated and shows great performance progress on the basis of high epitaxy quality and device structure design. However, its device epitaxy quality requires further improvement. In terms of device electric performance, the electrical field crowding effect at the device edge is an urgent issue, which results in premature breakdown and limits the releasing superiorities of the GaN material, but is currently alleviated by edge termination. This review emphasizes the advances in material epitaxial growth and edge terminal techniques, followed by the exploration of the current GaN developments and potential advantages over silicon carbon (SiC) for materials and devices, the differences between GaN Schottky barrier diodes (SBDs) and PNDs as regards mechanisms and features, and the advantages of vertical devices over their lateral counterparts. Then, the review provides an outlook and reveals the design trend of vertical GaN PND utilized for a power system, including with an inchoate vertical GaN PND.
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http://dx.doi.org/10.1186/s11671-021-03554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184903PMC
June 2021

Review of Recent Progress on Vertical GaN-Based PN Diodes.

Nanoscale Res Lett 2021 Jun 7;16(1):101. Epub 2021 Jun 7.

College of Materials Science and Engineering, Shenzhen University-Hanshan Normal University Postdoctoral Workstation, Shenzhen University, Shenzhen, 518060, China.

As a representative wide bandgap semiconductor material, gallium nitride (GaN) has attracted increasing attention because of its superior material properties (e.g., high electron mobility, high electron saturation velocity, and critical electric field). Vertical GaN devices have been investigated, are regarded as one of the most promising candidates for power electronics application, and are characterized by the capacity for high voltage, high current, and high breakdown voltage. Among those devices, vertical GaN-based PN junction diode (PND) has been considerably investigated and shows great performance progress on the basis of high epitaxy quality and device structure design. However, its device epitaxy quality requires further improvement. In terms of device electric performance, the electrical field crowding effect at the device edge is an urgent issue, which results in premature breakdown and limits the releasing superiorities of the GaN material, but is currently alleviated by edge termination. This review emphasizes the advances in material epitaxial growth and edge terminal techniques, followed by the exploration of the current GaN developments and potential advantages over silicon carbon (SiC) for materials and devices, the differences between GaN Schottky barrier diodes (SBDs) and PNDs as regards mechanisms and features, and the advantages of vertical devices over their lateral counterparts. Then, the review provides an outlook and reveals the design trend of vertical GaN PND utilized for a power system, including with an inchoate vertical GaN PND.
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http://dx.doi.org/10.1186/s11671-021-03554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184903PMC
June 2021

A Study on Supply-Demand Satisfaction of Community-Based Senior Care Combined with the Psychological Perception of the Elderly.

Healthcare (Basel) 2021 May 29;9(6). Epub 2021 May 29.

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

Based on Maslow's hierarchy of needs theory and customer satisfaction theory, we constructed a satisfaction model for supply-demand satisfaction for community-based senior care (SSCSC) combined with the psychological perspective of the elderly, and four dimensions of basic living needs (BLNs), living environment (LE), personal traits (PTs), and livability for the aged (LA) were selected to construct the model. The data were obtained from 296 questionnaires from seniors over 50 years old (or completed by relatives on their behalf, according to their actual situation). Twenty-two observed variables were selected for the five latent variables, and their interactions were explored using structural equation modeling. The results showed that LA was the most significant factor influencing SSCSC, and it was followed by BLNs and LE. PTs did not show a direct effect on LA, but they could have an indirect effect on SSCSC through influencing BLNs and LE. Based on the current state of community aging satisfaction, we propose to establish a community elderly care service system based on the basic needs of the elderly population, providing differentiated and refined elderly care services and improving the level of aging-friendly communities. This study provides references for the government to formulate relevant policies and other supply entities to make strategic decisions and has important implications for further enhancing community elderly services to become an important part of the social security system for the elderly.
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http://dx.doi.org/10.3390/healthcare9060643DOI Listing
May 2021

Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation.

Front Pharmacol 2021 14;12:672054. Epub 2021 May 14.

Department of Joint Surgery, Xi'an Jiaotong University Affiliated HongHui Hospital, Xi'an, China.

Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent hyperplasia of the synovial membrane and progressive erosion of articular cartilage. Disequilibrium between the proliferation and death of RA fibroblast-like synoviocytes (RA-FLSs) is the critical factor in progression of RA. Naringin has been reported to exert anti-inflammatory and antioxidant effect in acute and chronic animal models of RA. However, the therapeutic effect and underlying mechanisms of naringin in human RA-FLS remain unclear. Based on network pharmacology, the corresponding targets of naringin were identified using SwissTargetPrediction database, STITCH database, and Comparative Toxicogenomics Database. Deferentially expressed genes (DEGs) in RA were obtained from the GEO database. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to pathogenesis of RA were integrated manually. Further, studies were carried out based on network pharmacology. 99 target genes were intersected between targets of naringin and DEGs. The PPI network and topological analysis indicated that IL-6, MAPK8, MMP-9, TNF, and MAPK1 shared the highest centrality among all. GO analysis and KEGG analysis indicated that target genes were mostly enriched in (hsa05200) pathways in cancer, (hsa05161) hepatitis B, (hsa04380) osteoclast differentiation, (hsa04151) PI3K-Akt signaling pathway, and (hsa05142) Chagas disease (American trypanosomiasis). studies revealed that naringin exposure was found to promote apoptosis of RA-FLS, increased the activation of caspase-3, and increased the ratio of Bax/Bcl-2 in a dose-dependent manner. Furthermore, treatment of naringin attenuated the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in TNF-ɑ-induced RA-FLS. Moreover, treatment of naringin inhibited the phosphorylation of Akt and ERK in RA-FLS. Network pharmacology provides a predicative strategy to investigate the therapeutic effects and mechanisms of herbs and compounds. Naringin inhibits inflammation and MMPs production and promotes apoptosis in RA-FLS PI3K/Akt and MAPK/ERK signaling pathways.
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http://dx.doi.org/10.3389/fphar.2021.672054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160516PMC
May 2021

Potential Alterations of Functional Connectivity Analysis in the Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Neural Plast 2021 7;2021:6690414. Epub 2021 May 7.

Department of Urology, Huashan Hospital, Fudan University, 12 Central Urumqi Rd, Shanghai 200040, China.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, but its pathogenesis remains unclear. As a kind of chronic pain which the patients suffered for more than 3 months, we investigated the influence on patients' brain functional connectivity in resting state.

Methods: We recruited a cohort of 18 right-handed male patients with CP/CPPS and 21 healthy male right-handed age-matched controls. Their resting-state fMRI data and structural MRI data were preprocessed and processed by RESTPlus V1.22. To assess the integrity of the default mode network (DMN), we utilized the voxel-wised analysis that we set medial prefrontal cortex (mPFC) and posterior cingulate gyrus (PCC) as seed points to compare the global functional connectivity (FC) strength.

Results: Compared with healthy control, the FC strength between left mPFC and posterior DMN decreased in the group of CP/CPPS ( < 0.05, GFR correction, voxel < 0.01, cluster < 0.05), and the FC strength between the left anterior cerebellar lobe and posterior DMN increased ( < 0.05, GFR correction, voxel < 0.01, cluster < 0.05). In the patient group, there was a positive correlation between the increased FC strength and the score of the Hospital Anxiety and Depression Scale (HADS) anxiety subscale ( = 0.5509, = 0.0178) in the left anterior cerebellar lobe, a negative correlation between the decreased FC strength and the score of the National Institutes of Health Chronic Prostatitis Symptom Index ( = -0.6281, = 0.0053) in the area of left mPFC, and a negative correlation between the decreased FC strength and the score of HADS anxiety subscale ( = -0.5252, = 0.0252).

Conclusion: Patients with CP/CPPS had alterations in brain function, which consisted of the default mode network's compromised integrity. These alterations might play a crucial role in the pathogenesis and development of CP/CPPS.
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http://dx.doi.org/10.1155/2021/6690414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121565PMC
May 2021

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis.

Nat Neurosci 2021 May 24. Epub 2021 May 24.

Institute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.

Single-cell transcriptomics provide a systematic map of gene expression in different human cell types. The next challenge is to systematically understand cell-type-specific gene function. The integration of CRISPR-based functional genomics and stem cell technology enables the scalable interrogation of gene function in differentiated human cells. Here we present the first genome-wide CRISPR interference and CRISPR activation screens in human neurons. We uncover pathways controlling neuronal response to chronic oxidative stress, which is implicated in neurodegenerative diseases. Unexpectedly, knockdown of the lysosomal protein prosaposin strongly sensitizes neurons, but not other cell types, to oxidative stress by triggering the formation of lipofuscin, a hallmark of aging, which traps iron, generating reactive oxygen species and triggering ferroptosis. We also determine transcriptomic changes in neurons after perturbation of genes linked to neurodegenerative diseases. To enable the systematic comparison of gene function across different human cell types, we establish a data commons named CRISPRbrain.
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http://dx.doi.org/10.1038/s41593-021-00862-0DOI Listing
May 2021

GBP2 as a potential prognostic biomarker in pancreatic adenocarcinoma.

PeerJ 2021 11;9:e11423. Epub 2021 May 11.

Department of Oncology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

Background: Pancreatic adenocarcinoma (PAAD) is a disease with atypical symptoms, an unfavorable response to therapy, and a poor outcome. Abnormal guanylate-binding proteins (GBPs) play an important role in the host's defense against viral infection and may be related to carcinogenesis. In this study, we sought to determine the relationship between GBP2 expression and phenotype in patients with PAAD and explored the possible underlying biological mechanism.

Method: We analyzed the expression of GBP2 in PAAD tissues using a multiple gene expression database and a cohort of 42 PAAD patients. We evaluated GBP2's prognostic value using Kaplan-Meier analysis and the Cox regression model. GO and KEGG enrichment analysis, co-expression analysis, and GSEA were performed to illustrate the possible underlying biological mechanism. CIBERSORT and the relative expression of immune checkpoints were used to estimate the relationship between GBP2 expression and tumor immunology.

Result: GBP2 was remarkably overexpressed in PAAD tissue. The overexpression of GBP2 was correlated with an advanced T stage and poor overall survival (OS) and GBP2 expression was an independent risk factor for OS in PAAD patients. Functional analysis demonstrated that positively co-expressed genes of GBP2 were closely associated with pathways in cancer and the NOD-like receptor signaling pathway. Most of the characteristic immune checkpoints, including PDCD1, PDCDL1, CTLA4, CD80, TIGIT, LAG3, IDO2, and VISTA, were significantly expressed in the high-GBP2 expression group compared with the low-GBP2 expression group.

Conclusion: GBP2 acted as a potential prognostic biomarker and was associated with immune infiltration and the expression of immune checkpoints in PAAD.
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http://dx.doi.org/10.7717/peerj.11423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121056PMC
May 2021

Photodynamic Therapy Synergize with PD-L1 Checkpoint Blockade for Immunotherapy of Colorectal Cancer by Multifunctional Nanoparticle.

Mol Ther 2021 May 20. Epub 2021 May 20.

Interventional Cancer Institute of Chinese Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China; Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Hefei 230032, China; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Wenzhou Institute of Shanghai University, Wenzhou 325000, China. Electronic address:

Checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have been shown to be extraordinarily effective, but their durable response rate remains low, especially in colorectal cancer (CRC). Recent studies have shown that photodynamic therapy (PDT) which could effectively enhance PD-L1 blockade therapeutical effect, while its reason is still unclear. Here, we reported the use of multifunctional nanoparticles loaded with the photosensitize mTHPC ([email protected]/T-RGD NPs) mediated PDT treatment to potentiate the anti-tumor efficacy of PD-L1 blockade for CRC treatment, and investigated the underlying mechanisms of PDT enhancing PD-L1 blockade therapeutical effect in this combination therapy. In this study, the [email protected]/T-RGD NPs under the 660 nm NIR laser could kill tumor cells by inducing apoptosis and/or necrosis and stimulate systemic immune response, which could be further promoted by the PD-L1 blockade to inhibit primary and distance tumors growth, as well as building long-term host immunological memory to prevent tumor reoccurrence. Furthermore, we detected [email protected]/T-RGD NPs mediated PDT sensitizes tumors to PD-L1 blockade therapy mainly because PDT mediated hypoxia could induce HIF-1α signaling pathway that up-regulate PD-L1 expression in CRC. Taken together, our work demonstrates the [email protected]/T-RGD NPs mediated PDT is a promising strategy, which may potentiate response rate of anti-PD-L1 checkpoint blockade immunotherapies in CRC.
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http://dx.doi.org/10.1016/j.ymthe.2021.05.017DOI Listing
May 2021

Mental health among pregnant women under public health interventions during COVID-19 outbreak in Wuhan, China.

Psychiatry Res 2021 07 1;301:113977. Epub 2021 May 1.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, Hubei, China. Electronic address:

Coronavirus disease 2019 (COVID-19) has become a pandemic. As the first city struck by the COVID-19 outbreak, Wuhan had implemented unprecedented public health interventions. The mental health of pregnant women during these anti-epidemic controls remains unknown. A total of 274 pregnant women living in Wuhan during the COVID-19 outbreak took part in our investigation online. The data on mental health conditions were evaluated using Edinburgh Postnatal Depression Scale (EPDS), Self-Rating Anxiety Scale (SAS), Chinese Perceived Stress Scale (CPSS), and Pittsburgh Sleep Quality Index (PSQI). We also collected the information on physical health status and precautionary measures against COVID-19. The prevalence of depression, anxiety, stress, and poor sleep quality was 16.1%, 13.9%, 42.7%, 37.6%, respectively. Comparing to SAS, PSQI score in pregnant women who participated in the survey after April 8 (date of Wuhan reopening), those data collected before April 8 were significantly higher. High levels of stress, severe health concerns over the fetus, and poor hygienic practices were negatively associated with mental health conditions. In conclusion, a large proportion of pregnant women reported psychological symptoms during the epidemic, which negatively related to the severe health concerns over fetus and poor hygienic practices. More psychological support during the epidemic would promote maternal mental well-being.
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http://dx.doi.org/10.1016/j.psychres.2021.113977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088032PMC
July 2021

The Anti-Tumor Effect and Mechanism of Triterpenoids in Mill. on Reversing Effector CD8+ T-cells Dysfunction by Targeting Glycolysis Pathways in Colorectal Cancer.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211017219

Southeast University, Nanjing, Jiangsu, China.

Mill. is a traditional Chinese medicine (TCM) which is commonly used for cancer treatments. Our previous work had proven that triterpenoids of (TER) could effectively regulate glycolysis involved in colorectal cancer (CRC) and play an important role in the prevention of T-cells dysfunction. This study aimed to systematically investigate the effects and mechanisms of TER on glucose metabolism in CRC, while the regulatory mechanisms of TER on restoring T-cells function and activity in CRC were explored as well. The extract of triterpenoids from was obtained, and production of lactic acid and glucose uptake were assayed. Also, the expression of CD8+ T-cells surface markers, cytokines secreted by CD8+ T cells, and the expression of key glycolytic enzymes and glucose deprivation induced by tumor cells were further examined. Notably, results showed that TER prevented the dysfunction in CD8+ T cells by enhancing mTOR activity and subsequent cellular metabolism. Furthermore, our findings also demonstrated that TER promoted glycolytic gene expression in CD8+ T cells in vivo, and significantly inhibited tumor growth. Altogether, our studies suggested that TER not only reversed effector CD8+ T-cells dysfunction and enhanced T-cells recognition, but also improved tumor microenvironment, thereby providing new insight into the prevention and treatment of CRC with TCM.
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http://dx.doi.org/10.1177/15347354211017219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145606PMC
May 2021

Targeting histone deacetylase enhances the therapeutic effect of Erastin-induced ferroptosis in -activating mutant lung adenocarcinoma.

Transl Lung Cancer Res 2021 Apr;10(4):1857-1872

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Intrinsic or acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is common, thus strategies for the management of EGFR-TKIs resistance are urgently required. Ferroptosis is a recently discovered form of cell death that has been implicated in tumorigenesis and resistance treatment. Accumulating evidence suggests that ferroptosis can be therapeutically exploited for the treatment of solid tumors; however, whether ferroptosis can be targeted to treat mutant lung cancer and/or overcome the resistance to EGFR-TKIs is still unknown.

Methods: The effect of ferroptosis inducers on a panel of mutant lung cancer cell lines, including those with EGFR-TKI intrinsic and acquired (generated by long-term exposure to the third-generation EGFR-TKI osimertinib), was determined using cytotoxicity assays. Further, drug candidates to enhance the effect of ferroptosis inducers were screened through implementing WGCNA (weighted gene co-expression network analysis) and CMAP (connectivity map) analysis. Flow cytometry-based apoptosis and lipid hydroperoxides measurement were used to evaluate the cell fates after treatment.

Results: Compared with EGFR-TKI-sensitive cells, those with intrinsic or acquired resistance to EGFR-TKI display high sensitivity to ferroptosis inducers. In addition, Vorinostat, a clinically used inhibitor targeting histone deacetylase, can robustly enhance the efficacy of ferroptosis inducers, leading to a dramatic increase of hydroperoxides in mutant lung cancer cells with intrinsic or acquired resistance to EGFR-TKI. Mechanistically, Vorinostat promotes ferroptosis via xCT downregulation.

Conclusions: Ferroptosis-inducing therapy shows promise in -activating mutant lung cancer cells that display intrinsic or acquired resistance to EGFR-TKI. Histone deacetylase inhibitor (HDACi) Vorinostat can further promote ferroptosis by inhibiting xCT expression.
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http://dx.doi.org/10.21037/tlcr-21-303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107764PMC
April 2021

Maternal obesity accelerated non-alcoholic fatty liver disease in offspring mice by reducing autophagy.

Exp Ther Med 2021 Jul 3;22(1):716. Epub 2021 May 3.

Graduate School, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by an excessive accumulation of triacylglycerol in the liver. Autophagy is a lysosome-dependent degradation product recovery process, which widely occurs in eukaryotic cells, responsible for the vital maintenance of cellular energy balance. Previously published studies have demonstrated that autophagy is closely related to NAFLD occurrence and maternal obesity increases the susceptibility of offspring to non-alcoholic fatty liver disease, however, the underlying mechanism of this remains unclear. In the present study, NAFLD mouse models (offspring of an obese mother mouse via high-fat feeding) were generated, and the physiological indices of the liver were observed using total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein serum assay kits. The morphological changes of the liver were also observed via HE, Masson and oil red O staining. Reverse transcription-quantitative-PCR and western blotting were performed to detect changes of autophagy-related genes in liver or fibrosis marker proteins (α-smooth muscle actin or TGF-β). Changes in serum inflammatory cytokine IL-6 levels were determined via ELISA. The results of the present study demonstrated that the offspring of an obese mother were more likely to develop NALFD than the offspring of a chow-fed mother, due to their increased association with liver fibrosis. When feeding continued to 17 weeks, the worst cases of NAFLD were observed and the level of autophagy decreased significantly compared with the offspring of a normal weight mouse. In addition, after 17 weeks of feeding, compared with the offspring of a chow-fed mother, the offspring of an obese mouse mother had reduced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation levels and increased mammalian target of rapamycin (mTOR) phosphorylation levels. These results suggested that a reduced level of AMPK/mTOR mediated autophagy may be of vital importance for the increased susceptibility of offspring to NAFLD caused by maternal obesity. In conclusion, the current study provided a new direction for the treatment of NAFLD in offspring caused by maternal obesity.
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http://dx.doi.org/10.3892/etm.2021.10148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120514PMC
July 2021

Bufalin targets the SRC-3/MIF pathway in chemoresistant cells to regulate M2 macrophage polarization in colorectal cancer.

Cancer Lett 2021 Aug 14;513:63-74. Epub 2021 May 14.

Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China; Shanghai Putuo Central School of Clinical Medicine,Anhui Medicine University, Anhui, 230032, China; Department of General Surgery, Putuo Hospital,Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. Electronic address:

M2-polarized macrophages are one of critical factors in tumour chemoresistance. An increasing number of studies have shown that M2 macrophage polarization can be promoted by chemoresistance. A large number of evidences indicate that Bufalin has significant antitumour effect, previous studies have found that Bufalin can reduce the polarization of M2 macrophages to play an anti-tumour effect in vivo, but the mechanism remains unclear. In our study, we found that Bufalin reduced the polarization of M2 macrophages induced by chemoresistant cells both in vivo and in vitro; however, Bufalin had no obvious direct effect on M2 macrophage polarization. Furthermore, we demonstrated that Bufalin targeted the SRC-3 protein to reduce MIF release in chemoresistant cells in order to regulate the polarization of M2 macrophages. More interestingly, we also found that Cinobufacini, Bufalin is its main active monomer, which its could regulate the polarization of M2 macrophages to enhance the anti-tumour effect of oxaliplatin in vivo and in the clinic. Overall, this study provides a theoretical basis for the clinical application of drugs containing Bufalin as the main active ingredient in combination with established chemotherapy for the treatment of colorectal cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.05.008DOI Listing
August 2021

Cannabinoid Receptor 1 rs1049353 Variant, Childhood Abuse, and the Heterogeneity of PTSD Symptoms: Results From the National Health and Resilience in Veterans Study.

Chronic Stress (Thousand Oaks) 2021 Jan-Dec;5:24705470211011075. Epub 2021 Apr 29.

U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA.

Background: Accumulating evidence implicates the endocannabinoid system, including variants in the cannabinoid-1 receptor gene (), in the pathophysiology of posttraumatic stress disorder (PTSD). The synonymous G1359A variant (rs1049353) in the gene has been linked to PTSD in individuals exposed to childhood abuse. In this study, the effects of the rs1049353 genotype and childhood abuse on overall PTSD symptoms, as well as PTSD symptom clusters were examined in order to examine how this interaction relates to the phenotypic expression of this disorder.

Method: Data were analyzed from 1,372 Caucasian U.S. veterans who participated in the National Health and Resilience in Veterans Study. Multivariable analyses were conducted to evaluate the association between rs1049353 genotype, childhood abuse, and their interaction in relation to PTSD symptoms.

Results: A significant interaction between rs1049353 genotype and childhood abuse was observed, with A allele carriers with histories of childhood abuse reporting greater severity of PTSD symptoms, most notably anxious arousal, relative to G/G homozygotes. Significant main effects of childhood abuse on overall PTSD symptoms, and re-experiencing, emotional numbing, and dysphoric arousal symptom clusters, as well as of A allele carrier status on anxious arousal symptoms were observed.

Conclusions: Results of this study replicate prior work and suggest that the rs1049353-by-childhood abuse interaction is particularly associated with the manifestation of anxious arousal symptoms of PTSD. Taken together, these findings underscore the importance of considering the phenotypic heterogeneity of PTSD in gene-environment studies of this multifaceted disorder.
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http://dx.doi.org/10.1177/24705470211011075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107935PMC
April 2021

What Links Maternal Prepregnancy BMI to Early Childhood BMI: A Serial Mediation Analysis.

Obesity (Silver Spring) 2021 May 14. Epub 2021 May 14.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: The aim of this study was to explore the potential impact of maternal gestational weight gain (GWG), infant birth weight, and postnatal weight change (ΔWAZ) on the relationship between maternal prepregnancy BMI (ppBMI) and childhood BMI.

Methods: This retrospective cohort study analyzed a data set from Wuhan, China. The mediation effect of targeted mediators on the association between maternal BMI and childhood BMI at the age of 2 years was analyzed.

Results: In the mediation model comprising maternal GWG, infant birth weight, and the first-6-month ΔWAZ as mediators of the association between ppBMI and children's BMI, the per unit increase in ppBMI resulted in a 0.01-kg/m increase in children's BMI, through all three mediators. For the model comprising infant birth weight and the first-6-month ΔWAZ as mediators but maternal GWG as a moderator, the indirect effects of the first-6-month ΔWAZ on the relationship between ppBMI and childhood BMI was 0.0018 higher when maternal GWG increased from average values to 1 SD above the average values.

Conclusions: Maternal GWG, infant birth weight, and the first-6-month ΔWAZ mediated the effects of maternal ppBMI on children's BMI. Interventions targeting these factors can mitigate the risk of childhood obesity.
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http://dx.doi.org/10.1002/oby.23176DOI Listing
May 2021

Evolutions of Q-switched mode-locked square noise-like pulse with different cavity lengths.

Appl Opt 2021 May;60(13):3641-3646

A $Q$-switched mode-locked square noise-like pulse (QMLSNLP) is generated in a nonlinear polarization rotation passively mode-locked fiber laser. When the pump power changes from 154 mW to 414 mW, the frequency of the $Q$-switched envelope varies from 21.7 kHz to 38.9 kHz, while the duration of the $Q$-switched envelope decreases from $5.1\,\,{\unicode{x00B5}\rm s}$ to $3.2{\unicode{x00B5}\rm s}$, correspondingly. In the meantime, QMLSNLP keeps the fundamental repetition rate constant, and the pulse duration increases from 3.4 ns to 6.7 ns. By inserting different lengths of single-mode fiber into the ring cavity, the evolutions of QMLSNLP are measured and analyzed. According to the cavity parameters and experimental results, impacts of the cavity length on QMLSNLP are investigated in detail.
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http://dx.doi.org/10.1364/AO.423365DOI Listing
May 2021

Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses.

Immunity 2021 May;54(5):976-987.e7

Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Aerobic glycolysis-the Warburg effect-converts glucose to lactate via the enzyme lactate dehydrogenase A (LDHA) and is a metabolic feature of effector T cells. Cells generate ATP through various mechanisms and Warburg metabolism is comparatively an energy-inefficient glucose catabolism pathway. Here, we examined the effect of ATP generated via aerobic glycolysis in antigen-driven T cell responses. Cd4Ldha mice were resistant to Th17-cell-mediated experimental autoimmune encephalomyelitis and exhibited defective T cell activation, migration, proliferation, and differentiation. LDHA deficiency crippled cellular redox balance and inhibited ATP production, diminishing PI3K-dependent activation of Akt kinase and thereby phosphorylation-mediated inhibition of Foxo1, a transcriptional repressor of T cell activation programs. Th17-cell-specific expression of an Akt-insensitive Foxo1 recapitulated the defects seen in Cd4Ldha mice. Induction of LDHA required PI3K signaling and LDHA deficiency impaired PI3K-catalyzed PIP3 generation. Thus, Warburg metabolism augments glycolytic ATP production, fueling a PI3K-centered positive feedback regulatory circuit that drives effector T cell responses.
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http://dx.doi.org/10.1016/j.immuni.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130647PMC
May 2021

Excitation spectral microscopy for highly multiplexed fluorescence imaging and quantitative biosensing.

Light Sci Appl 2021 May 8;10(1):97. Epub 2021 May 8.

College of Chemistry, University of California, Berkeley, CA, USA.

The multiplexing capability of fluorescence microscopy is severely limited by the broad fluorescence spectral width. Spectral imaging offers potential solutions, yet typical approaches to disperse the local emission spectra notably impede the attainable throughput. Here we show that using a single, fixed fluorescence emission detection band, through frame-synchronized fast scanning of the excitation wavelength from a white lamp via an acousto-optic tunable filter, up to six subcellular targets, labeled by common fluorophores of substantial spectral overlap, can be simultaneously imaged in live cells with low (~1%) crosstalks and high temporal resolutions (down to ~10 ms). The demonstrated capability to quantify the abundances of different fluorophores in the same sample through unmixing the excitation spectra next enables us to devise novel, quantitative imaging schemes for both bi-state and Förster resonance energy transfer fluorescent biosensors in live cells. We thus achieve high sensitivities and spatiotemporal resolutions in quantifying the mitochondrial matrix pH and intracellular macromolecular crowding, and further demonstrate, for the first time, the multiplexing of absolute pH imaging with three additional target organelles/proteins to elucidate the complex, Parkin-mediated mitophagy pathway. Together, excitation spectral microscopy provides exceptional opportunities for highly multiplexed fluorescence imaging. The prospect of acquiring fast spectral images without the need for fluorescence dispersion or care for the spectral response of the detector offers tremendous potential.
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http://dx.doi.org/10.1038/s41377-021-00536-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105378PMC
May 2021

MicroRNA-29b/29c targeting CTRP6 influences porcine adipogenesis via the AKT/PKA/MAPK Signalling pathway.

Adipocyte 2021 Dec;10(1):264-274

Key Laboratory of Animal Nutrition & Feed Sciences, College of Animal Sciences, Zhejiang University, Hangzhou, China.

Porcine fat deposition is an important economic trait of pig breeds, and understanding the gene regulatory network in adipocytes is essential for modern pig breeding. In a previous study, we demonstrated that miR-29a negatively regulates the differentiation of porcine adipocytes. In this study, we investigated the roles of miR-29b/c in porcine adipocytes and the underlying mechanisms. Using EdU staining and the CCK-8 assay, we observed that transfection with the miR-29b/c agomir promoted the proliferation of porcine intramuscular (IM) and subcutaneous (SC) adipocytes by altering the expression of cell-cycle-related genes. According to the results of oil red O staining and western blot analysis, transfection with the miR-29b/c agomir suppressed the differentiation of porcine SC and IM adipocytes via the AKT/PKA/MAPK signalling pathway. Furthermore, we proved that miR-29b/c regulates porcine adipocytes by directly targeting the 3'-untranslated region (3'UTR) of CTRP6 using a dual-luciferase reporter assay. Finally, co-transfection with miR-29b/c and CTRP6 partially restored the changes of phenotype and gene expression induced by miR-29b/c overexpression in 3T3-L1 adipocytes. Taken together, our data demonstrate that both miR-29b and miR-29 c negatively regulate porcine adipogenesis by targeting CTRP6, which furthers our understanding of the gene network that regulates fat deposition in pigs.
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http://dx.doi.org/10.1080/21623945.2021.1917811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096332PMC
December 2021

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

Pancreatology 2021 Apr 22. Epub 2021 Apr 22.

State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Purpose: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT).

Patients And Methods: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated.

Results: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458).

Conclusion: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.
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http://dx.doi.org/10.1016/j.pan.2021.04.007DOI Listing
April 2021

Vertebrate cells differentially interpret ciliary and extraciliary cAMP.

Cell 2021 May 30;184(11):2911-2926.e18. Epub 2021 Apr 30.

Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA 94158, USA. Electronic address:

Hedgehog pathway components and select G protein-coupled receptors (GPCRs) localize to the primary cilium, an organelle specialized for signal transduction. We investigated whether cells distinguish between ciliary and extraciliary GPCR signaling. To test whether ciliary and extraciliary cyclic AMP (cAMP) convey different information, we engineered optogenetic and chemogenetic tools to control the subcellular site of cAMP generation. Generating equal amounts of ciliary and cytoplasmic cAMP in zebrafish and mammalian cells revealed that ciliary cAMP, but not cytoplasmic cAMP, inhibited Hedgehog signaling. Modeling suggested that the distinct geometries of the cilium and cell body differentially activate local effectors. The search for effectors identified a ciliary pool of protein kinase A (PKA). Blocking the function of ciliary PKA, but not extraciliary PKA, activated Hedgehog signal transduction and reversed the effects of ciliary cAMP. Therefore, cells distinguish ciliary and extraciliary cAMP using functionally and spatially distinct pools of PKA, and different subcellular pools of cAMP convey different information.
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http://dx.doi.org/10.1016/j.cell.2021.04.002DOI Listing
May 2021

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis.

J Exp Clin Cancer Res 2021 Apr 30;40(1):150. Epub 2021 Apr 30.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing, 400016, Yuzhong District, China.

Background: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment.

Methods: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo.

Results: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200.

Conclusion: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.
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http://dx.doi.org/10.1186/s13046-021-01948-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086320PMC
April 2021

Smaller volume and altered functional connectivity of the amygdala in patients with lifelong premature ejaculation.

Eur Radiol 2021 Apr 30. Epub 2021 Apr 30.

Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, 710071, Shaanxi, China.

Objectives: To analyze the abnormal amygdala structure and function in lifelong premature ejaculation (PE) patients compared with healthy controls (HCs).

Methods: Forty-four lifelong PE patients and thirty-one HCs were enrolled in this study. Each subject was diagnosed with PE using a Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) score. Based on t-tests and Pearson correlation analysis, the voxel-based morphometry and functional connectivity (FC) analyses were applied to evaluate brain structural and functional changes by using T1-weighted and resting-state functional magnetic resonance imaging scans.

Results: Lifelong PE patients had decreased gray matter volume in the bilateral amygdala and increased FC between the amygdala and precuneus, posterior cingulate cortex (PCC), and middle temporal cortex (MTC), as well as decreased FC between the amygdala and precentral gyrus, insula, and inferior frontal gyrus. Moreover, significantly negative correlations between the IELT score and the mean z-score from amygdala-MTC (r = -0.49) and amygdala-PCC (r = -0.48) FC were found in lifelong PE patients.

Conclusions: Our study investigated the abnormal amygdala-related structure and connectivity patterns in PE patients, which might provide novel perspective for understanding the crucial role of the amygdala in the neural mechanism of PE.

Key Points: • As one of the most common diseases in men, PE may be related to abnormal brain mechanisms. • Functional and structural magnetic resonance imaging used to explore amygdala abnormalities in PE patients. • The correlation between clinical scores and functional connectivity was used to assess the reasonability of the results.
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http://dx.doi.org/10.1007/s00330-021-08002-9DOI Listing
April 2021

A Numerical Model for Simulating the Hemodynamic Effects of Enhanced External Counterpulsation on Coronary Arteries.

Front Physiol 2021 12;12:656224. Epub 2021 Apr 12.

Department of Biomedical Engineering, Beijing University of Technology, Beijing, China.

Traditional enhanced external counterpulsation (EECP) used for the clinical treatment of patients with coronary heart disease only assesses diastolic/systolic blood pressure (Q = D/S > 1.2). However, improvement of the hemodynamic environment surrounding vascular endothelial cells of coronary arteries after long-term application of EECP is the basis of the treatment. Currently, the quantitative hemodynamic mechanism is not well understood. In this study, a standard 0D/3D geometric multi-scale model of the coronary artery was established to simulate the hemodynamic effects of different counterpulsation modes on the vascular endothelium. In this model, the neural regulation caused by counterpulsation was thoroughly considered. Two clinical trials were carried out to verify the numerical calculation model. The results demonstrated that the increase in counterpulsation pressure amplitude and pressurization duration increased coronary blood perfusion and wall shear stress (WSS) and reduced the oscillatory shear index (OSI) of the vascular wall. However, the impact of pressurization duration was the predominant factor. The results of the standard model and the two real individual models indicated that a long pressurization duration would cause more hemodynamic risk areas by resulting in excessive WSS, which could not be reflected by the change in the Q value. Therefore, long-term pressurization during each cardiac cycle therapy is not recommended for patients with coronary heart disease and clinical treatment should not just pay attention to the change in the Q value. Additional physiological indicators can be used to evaluate the effects of counterpulsation treatment.
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http://dx.doi.org/10.3389/fphys.2021.656224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072480PMC
April 2021

Corrigendum: Vitamin B12 Enhances Nerve Repair and Improves Functional Recovery After Traumatic Brain Injury by Inhibiting ER Stress-Induced Neuron Injury.

Front Pharmacol 2021 12;12:598335. Epub 2021 Apr 12.

Department of Emergency, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.

[This corrects the article DOI: 10.3389/fphar.2019.00406.].
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http://dx.doi.org/10.3389/fphar.2021.598335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075574PMC
April 2021

Identification of an Invertase With High Specific Activity for Raffinose Hydrolysis and Its Application in Soymilk Treatment.

Front Microbiol 2021 8;12:646801. Epub 2021 Apr 8.

School of Life Sciences, Anhui University, Hefei, China.

The hydrolyzation of raffinose into melibiose by using invertases under mild conditions improves the nutritional value of soybean products. However, this strategy has received little attention because a suitable invertase remains lacking. In this study, a novel invertase named InvDz13 was screened and purified from and characterized. InvDz13 was one of the invertases with the highest specific activity toward raffinose. Specifically, it had a specific activity of 229 U/mg toward raffinose at pH 6.5 and 35°C. InvDz13 retained more than 80% of its maximum activity at pH 5.5-7.5 and 25-40°C and was resistant to or stimulated by most cations that presented in soymilk. In soymilk treated with InvDz13 under mild conditions, melibiose concentration increased from 3.1 ± 0.2 to 6.1 ± 0.1 mM due to raffinose hydrolyzation by InvDz13. Furthermore, the prebiotic property of InvDz13-treated soymilk was investigated via fermentation by human gut microbiota. Results showed that InvDz13 treatment increased the proportion of the beneficial bacteria and by 1.6- and 3.7-fold, respectively. By contrast, the populations of and decreased by 1.8- and 11.7-fold, respectively. Thus, our results proved that the enzymatic hydrolysis of raffinose in soymilk with InvDz13 was practicable and might be an alternative approach to improving the nutritional value of soymilk.
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http://dx.doi.org/10.3389/fmicb.2021.646801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060482PMC
April 2021

Effect of combination invasive intracranial pressure (ICP) monitoring and transcranial Doppler in the treatment of severe craniocerebral injury patients with decompressive craniectomy.

Ann Palliat Med 2021 Apr 14;10(4):4472-4478. Epub 2021 Apr 14.

Department of Neurosurgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China.

Background: The aim of the present study was to explore the clinical effect and to predict the prognosis of severe craniocerebral injury patients with decompressive craniectomy by combining transcranial Doppler (TCD) and invasive intracranial pressure (ICP).

Methods: A total of 60 severe craniocerebral injury patients with decompressive craniectomy, who were admitted to Shantou Central Hospital from June 2017 to March 2019, were enrolled in this retrospective study. Of these, 25 patients who had a Glasgow Coma Scale (GCS) score no greater 8 and no less than 6 underwent transcranial Doppler (TCD) before decompressive craniectomy, as well as ICP, after removing the skull and suturing the dura mater. The 60 patients were divided into 2 groups according to the following standards: (I) GCS score ≥8 on the 7th day postoperatively; (II) ICP continuously lower than 25 mmHg for the entire 7-day duration postoperatively; and (III) brain tissue consistently offset from the skull surface by 5 mm. The clinical outcome was determined based on the Glasgow Outcome Scale (GOS) 1, 3, and 6 months postoperatively. The TCD value, ICP, and prognosis were compared between the 2 groups.

Results: The average postoperative ICP <19 mmHg in the first 24 h, mean blood flow velocity >56.33 cm/s, end-diastolic blood flow velocity >40.28 cm/s, and resistance index <0.57 were statistically significant indicators to predict good prognosis .

Conclusions: The use of TCD can predict the prognosis of severe craniocerebral injury patients.
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http://dx.doi.org/10.21037/apm-21-504DOI Listing
April 2021